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Sample records for 111in ibritumomab tiuxetan

  1. Unsuspected pneumonia detected by increased lung uptake on 111In-ibritumomab tiuxetan scan.

    PubMed

    Hwang, Misun; Joyce, Judith M; Klein, Herbert; Hou, Jing-Zhou

    2012-10-01

    99Y-ibritumomab tiuxetan (Zevalin) is a CD20-targeted radioimmunotherapy for the treatment of B-cell non-Hodgkin lymphoma approved by the FDA in 2002. The acquisition of an 111In ibritumomab tiuxetan scan (bioscan) to confirm normal biodistribution before treatment with 99Y-ibritumomab tiuxetan was initially required in the United States until November 2011. This is the first documented example of abnormal biodistribution due to unsuspected pneumonia detected by increased lung uptake on the bioscan. The pneumonia was treated and resolved before 99Y Zevalin, avoiding potential harm and indicating that a screening chest x-ray may be appropriate when a bioscan is not performed. PMID:22955077

  2. Imaging and dosing in radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin).

    PubMed

    Spies, Stewart M

    2004-01-01

    Yttrium 90 ibritumomab tiuxetan consists of the murine monoclonal antibody ibritumomab securely bound to the second-generation chelator tiuxetan, which attaches the high-energy pure beta emitter (90)Y, for therapy, or the gamma emitter indium 111, for imaging. The biodistribution of the therapeutic dose of (90)Y ibritumomab tiuxetan can be predicted by using an imaging dose of the antibody labeled with (111)In. Calculation of the therapeutic dose is simple and is based on patient weight and baseline platelet count: for patients with a platelet count of 150 x 10(9)/L or greater the dose of is 0.4 mCi/kg; for patients with mild thrombocytopenia (platelet count 100 x 10(9)/L to 149 x 10(9)/L) the dose is reduced to 0.3 mCi/kg; and the total dose should not exceed 32 mCi. Patients with platelet counts of less than 100 x 10(9)/L should not be treated with (90)Y ibritumomab tiuxetan. Imaging with (111)In ibritumomab tiuxetan is performed only to assess biodistribution of the radioimmunoconjugate. Uptake in sites of pathologic adenopathy, as well as other areas of lymphomatous involvement, is frequently seen on the images, but visualization of tumor uptake is not required to proceed with the therapeutic dose of (90)Y ibritumomab tiuxetan. PMID:14762739

  3. Selecting patients for treatment with 90Y ibritumomab tiuxetan (Zevalin).

    PubMed

    Gregory, Stephanie A

    2003-12-01

    Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first radioimmunotherapeutic agent approved by the US Food and Drug Administration. It is indicated for treating patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with rituximab-refractory follicular non-Hodgkin's lymphoma. Proper patient selection is essential for optimizing the efficacy and safety of treatment with (90)Y ibritumomab tiuxetan. It may be advisable to use (90)Y ibritumomab tiuxetan relatively early in a patient's course of treatment because overall and complete response rates, and the estimated median duration of response, are higher among patients who have had fewer median prior antineoplastic regimens than among those who have had a greater median number of such regimens. Furthermore, the myeloablative effect of multiple courses of chemotherapy can preclude the later use of (90)Y ibritumomab tiuxetan. In contrast, other therapies, including chemotherapy and rituximab, can be used safely and successfully after (90)Y ibritumomab tiuxetan without concerns about increased hematologic toxicity from the previous radioimmunotherapy. The main adverse event associated with (90)Y ibritumomab tiuxetan therapy is hematologic toxicity and, as a result, only patients with adequate bone marrow reserves and less than 25% lymphoma marrow involvement should currently be considered for clinical therapy. PMID:14710399

  4. Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma.

    PubMed

    Witzig, Thomas E

    2004-02-01

    This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. Since yttrium-90 ((90)Y) is a pure beta emitter and cannot be used for patient imaging, indium-111 ((111)In) is chelated to ibritumomab tiuxetan for tumor and normal organ imaging in clinical practice and for dosimetry in clinical trials. (90)Y-ibritumomab tiuxetan is the form used for therapy. This review discusses the clinical trials that have demonstrated the efficacy of ibritumomab tiuxetan and summarizes the safety data in patients with relapsed B-cell non-Hodgkin's lymphomas. Two phase I trials of (90)Y-ibritumomab tiuxetan were conducted to establish the toxicity profile and the maximum tolerated single dose that could be administered to outpatients without the use of stem cells or prophylactic growth factors. In the first trial, cold ibritumomab was used prior to ibritumomab tiuxetan; the second trial used the human chimeric antibody rituximab. The phase I trials determined that in patients with a platelet count of greater than or equal to 150 x 10(9)/l, a schedule of intravenous rituximab 250 mg/m(2) on days 1 and 8, and 0.4 mCi/ kg of intravenous (90)Y-ibritumomab tiuxetan on day 8 was safe and efficacious and did not require stem cells. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000- 149,000 x 10(6)/l. Adverse events were primarily hematologic, and nonhematologic adverse events were primarily due to rituximab. There was no normal organ toxicity. The overall response rate was 67% for all patients and 82% in patients with low-grade non-Hodgkin's lymphomas. A subsequent phase III trial randomized 143 eligible patients to

  5. Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin's lymphoma.

    PubMed

    Micallef, Ivana N M

    2004-10-01

    Targeted radiation therapy or radioimmunotherapy has been an important recent advance in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan, and the radiolabeled isotope yttrium 90. Yttrium 90 ibritumomab tiuxetan has been shown to be efficacious in the treatment of B-cell NHL. Initial phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and dose intensities in combination with chemotherapy and autologous or allogeneic stem cell transplantation in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas including mantle cell lymphoma, and chronic lymphocytic leukemia. This article reviews the ongoing trials with 90Y ibritumomab tiuxetan. Radioimmunotherapy has great promise, and the safe incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL. PMID:15498147

  6. Testis dosimetry in individual patients by combining a small-scale dosimetry model and pharmacokinetic modeling-application of 111In-Ibritumomab Tiuxetan (Zevalin®)

    NASA Astrophysics Data System (ADS)

    Meerkhan, Suaad A.; Sjögreen-Gleisner, Katarina; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

    2014-12-01

    A heterogeneous distribution of radionuclides emitting low-energy electrons in the testicles may result in a significant difference between an absorbed dose to the radiosensitive spermatogonia and the mean absorbed dose to the whole testis. This study focused on absorbed dose distribution in patients at a finer scale than normally available in clinical dosimetry, which was accomplished by combining a small-scale dosimetry model with patient pharmacokinetic data. The activity in the testes was measured and blood sampling was performed for patients that underwent pre-therapy imaging with 111In-Zevalin®. Using compartment modeling, testicular activity was separated into two components: vascular and extravascular. The uncertainty of absorbed dose due to geometry variations between testicles was explored by an assumed activity micro-distribution and by varying the radius of the interstitial tubule. Results showed that the absorbed dose to germ cells might be strongly dependent on the location of the radioactive source, and may exceed the absorbed dose to the whole testis by as much as a factor of two. Small-scale dosimetry combined with compartmental analysis of clinical data proved useful for gauging tissue dosimetry and interpreting how intrinsic geometric variation influences the absorbed dose.

  7. Use of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma.

    PubMed

    Marcus, Robert

    2005-02-01

    The increase in the incidence of non-Hodgkin's lymphoma (NHL) that has occurred over recent decades is expected to continue. Therapeutic options for patients with NHL have improved over the past 20 years, but almost all patients with low-grade lymphoma and approximately 50% of patients with high-grade lymphoma eventually die of their disease, regardless of the regimen used. Thus, there is a continuing need for novel therapeutic options. One such strategy is targeted radioimmunotherapy, which is an attractive approach because lymphoma cells are inherently sensitive to radiation. 90 Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) was the first radioimmunotherapy agent to be approved by the US Food and Drug Administration for the treatment of patients with relapsed, low-grade B-cell NHL. 90Y-ibritumomab tiuxetan comprises the murine IgG1 anti-CD20 antibody ibritumomab, covalently linked to the beta-emitter 90 Y by a chelator tiuxetan. A prospective trial comparing 90Y-ibritumomab tiuxetan with single-agent rituximab showed an overall response rate (ORR) to 90Y-ibritumomab tiuxetan of 80% (34% complete response [CR]/unconfirmed CR [CRu]) compared with 56% (20% CR/CRu) with rituximab (P = .002). Of patients achieving a CR/CRu, 32% were still in remission at 3 to 4 years of follow-up. Similar efficacy (83% ORR, 43% CR/CRu) has been reported with 90 Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade NHL with mild thrombocytopenia (platelet counts 100,000 to 149,000/mm3 ), and in patients with rituximab-refractory NHL (ORR 74% [CR 15%] compared with an ORR 32% to last rituximab treatment). Safety data compiled from patients entered into five studies have confirmed initial observations that the toxicities encountered with 90Y-ibritumomab tiuxetan therapy are mainly hematologic and transient. As part of a consolidated clinical approach to the ongoing development of 90Y-ibritumomab tiuxetan, studies are

  8. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunity

    PubMed Central

    Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

    2016-01-01

    Y-ibritumomab tiuxetan (90Y-IT) combines the benefits of a monoclonal antibody with the efficacy of radiation in the treatment of B-cell non-Hodgkin lymphoma (NHL), a remarkably radiosensitive hematologic malignancy. 90Y-IT activity has been well established in the indolent setting, being approved in front-line treatment of follicular lymphoma (FL) patients as well as salvage therapy. However, no advantage in OS was observed with respect to standard treatment. Promising data are available also for aggressive B-cell lymphoma. In particular, the addition of RIT to short-course first line chemotherapy enables reduction of chemotherapy while maintaining cure rates in elderly, untreated diffuse large B-cell lymphoma (DLBCL) patients. Furthermore, 90Y-IT improves response rate and outcomes of relapsed/refractory DLBCL patients, eligible and ineligible for autologous stem cell transplantation (ASCT). Clinical results have shown a role of 90Y-IT even in mantle cell lymphoma (MCL). RIT might improve responses and treat minimal residual disease when used as consolidation after first-line chemotherapy in MCL. Moreover, 90Y-IT has demonstrated its efficacy in combination with high-dose chemotherapies as conditioning regimen for ASCT, with evidence suggesting the ability to overcome chemotherapy resistance. Herein, we review the available evidence for this approved drug and examine the recently published and ongoing trials for potential novel indication in aggressive B-cell NHL. PMID:26657116

  9. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunityr.

    PubMed

    Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

    2016-02-16

    Y-ibritumomab tiuxetan (90Y-IT) combines the benefits of a monoclonal antibody with the efficacy of radiation in the treatment of B-cell non-Hodgkin lymphoma (NHL), a remarkably radiosensitive hematologic malignancy. 90Y-IT activity has been well established in the indolent setting, being approved in front-line treatment of follicular lymphoma (FL) patients as well as salvage therapy. However, no advantage in OS was observed with respect to standard treatment. Promising data are available also for aggressive B-cell lymphoma. In particular, the addition of RIT to short-course first line chemotherapy enables reduction of chemotherapy while maintaining cure rates in elderly, untreated diffuse large B-cell lymphoma (DLBCL) patients. Furthermore, 90Y-IT improves response rate and outcomes of relapsed/refractory DLBCL patients, eligible and ineligible for autologous stem cell transplantation (ASCT). Clinical results have shown a role of 90Y-IT even in mantle cell lymphoma (MCL). RIT might improve responses and treat minimal residual disease when used as consolidation after first-line chemotherapy in MCL. Moreover, 90Y-IT has demonstrated its efficacy in combination with high-dose chemotherapies as conditioning regimen for ASCT, with evidence suggesting the ability to overcome chemotherapy resistance. Herein, we review the available evidence for this approved drug and examine the recently published and ongoing trials for potential novel indication in aggressive B-cell NHL. PMID:26657116

  10. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial.

    PubMed

    Wiseman, Gregory A; Gordon, Leo I; Multani, Pratik S; Witzig, Thomas E; Spies, Stewart; Bartlett, Nancy L; Schilder, Russell J; Murray, James L; Saleh, Mansoor; Allen, Roberta S; Grillo-López, Antonio J; White, Christine A

    2002-06-15

    Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population. PMID:12036859

  11. Efficacy and safety of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy for non-Hodgkin's lymphoma.

    PubMed

    Witzig, Thomas E

    2003-12-01

    Radioimmunotherapy, an emerging treatment option for certain patients with non-Hodgkin's lymphoma (NHL), enables the targeting of cytotoxic radiation to tumor cells with minimal irradiation of normal cells. Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was approved in February 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory NHL. Yttrium 90 ibritumomab tiuxetan is an effective treatment with a consistent overall response rate of 73% to 83%. It has a good safety profile and is generally well tolerated in the indicated population. The results of clinical trials show that (90)Y ibritumomab tiuxetan can be used effectively and safely in many patients with NHL, including those with mild thrombocytopenia and those with disease that is refractory to rituximab, without the adverse events associated with conventional chemotherapy and external beam radiation therapy. The use of (90)Y ibritumomab tiuxetan does not preclude subsequent therapy with other conventional treatment options. PMID:14710398

  12. Retreatment with yttrium-90 ibritumomab tiuxetan in patients with B-cell non-Hodgkin's lymphoma.

    PubMed

    Shah, Jatin; Wang, Wenquan; Harrough, V Douglas; Saville, Wayne; Meredith, Ruby; Shen, Sui; Mueh, John; Lister, John; Jasthy, Sri; Maggass, Gregory; McKay, Charles; Krumdieck, Richard; Tharp, Morgan; Winter, Christine; Gregory, Stephanie; Buchholz, William; Awasthi, Sanjay; Jacobs, Samuel; Chung, Harold; Egner, James; Lobuglio, Albert F; Forero, Andres

    2007-09-01

    There is no data on safety and efficacy of a second course of ibritumomab tiuxetan. In this work, data on patients with B-cell NHL who were treated with two courses of ibritumomab tiuxetan were analyzed. Eighteen such patients were analyzed (age: 58 years, 48 - 91), with a median of four prior regimens (1 - 7), stem cell transplantation (n = 5), and radiation therapy (n = 6). After the first course, G3/4 neutropenia and thrombocytopenia was 35% and 41%; overall response rate (ORR) was 89%; time between courses was 16.6 months (6.0 - 42.7). After the second course, the incidence of G3/4 neutropenia and thrombocytopenia was 28% and 44%; and ORR 77%. There were no infectious or bleeding complications, secondary myelodysplastic syndromes, or leukemias. Retreatment with the ibritumomab tiuxetan regimen was well tolerated, with a safety profile similar to that of the first course. To conclude, patients who benefited from the first course of ibritumomab tiuxetan can benefit from retreatment. PMID:17786709

  13. Radiation dosimetry results from a Phase II trial of ibritumomab tiuxetan (Zevalin) radioimmunotherapy for patients with non-Hodgkin's lymphoma and mild thrombocytopenia.

    PubMed

    Wiseman, Gregory A; Leigh, Bryan R; Erwin, William D; Sparks, Richard B; Podoloff, Donald A; Schilder, Russell J; Bartlett, Nancy L; Spies, Stewart M; Grillo-López, Antonio J; Witzig, Thomas E; White, Christine A

    2003-04-01

    This was a 30-patient Phase II trial of reduced-dose (90)Y ibritumomab tiuxetan (Zevalin) RIT for patients with low-grade, follicular, or transformed B-cell NHL and mild thrombocytopenia. Patients were given an imaging dose of (111)In-labeled ibritumomab tiuxetan for dosimetry measurements. One week later, patients were administered a therapeutic dose of 0.3 mCi/kg (11 MBq/kg) (90)Y ibritumomab tiuxetan. Both (111)In- and (90)Y-labeled ibritumomab tiuxetan doses were preceded by an infusion of 250 mg/m(2) rituximab (Rituxan, MabThera) an unlabeled chimeric anti-CD20 antibody, to clear peripheral blood B cells and improve biodistribution of the radiolabeled antibody. For all 30 patients, normal organ and red marrow radiation absorbed doses were well below protocol-defined limits of 2000 cGy and 300 cGy, respectively. Median radiation absorbed doses were 48 cGy to red marrow (range: 6.5-95 cGy), 393 cGy to liver (range: 92-1581 cGy), 522 cGy to spleen (range: 165-1711 cGy), 162 cGy to lungs (41-295 cGy), and 14 cGy to kidneys (0.03-65 cGy). Though most correlative analyses were negative, certain analyses demonstrated a statistically significant correlation between the severity or duration of thrombocytopenia and pharmacokinetic or dosimetric parameters. These correlations were not consistent across the total patient population, and therefore, could not be exploited to predict hematologic toxicity. PMID:12804042

  14. [Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives].

    PubMed

    Schomäcker, K; Dietlein, M; Schnell, R; Pinkert, J; Eschner, W; Zimmermanns, B; Fischer, T; Engert, A; Schicha, H

    2005-01-01

    90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval. PMID:16163413

  15. Zevalin(®) (ibritumomab tiuxetan): After more than a decade of treatment experience, what have we learned?

    PubMed

    Rizzieri, David

    2016-09-01

    Non-Hodgkin's lymphoma (NHL) comprises a clinically and biologically heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer (NK) cells. The disease course may range from indolent to aggressive. Zevalin(®) (ibritumomab tiuxetan) is a radioactive drug product, which is the combination of a β-emitting isotope, (90)Y, linked to the anti-CD20 monoclonal antibody (mAb), rituximab. It has demonstrated therapeutic efficacy with durable responses and allows delivery of ionizing radiation directly to the tumor site, while minimizing toxicity to normal tissue. Ibritumomab tiuxetan is indicated for treatment of patients with relapsed or refractory low-grade, follicular NHL, including patients who are refractory to rituximab, and as consolidation therapy in previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy. Despite the efficacy and acceptable safety profile of ibritumomab tiuxetan, utilization has not been broadly adopted in practice due to a number of factors. This manuscript will review the literature available for ibritumomab tiuxetan, including several new trials that are currently being studied, and discuss the rationale for use of ibritumomab tiuxetan in NHL. PMID:27497027

  16. p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

    SciTech Connect

    Su, Hang; Ganapathy, Suthakar; Li, Xiaolei; Yuan, Zhi-Min; Ha, Chul S.

    2015-08-01

    Purpose: The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Methods and Materials: Mice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to examine morphology, DNA damage response, and apoptotic cell populations. Results: Elevated levels of NFκB, Glut1, and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damage levels induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA

  17. P53-Based Strategy for Protection of Bone Marrow from Y-90 Ibritumomab Tiuxetan

    PubMed Central

    Su, Hang; Ganapathy, Suthakar; Li, Xiaolei; Yuan, Zhi-Min; Ha, Chul S.

    2015-01-01

    Purpose The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. p53 activation is a major pathway by which normal tissues respond to DNA damaging agents such as chemotherapy and radiotherapy, resulting in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that the use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from 5-FU and X-ray. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here, we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Method and Materials Mice were subject to LDA pretreatment for three days, followed by Y-90 ibritumomab tiuxetan treatment. Both dose-course (10, 25, 50, 100 and 200 μCi) and time-course (6h, 24h, 72h, 1wk and 2wk) experiments were performed. The response of bone marrow cells to LDA was examined by examining the expression of NFκB, Glut1 and Glut3. H&E, γ-H2AX, and TUNEL staining was employed to examine morphology, DNA damage response and apoptotic cell populations. Results Elevated levels of NFκB, Glut1 and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damages induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression. Conclusions

  18. Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

    PubMed

    Ibatici, Adalberto; Pica, Gian Matteo; Nati, Sandro; Vitolo, Umberto; Botto, Barbara; Ciochetto, Chiara; Petrini, Mario; Galimberti, Sara; Ciabatti, Elena; Orciuolo, Enrico; Zinzani, Pier Luigi; Cascavilla, Nicola; Guolo, Fabio; Fraternali Orcioni, Giulio; Carella, Angelo M

    2014-03-01

    (90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL. PMID:24344981

  19. 90Yttrium Ibritumomab Tiuxetan Therapy in Allogeneic Transplantation in B-cell Lymphoma with Extensive Marrow involvement and Chronic Lymphocytic Leukemia: Utility of Pre-transplantation Biodistribution

    PubMed Central

    Matesan, Manuela; Rajendran, Joseph; Press, Oliver W.; Maloney, David G.; Storb, Rainer F.; Cassaday, Ryan D.; Pagel, John M.; Oliveira, George; Gopal, Ajay K.

    2014-01-01

    Biodistribution data to-date using 111In- ibritumomab tiuxetan has been initially obtained in patients with <25% lymphomatous bone marrow involvement and adequate hematopoietic synthetic function. In this article we present the results of an analysis of the biodistribution data obtained from a cohort of patients with extensive bone marrow involvement, baseline cytopenias, and chronic lymphocytic leukemia (CLL). Thirty nine patients with diagnosis of B-cell lymphoma or CLL expressing the CD20 antigen, who had failed at least one prior regimen, and had evidence of persistent disease were included in this analysis, however only 38 of these completed the treatment. Semiquantitative analysis of the biodistribution was performed using regions of interest (ROI) over the liver, lungs, kidneys, spleen and sacrum. The observed interpatient variability including higher liver uptake in 4 patients is discussed. No severe solid organs toxicity was observed at the maximum administered activity of 1184 MBq (32 mCi) 90Yibritumomab tiuxetan. After accounting for differences in marrow involvement, patients with CLL exhibit comparable biodistributions to those with B-NHL. We found that the estimated sacral marrow uptake on 48 hour images in patients with bone marrow involvement may be an indicator of bone marrow involvement. There was no correlation between tumor visualization and response to treatment. These data suggest that the imaging step is not critical when the administered activity is below 1184 MBq (32 mCi). However our analysis confirms that the semiquantitative imaging data can be used to identify patients at risk for liver toxicity when higher doses of 90Y- ibritumomab tiuxetan are used. Patients with CLL can have excellent targeting of disease by 111Inibritumomab tiuxetan, indicating potential efficacy in this patient population. PMID:25076159

  20. Antilymphoma treatments given subsequent to Yttrium 90 ibritumomab tiuxetan are feasible in patients with progressive non-Hodgkin's lymphoma: a review of the literature.

    PubMed

    Ansell, Stephen M; Schilder, Russell J; Pieslor, Peter C; Gordon, Leo I; Emmanouilides, Christos; Vo, Katie; Czuczman, Myron S; Witzig, Thomas E; Theuer, Charles; Molina, Arturo

    2004-12-01

    Yttrium 90-labeled ibritumomab tiuxetan is approved for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). To date, the efficacy of repeated courses of radioimmunoconjugate treatment in patients whose disease has progressed has not been studied as a formal endpoint in a clinical trial setting. However, several clinical studies have been conducted in patients with progressive NHL who had previously received 90Y ibritumomab tiuxetan. A retrospective review of these studies has shown that clinical responses have been achieved with all types of subsequent treatment with no apparent impact on their efficacy. In addition, no significant differences in toxicities with subsequent therapies have been observed between patients who had previously received 90Y ibritumomab tiuxetan therapy and those who had not. These findings suggest that patients previously treated with 90Y ibritumomab tiuxetan can feasibly undergo other forms of treatment for progressive NHL, and that a clinical response to further treatment options is not precluded by administration of 90Y ibritumomab tiuxetan. PMID:15636698

  1. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma

    PubMed Central

    Nademanee, Auayporn; Forman, Stephen; Molina, Arturo; Fung, Henry; Smith, David; Dagis, Andy; Kwok, Cheuk; Yamauchi, Dave; Anderson, Anne-Line; Falk, Peter; Krishnan, Amrita; Kirschbaum, Mark; Kogut, Neil; Nakamura, Ryotaro; O'Donnell, Margaret; Parker, Pablo; Popplewell, Leslie; Pullarkat, Vinod; Rodriguez, Roberto; Sahebi, Firoozeh; Smith, Eileen; Snyder, David; Stein, Anthony; Spielberger, Ricardo; Zain, Jasmine; White, Christine; Raubitschek, Andrew

    2005-01-01

    We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/μL and platelet count more than 20 000/μL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment. (Blood. 2005;106:2896-2902) PMID:16002426

  2. Current status and future perspectives for yttrium-90 ((90)Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin's lymphoma.

    PubMed

    Gisselbrecht, C; Bethge, W; Duarte, R F; Gianni, A M; Glass, B; Haioun, C; Martinelli, G; Nagler, A; Pettengell, R; Sureda, A; Tilly, H; Wilson, K

    2007-12-01

    Haematopoietic SCT is currently considered a therapeutic option mainly in relapsed or refractory non-Hodgkin's lymphoma (NHL) owing to high post-transplantation relapse rates and significant toxicity of conventional myeloablative conditioning for allogeneic SCT. Radiolabelled immunotherapy combines the benefits of monoclonal antibody targeting with therapeutic doses of radiation, and is a promising advance in the treatment of malignant lymphomas. It is now under investigation as a component of conditioning prior to SCT, with the aim of improving outcomes following SCT without increasing the toxicity of high-dose chemotherapy pre-transplant conditioning. An expert panel met at a European workshop in November 2006 to review the latest data on radiolabelled immunotherapy in the transplant setting, and its potential future directions, with a focus on (90)Y-ibritumomab tiuxetan. They reviewed data on the combination of standard/high/escalating dose (90)Y-ibritumomab tiuxetan with high-dose chemotherapy, and high/escalating dose (90)Y-ibritumomab tiuxetan as the sole myeloablative agent, prior to autologous SCT, and also (90)Y-ibritumomab tiuxetan as a component of reduced intensity conditioning prior to allogeneic SCT. The preliminary data are highly promising in terms of conditioning tolerability and patient outcomes following transplant; further phase II studies are now needed to consolidate these data and to investigate specific patient populations and NHL subtypes. PMID:17922042

  3. Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma

    PubMed Central

    Sánchez Ruiz, Antonio C.; de la Cruz-Merino, Luis

    2014-01-01

    Non-Hodgkin’s lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. 90Y-ibritumomab tiuxetan (90Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with 90Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. 90Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS. PMID:24883180

  4. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma.

    PubMed

    Lossos, Izidore S; Fabregas, Jesus C; Koru-Sengul, Tulay; Miao, Feng; Goodman, Deborah; Serafini, Aldo N; Hosein, Peter J; Stefanovic, Alexandra; Rosenblatt, Joseph D; Hoffman, James E

    2015-06-01

    The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with (90)yttrium ((90)Y) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [CI]: 65.6-97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients. With a median follow-up of 65.6 months (range 4.0-96.5), the median progression-free survival (PFS) was 47.6 months (range 4.0-93.3) and median overall survival (OS) was not reached. The 5-year PFS was 40% (90% CI: 19.9-59.5%) and 5-year OS was 71.8% (90% CI: 46.8-86.5%). Overall, (90)Y ibritumomab tiuxetan was well tolerated and led to long-term responses and PFS rates. PMID:25315074

  5. Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma.

    PubMed

    Gordon, Leo I; Witzig, Thomas; Molina, Arturo; Czuczman, Myron; Emmanouilides, Christos; Joyce, Robin; Vo, Katie; Theuer, Charles; Pohlman, Brad; Bartlett, Nancy; Wiseman, Greg; Darif, Mohamed; White, Christine

    2004-09-01

    We report updated time-to-event variables of a phase III randomized study comparing yttrium 90-labeled ibritumomab with rituximab standard therapy in 143 rituximab-naive patients with relapsed or refractory low-grade, follicular, or transformed CD20+ non-Hodgkin's lymphoma (NHL). Most patients (79%) had follicular lymphoma. Patients were randomized to receive a single intravenous (I.V.) dose of 90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m2 I.V. weekly for 4 doses (n = 70). The radioimmunotherapy group was pretreated with 2 rituximab doses (250 mg/m2) to improve biodistribution and one dose of Indium 111-labeled ibritumomab tiuxetan for imaging. The overall response rate was 80% versus 56% (P = 0.002) and complete response (CR)/CR unconfirmed (CRu) rates were 34% for 90Y ibritumomab tiuxetan versus 20% for rituximab. With a median follow-up of 44 months, the data are mature as all ongoing patients in both groups exceeded the median Kaplan-Meier estimated time to progression (TTP), duration of response (DR), and time to next therapy. Although this study was not powered to detect differences in time-to-event variables, the results from this randomized trial demonstrate trends toward longer median TTP (15 vs. 10.2 months; P = 0.07), DR (16.7 vs. 11.2 months; P = 0.44) and time to next therapy (21.1 vs. 13.8 months; P = 0.27) in follicular NHL patients treated with 90Y ibritumomab tiuxetan compared with the rituximab control arm. In patients achieving a CR/CRu, the median TTP was 24.7 months for patients treated with 90Y ibritumomab tiuxetan compared with 13.2 months for rituximab-treated patients (P = 0.41), and ongoing responses of > 5 years have been observed. These results confirm that 90Y ibritumomab tiuxetan produces high response rates and durable remissions in patients with previously treated low-grade, follicular, and transformed NHL. PMID:15453924

  6. RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution

    PubMed Central

    Andrade Campos, Marcio Miguel; Montes Limón, Anel E.; Grasa, Jose María; Lievano, Paola; Baringo, Teresa; Giraldo, Pilar

    2012-01-01

    Background. Based on historical data we reviewed our hospital clinical database to analyse our updated information and therapy outcomes of follicular non-Hodgkin lymphoma (F-NHL) patients treated with 90Y-Ibritumomab tiuxetan. Patients and Methods. Between 2005 and 2011, 56 F-NHL patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. All patients received 0.3 or 0.4 mCi/kg IV (88%) of 90Y-IT; response evaluation was performed 12 weeks after. Results. M/F 44.6%/55.4%, mean age 61.45 years (30–85); ECOG 0-1 96.9%. According to FLIPI score, distribution were good: 58.5%, intermediate: 29.2%, and poor: 12.3%. Previous therapies: >2: 40% (26). ORR was 94.6% (53/56). CR: 85.7%; CR according to previous disease: relapsed disease: 90% (27/30), refractory disease: 42.85% (3/7), consolidation with CR: 92.85% (13/14), and consolidation with PR: 100% (5/5). Global PR and NR were 8.9% (5) and 5.3% (3), respectively. Mean OS 63.86 months with a mean follow-up time of 57 months (2–73). Mean TTP: 52.65 months (95% CI: 43.83–61.48). Median OS and TTP were not achieved. No hospital submissions or deaths were registered. Conclusions. This study confirms the safety and high efficacy of 90Y-IT in F-NHL patients, RIT in early stage of disease could improve outcomes. PMID:23049552

  7. External Beam Radiotherapy Followed by {sup 90}Y Ibritumomab Tiuxetan in Relapsed or Refractory Bulky Follicular Lymphoma

    SciTech Connect

    Burdick, Michael J.; Neumann, Donald; Pohlman, Brad; Reddy, Chandana A.; Tendulkar, Rahul D.; Macklis, Roger

    2011-03-15

    Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan ({sup 90}Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by {sup 90}Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery of complete blood counts (CBC), {sup 90}Y-IT was administered at a dose of 0.3 or 0.4 mCi/kg depending on platelet counts. Hematologic toxicity was monitored through weekly CBC. Response was measured by positron emission tomography/CT or CT 3-4 months after {sup 90}Y-IT. Results: Only 2 patients required prolonged breaks between EBRT and {sup 90}Y-IT. The median time after {sup 90}Y-IT for platelets to recover to >100,000/ml was 55 days (range, 41-128 days). Platelet counts for 1 patient, who had received 4 previous chemotherapy regimens, never reached 100,000/ml. The complete and overall responses to combined therapy as measured 3-4 months after {sup 90}Y-IT were 64%. No patients relapsed within the EBRT field. With a median follow-up of 36.1 months, 6 patients have relapsed, 2 of whom have died. Median progression-free survival was 17.5 months. Conclusions: In contrast to prior failure analysis data for RRBFL patients treated with {sup 90}Y-IT alone, a brief course of EBRT prevented relapse in sites of BD. EBRT used to pretreat bulky sites may improve clinical outcomes and potentially extend survival when combined with {sup 90}Y-IT.

  8. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease.

    PubMed

    Samaniego, Felipe; Berkova, Zuzana; Romaguera, Jorge E; Fowler, Nathan; Fanale, Michelle A; Pro, Barbara; Shah, Jatin J; McLaughlin, Peter; Sehgal, Lalit; Selvaraj, Vijairam; Braun, Frank K; Mathur, Rohit; Feng, Lei; Neelapu, Sattva S; Kwak, Larry W

    2014-10-01

    (90) Y-ibritumomab-tiuxetan ((90) YIT) was used as a first-line therapy for patients with early-stage follicular lymphoma (FL) or marginal zone B-cell lymphoma (MZL). Thirty-one patients were treated, with an overall 3-month response rate of 100% (68% complete response, 29% unconfirmed complete response and 3% partial response). At a median follow-up of 56 months, ten patients (32%) had disease relapse or progression. The progression-free rates at 3 and 5 years were lower in males, patients with FL, stage II disease and non-bulky disease, although they did not reach statistical significance. Grade 3-4 neutropenia, thrombocytopenia and anaemia were 61%, 35%, and 3%, respectively. (90) YIT was well tolerated, including in those patients over 60 years old, and achieved high response rates in patients with early-stage low-grade B-cell lymphomas. Bulky disease did not adversely affect tumour response. PMID:25040450

  9. Pilot trial of yttrium-90 ibritumomab tiuxetan consolidation following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in patients with limited-stage, bulky diffuse large B-cell lymphoma.

    PubMed

    Yang, Deok-Hwan; Kim, Won Seog; Kim, Seok Jin; Kim, Jin Seok; Kwak, Jae-Yong; Chung, Joo Seop; Oh, Sung Yong; Suh, Cheolwon; Lee, Je-Jung

    2012-05-01

    The clinical efficacy and safety of yttrium-90 ((90)Y)-ibritumomab tiuxetan consolidation treatment following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy was investigated in patients with limited-stage and bulky diffuse large B-cell lymphoma (DLBCL). This prospective, multi-center, pilot trial included 21 patients who were newly diagnosed with stage I/II, bulky DLBCL and achieved a complete or partial response after six cycles of R-CHOP. The median size of bulky disease was 10.0 × 7.0 cm. After a median follow-up of 28.8 months, the overall response rate after (90)Y-ibritumomab tiuxetan consolidation treatment was 80.9%, including 4.8% partial response. However, six patients (28.6%) experienced a progression or relapse. The 3-year overall and progression-free survival rates were 85.0 ± 8.0% and 75.0 ± 9.7%, respectively. Grade 3-4 adverse events were mainly hematologic toxicities, such as thrombocytopenia (35%) and neutropenia (60%). One patient experienced grade 3 Pneumocystis carinii pneumonitis. Thus, (90)Y-ibritumomab tiuxetan consolidation following six cycles of R-CHOP resulted in an acceptable response with tolerable toxicity in patients with limited-stage and bulky DLBCL. PMID:22035417

  10. Phase I study of radioimmunotherapy with an anti-CD20 murine radioimmunoconjugate ((90)Y-ibritumomab tiuxetan) in relapsed or refractory indolent B-cell lymphoma.

    PubMed

    Watanabe, Takashi; Terui, Shoji; Itoh, Kuniaki; Terauchi, Takashi; Igarashi, Tadahiko; Usubuchi, Noriko; Nakata, Masanobu; Nawano, Shigeru; Sekiguchi, Naohiro; Kusumoto, Shigeru; Tanimoto, Kazuki; Kobayashi, Yukio; Endo, Keigo; Seriu, Taku; Hayashi, Masaki; Tobinai, Kensei

    2005-12-01

    We conducted a phase I study to evaluate the safety and efficacy of radioimmunotherapy with yttrium-90-ibritumomab tiuxetan (Y2B8) in Japanese patients with relapsed or refractory indolent B-cell lymphoma. Indium-111-labeled ibritumomab tiuxetan (In2B8; 3.5 or 5 mCi [129.5 or 185 MBq]) was administered on day 1, followed by serial gamma-camera imaging to investigate the distribution of In2B8 in the whole body of patients and to judge the feasibility of Y2B8 administration. Y2B8 with a dose of 0.3 mCi/kg (11.1 MBq/kg) or 0.4 mCi/kg (14.8 MBq/kg) was administered on day 8. Grade 4 neutropenia and grade 3 thrombocytopenia were observed in three of nine of the patients evaluated for safety. Critical toxicities (prolonged thrombocytopenia or severe non-hematological toxicities) were observed in two of six patients in the 0.4 mCi/kg (14.8 MBq/kg) dose group but were not seen in any of the three patients in the 0.3 mCi/kg (11.1 MBq/kg) dose group. The non-hematological toxicities of the nine patients were of grade 2 or less, except in two patients who had been heavily treated previously. They experienced critical toxicities such as infection, diarrhea, hyponatremia and prolonged thrombocytopenia, as well as other frequent grade 2 non-hematological toxicities. Although the pharmacokinetic profiles were similar to those in the US study, one of the two patients was clarified retrospectively as showing abnormal biodistribution of In2B8 in the bone marrow, as judged by an independent third party panel of radiologists. Five of the 10 participants achieved complete responses or unconfirmed complete responses and two partial responses. In conclusion, the recommended dose of Y2B8 for the subsequent phase II study for Japanese patients is 0.4 mCi/kg (14.8 MBq/kg). This dose of radioimmunotherapy was feasible when patients with altered biodistribution of In2B8 were excluded, and it was highly effective. (Cancer Sci 2005; 96: 903-910). PMID:16367911

  11. Late Occurrence of PML in a Patient Treated for Lymphoma with Immunomodulatory Chemotherapies, Bendamustine, Rituximab, and Ibritumomab Tiuxetan

    PubMed Central

    Lane, Michael A.; Renga, Vijay; Pachner, Andrew R.; Cohen, Jeffrey A.

    2015-01-01

    PML caused by John Cunningham (JC) virus is a rare but an increasingly recognized entity. With the advent of newer immunomodulatory therapies with monoclonal antibodies, there is an increasing incidence of PML. Initially concern was restricted to patients treated for multiple sclerosis with natalizumab but more case reports are being reported during treatment for other conditions like Crohn's disease and lymphoma with agents such as rituximab. We report the case of a 66-year-old woman who developed PML a year after completion of therapy with rituximab, ibritumomab, and bendamustine. PMID:25705531

  12. Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.

    PubMed

    Andrade-Campos, Marcio Miguel; Montes-Limón, Anel E; Soro-Alcubierre, Gloria; Grasa, José María; Lopez-Gómez, Luis; Baringo, Teresa; Giraldo, Pilar

    2014-12-01

    The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ≥5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL. PMID:24985089

  13. Phase I trial of (90)Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation.

    PubMed

    Vose, Julie M; Bierman, Philip J; Loberiza, Fausto R; Bociek, Robert G; Matso, Daniel; Armitage, James O

    2007-04-01

    Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT. PMID:17454625

  14. Autologous stem cell transplantation after conditioning with yttrium-90 ibritumomab tiuxetan plus BEAM in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial

    PubMed Central

    Briones, Javier; Novelli, Silvana; García-Marco, José A.; Tomás, José F.; Bernal, Teresa; Grande, Carlos; Canales, Miguel A.; Torres, Antonio; Moraleda, José M.; Panizo, Carlos; Jarque, Isidro; Palmero, Francisca; Hernández, Miguel; González-Barca, Eva; López, Dulce; Caballero, Dolores

    2014-01-01

    Lymphoma patients with persistent disease undergoing autologous transplantation have a very poor prognosis in the rituximab era. The addition of radioimmunotherapy to the conditioning regimen may improve the outcome for these patients. In a prospective, phase 2 study, we evaluated the safety and efficacy of the addition of 90Y-ibritumomab tiuxetan to the conditioning chemotherapy in patients with refractory diffuse large B-cell lymphoma. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. The median age of the patients was 53 years (range, 25–67). All patients were given 90Y-ibritumomab tiuxetan at a fixed dose of 0.4 mCi/kg (maximum dose 32 mCi) 14 days prior to the preparative chemotherapy regimen. Histological examination showed that 22 patients had de novo diffuse large B-cell lymphoma and eight had transformed diffuse large B-cell lymphoma. All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. The median time to neutrophil recovery (>500 white blood cells/μL) was 11 days (range, 9–21), while the median time to platelet recovery (>20,000 platelets/μL) was 13 days (range, 11–35). The overall response rate at day +100 was 70% (95% CI, 53.6–86.4) with 60% (95% CI, 42.5–77.5) of patients obtaining a complete response. After a median follow-up of 31 months for alive patients (range, 16–54), the estimated 3-year overall and progression-free survival rates are 63% (95% CI, 48–82) and 61% (95% CI, 45–80), respectively. We conclude that autologous transplantation with conditioning including 90Y-ibritumomab tiuxetan is safe and results in a very high response rate with promising survival in this group of patients with refractory diffuse large B-cell lymphoma with a very poor prognosis. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2007

  15. Bortezomib may be safely combined with Y-90-ibritumomab tiuxetan in patients with relapsed/refractory follicular non-Hodgkin lymphoma: a phase I trial of combined induction therapy and bortezomib consolidation.

    PubMed

    Roy, Rupali; Evens, Andrew M; Patton, David; Gallot, Lillia; Larson, Annette; Rademaker, Alfred; Cilley, Jeffrey; Spies, Stewart; Variakojis, Daina; Gordon, Leo I; Winter, Jane N

    2013-03-01

    Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen. PMID:22906230

  16. The use of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in high-risk patients with diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation

    PubMed Central

    Kisiel, Elżbieta; Sawczuk-Chabin, Joanna; Centkowski, Piotr; Knopińska-Posłuszny, Wanda; Khan, Omeir

    2015-01-01

    Aim of the study To evaluate the efficacy and safety of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in the management of DLBCL. Material and methods Patients with primary refractory or high-risk DLBCL (n = 18), ineligible for autologous stem-cell transplantation, were included in a retrospective study performed at three centers by the Polish Lymphoma Research Group (PLRG). All patients (mean age 61, range 35–82) either didn't achieve a complete response or didn't complete the scheduled therapy due to its complications. Response rates (CR, PR, SD, PD) according to Cheson criteria, overall survival (OS), progression-free survival (PFS) and adverse effects of radioimmunotherapy were analyzed. Results Consolidation radioimmunotherapy increased the CR rate from 38% (n = 7) to 82% (n = 15). One patient remained in PR, one patient remained in SD, while one patient remained in PD. During a median follow-up of five years, 11 patients (62%) were alive with no recurrence, 4 patients (22%) were alive with relapse while 3 patients (16%) died. There was no statistically significant difference in PFS between those in CR and those in PR before 90Y-IT. Conclusions Radioimmunotherapy is an effective consolidation therapy for high risk/refractory DLBCL patients and worthy of further investigation in prospective trials. PMID:26199570

  17. Short-course R-CHOP followed by 90Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results

    PubMed Central

    Stefoni, V; Casadei, B; Bottelli, C; Gaidano, G; Ciochetto, C; Cabras, M G; Ansuinelli, M; Argnani, L; Broccoli, A; Gandolfi, L; Pellegrini, C; Zinzani, P L

    2016-01-01

    An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with 90Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration. PMID:27176801

  18. 90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7 years.

    PubMed

    Casadei, Beatrice; Pellegrini, Cinzia; Pulsoni, Alessandro; Annechini, Giorgia; De Renzo, Amalia; Stefoni, Vittorio; Broccoli, Alessandro; Gandolfi, Letizia; Quirini, Federica; Tonialini, Lorenzo; Morigi, Alice; Argnani, Lisa; Zinzani, Pier Luigi

    2016-06-01

    Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan ((90) Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by (90) Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma. PMID:26990782

  19. Short-course R-CHOP followed by (90)Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results.

    PubMed

    Stefoni, V; Casadei, B; Bottelli, C; Gaidano, G; Ciochetto, C; Cabras, M G; Ansuinelli, M; Argnani, L; Broccoli, A; Gandolfi, L; Pellegrini, C; Zinzani, P L

    2016-01-01

    An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with (90)Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration. PMID:27176801

  20. First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group

    PubMed Central

    Arranz, Reyes; García-Noblejas, Ana; Grande, Carlos; Cannata-Ortiz, Jimena; Sánchez, José J.; García-Marco, José-Antonio; Aláez, Concepción; Pérez-Calvo, Javier; Martínez-Sánchez, Pilar; Sánchez-González, Blanca; Canales, Miguel-Angel; Conde, Eulogio; Martín, Alejandro; Arranz, Eva; Terol, María-José; Salar, Antonio; Caballero, Dolores

    2013-01-01

    The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with 90Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of 90Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60–93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4–59.6), 52% (95% confidence interval 32.4–71.6) and 81% (95% confidence interval 67.28–94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48–78.52) and 87% (95% confidence interval 70–100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3–4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. Trial registration: clinical.gov identifier

  1. Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group.

    PubMed

    Provencio, Mariano; Cruz Mora, Miguel Á; Gómez-Codina, José; Quero Blanco, Cristina; Llanos, Marta; García-Arroyo, Francisco R; de la Cruz, Luis; Gumá Padró, Josep; Delgado Pérez, Juan R; Sánchez, Antonio; Alvarez Cabellos, Ruth; Rueda, Antonio

    2014-01-01

    Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL. PMID:23573825

  2. Ibritumomab Injection

    MedlinePlus

    ... is in a class of medications called monoclonal antibodies with radioisotopes. It works by attaching to cancer ... you receive ibritumomab injection, your body may develop antibodies (substances in the blood that help the immune ...

  3. Ibritumomab Injection

    MedlinePlus

    ... have received ibritumomab injection.do not have any vaccinations without talking to your doctor.you should know ... cells) and myelodysplastic syndrome (condition in which blood cells do not ... online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

  4. Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

    ClinicalTrials.gov

    2016-06-15

    Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

  5. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    ClinicalTrials.gov

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  6. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-01-04

    Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  7. Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-02-17

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  8. Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-03-21

    B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  9. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  10. Immunoscintigraphy with 111In antimyosin Fab.

    PubMed

    Morguet, A J; Munz, D L; Kreuzer, H; Emrich, D

    1990-11-01

    Monoclonal 111In antimyosin Fab is a marker for myocytes which have lost their membrane integrity. Because of the slow blood pool clearance of the radiopharmaceutical, imaging is usually started 24-48 h after intravenous injection of 74 MBq of the tracer. This long postinjection interval restricts its utilization in the primary diagnosis of acute myocardial infarction. However, antimyosin may help to differentiate between necrotic and viable myocardium in the subacute stage of incomplete myocardial infarction. Serial endomyocardial biopsy for early detection of transplant rejection after heart transplantation may be partially replaced or supplemented by antimyosin scintigraphy. The compound may facilitate the diagnosis of myocarditis. Other potential indications may be prognostic assessment of dilated cardiomyopathy, monitoring cardiotoxic side-effects of chemotherapeutics, recognition of cardiac contusion as well as diagnosis of rhabdo- and leiomyosarcoma. In specific clinical situations 111In antimyosin Fab immunoscintigraphy may provide valuable diagnostic information. PMID:2277688

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

    (+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19649342

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  13. Killing of human lung cancer cells using a new ( sup 111 In)bleomycin complex ( sup 111 In)BLMC

    SciTech Connect

    Hou, D.Y.; Hamburger, A.W.; Beach, J.L.; Maruyama, Y. )

    1989-01-01

    The ability of a ({sup 111}In)bleomycin complex (({sup 111}In)BLMC) to kill five cell lines of human lung cancer (small cell lung cancer) was investigated. Cells were exposed to either 0.9% NaCl, ({sup 111}In)Cl3, BLM, ({sup 111}In)BLMC, nonradioactive InCl3, or In-BLMC for 60 minutes, plated in soft agarose, and assessed for colony formation. ({sup 111}In)BLMC (40-200 microCi carried by 15-25 micrograms BLM/ml) was more cytotoxic than BLM (15-25 micrograms BLM/ml) by a factor of 1.6-5.3 for five cell lines. The percent survival of N417 cells was 28.4 for ({sup 111}In)BLMC (40 microCi/15 micrograms BLM/ml) and 54.3 for BLM (15 micrograms/ml); 1.9 for ({sup 111}In)BLMC (200 microCi/25 micrograms BLM/ml), and 10.0 for BLM (25 micrograms/ml). {sup 111}InCl3 (200 microCi/ml) and nonradioactive InCl3 failed to inhibit colony formation. The new ({sup 111}In)BLMC may be useful for therapy of some lung cancer patients.

  14. Osteomyelitis complicating fracture: pitfalls of /sup 111/In leukocyte scintigraphy

    SciTech Connect

    Kim, E.E.; Pjura, G.A.; Lowry, P.A.; Gobuty, A.H.; Traina, J.F.

    1987-05-01

    /sup 111/In-labeled leukocyte imaging has shown greater accuracy and specificity than alternative noninvasive methods in the detection of uncomplicated osteomyelitis. Forty patients with suspected osteomyelitis complicating fractures (with and without surgical intervention) were evaluated with /sup 111/In-labeled leukocytes. All five patients with intense focal uptake, but only one of 13 with no uptake, had active osteomyelitis. However, mild to moderate /sup 111/In leukocyte uptake, observed in 22 cases, indicated the presence of osteomyelitis in only four of these; the other false-positive results were observed in noninfected callus formation, heterotopic bone formation, myositis ossificans, and sickle-cell disease. These results suggest that /sup 111/In-labeled leukocyte imaging is useful for the evaluation of suspected osteomyelitis complicating fracture but must be used in conjunction with clinical and radiographic correlation to avoid false-positive results.

  15. Development of 111In-labeled porphyrins for SPECT imaging

    PubMed Central

    Sadeghi, Shaghayegh; Mirzaei, Mohammad; Rahimi, Mohammad; Jalilian, Amir R.

    2014-01-01

    Objective(s): The aim of this research was the development of 111In-labeled porphyrins as possible radiopharmaceuticals for the imaging of tumors. Methods: Ligands, 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) porphyrin) (TDHPP), 5, 10, 15, 20-tetrakis (4-hydroxyphenyl) porphyrin (THPP) and 5, 10, 15, 20-tetrakis (3,4-dimethoxyphenyl) porphyrin) (TDMPP) were labeled with 111InCl3 (produced from proton bombardment of natCd target) in 60 min at 80 ºC. Quality control of labeled compounds was performed via RTLC and HPLC followed by stability studies in final formulation and presence of human serum at 37 ºC for 48 h as well as partition coefficient determination. The biodistribution studies performed using tissue dissection and SPECT imaging up to 24h. Results: The complexes were prepared with more than 99% radiochemical purity (HPLC and RTLC) and high stability to 48 h. Partition coefficients (calculated as log P) for 111In-TDHPP, 111In-THPP and 111In-TDMPP were 0.88, 0.8 and 1.63 respectively. Conclusion: Due to urinary excretion with fast clearance for 111In-TDMPP, this complex is probably a suitable candidate for considering as a possible tumor imaging agent. PMID:27408865

  16. /sup 111/In-/sup 109/In mass difference

    SciTech Connect

    Takagui, E.M.; Dietzsch, O.

    1980-04-01

    A measurement of the difference of Q values for the /sup 108/Cd(/sup 3/He,d)/sup 109/In and the /sup 110/Cd(/sup 3/He,d)/sup 111/In reactions shows a significant discrepancy with the value from the 1977 Atomic Mass Tables. We find Q(/sup 110/Cd(/sup 3/He,d)/sup 111/In) -Q(/sup 108/Cd(/sup 3/He,d)/sup 109/In)=806.5 +- 2.6 keV, leading to a new improved mass excess difference for /sup 111/In-/sup 109/In of -1904.5 +- 7.5 keV.

  17. Monitoring of cardiac antirejection therapy with /sup 111/In lymphocytes

    SciTech Connect

    Lerch, R.A.; Bergmann, S.R.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-06-01

    To determine whether lymphocytes labeled with /sup 111/In permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with /sup 111/In were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of /sup 111/In lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with /sup 111/In-labeled lymphocytes will permit noninvasive assessment of antirejection therapy.

  18. Standardisation and half-life measurements of (111)In.

    PubMed

    Dziel, Tomasz; Listkowska, Anna; Tymiński, Zbigniew

    2016-03-01

    The standardisation of (111)In by 4π(LS)-γ coincidence and anticoincidence counting is presented. Absolute measurements were performed for samples with different concentrations of carrier solution and for different window settings in the gamma channel. The radioactive concentration of the master solution determined on the same reference date was consistent for all measurements performed. The evaluated typical uncertainty was 0.43%. The half-life of (111)In was determined using a time series of measurements performed with an ionisation chamber. A least squares fit of the measured data resulted in a half-life of 2.8067 (34) days consistent with Decay Data Evaluation Project recommended value (0.064% higher than the DDEP value). PMID:26651174

  19. [Pharmacokinetic substantiation of the use of 111In-citrate in bone marrow studies].

    PubMed

    Korsunskiĭ, V N; Tarasenko, Iu I; Koval'chuk, N D; Kosheleva, I Iu; Popov, V I

    1986-07-01

    Soviet radiopharmaceutical 111In-citrin has been studied to define its possible application for marrow visualization. 111In-citrin has been shown to accumulate in the red marrow, parenchymal organs and to be excreted from animal organism by urinary system predominately. 111In-citrin has advantages in defining the nuclide concentrations in marrow blood and serum as compared with colloid preparations and 111In-chloride. 111In-citrin is supposed to be an adequate radiopharmaceutical preparation for visualization of the red marrow. PMID:3736386

  20. 16. VIEW LOOKING NORTHEAST AT BUILDING 11 (111) IN 1952. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. VIEW LOOKING NORTHEAST AT BUILDING 11 (111) IN 1952. IN 1952, BUILDINGS 11 (111), 12 (121), 21 (221), 22 (122), 23 (123), AND 42 (442) WERE OCCUPIED. BUILDINGS 91 (991) AND 81 (881) WERE OPERATIONAL. BUILDINGS 44 (444) AND 71 (771) WERE UNDER CONSTRUCTION. THE TOTAL COST FOR CONSTRUCTION BY 1952 WAS $2.5 MILLION. BY SEPTEMBER OF 1953, AUSTIN COMPANY HAD COMPLETED 21 BUILDINGS FOR AN APPROXIMATE COST OF $43.3 MILLION (1952). - Rocky Flats Plant, Bounded by Indiana Street & Routes 93, 128 & 72, Golden, Jefferson County, CO

  1. In situ 111In-doping for achieving biocompatible and non-leachable 111In-labeled Fe3O4 nanoparticles.

    PubMed

    Zeng, Jianfeng; Jia, Bing; Qiao, Ruirui; Wang, Chao; Jing, Lihong; Wang, Fan; Gao, Mingyuan

    2014-02-28

    The present study reports a new approach for synthesizing (111)In-radiolabeled biocompatible Fe3O4 nanoparticles. Radioactive (111)In is doped in situ into the lattice of Fe3O4 nanoparticles to achieve robust radiolabeling for accurately tracing PEGylated Fe3O4 particles in vivo. PMID:24430864

  2. Diagnosis of osteomyelitis of the foot in diabetic patients: Value of 111In-leukocyte scintigraphy

    SciTech Connect

    Larcos, G.; Brown, M.L.; Sutton, R.T. )

    1991-09-01

    The noninvasive diagnosis of osteomyelitis of the foot in diabetic patients with currently available radiologic and radionuclide imaging techniques is often difficult. Recently, 111In-labeled leukocyte scintigraphy has been proposed as an attractive alternative. Accordingly, the authors retrospectively reviewed 51 111In-labeled leukocyte scans, 49 technetium-99m bone scans, and 49 plain radiographs obtained in 51 adults with diabetes in whom osteomyelitis of the foot was suspected. The sensitivity and specificity of these techniques were evaluated in all patients, as well as in a subgroup of 11 patients with neuroarthropathy. Results with 111In-labeled leukocyte scans were also examined in subsets of patients with soft-tissue ulcers (n = 35) and those receiving antibiotics during investigation (n = 20). Confirmation or exclusion of osteomyelitis was made surgically in 28 patients and clinically in 23. Fourteen patients had osteomyelitis. Bone scans were most sensitive (93%) but least specific (43%); plain radiographs were most specific (83%) but least sensitive (43%). 111In-labeled leukocyte scans were both sensitive (79%) and specific (78%), and remained useful in patients with neuroarthropathy, soft-tissue ulcers, and antibiotic treatment. Poor spatial resolution contributed to the false-negative and false-positive 111In-labeled leukocyte scans, suggesting that this technique should not be interpreted independent of other tests. 111In-labeled leukocyte scans are a valuable diagnostic tool for the diagnosis of pedal osteomyelitis in diabetic patients.

  3. sup 111 In-labeled nonspecific immunoglobulin scanning in the detection of focal infection

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Callahan, R.J.; Khaw, B.A.; Keech, F.; Ahmad, M.; Wilkinson, R.; Strauss, H.W. )

    1989-10-05

    We performed radionuclide scanning after the intravenous injection of human IgG labeled with indium-111 in 128 patients with suspected focal sites of inflammation. Localization of 111In-labeled IgG correlated with clinical findings in 51 infected patients (21 with abdominal or pelvic infections, 11 with intravascular infections, 7 with pulmonary infections, and 12 with skeletal infections). Infecting organisms included gram-positive bacteria, gram-negative bacteria, Pneumocystis carinii, Mycoplasma pneumoniae, and Candida albicans. No focal localization of 111In-labeled IgG was observed in 63 patients without infection. There were five false negative results, and nine results were unusable. Serial scans were carried out in eight patients: continued localization correctly predicted relapse in six, and the absence of localization indicated resolution in two. To determine whether 111In-labeled IgG localization was specific for inflammation, we studied 16 patients with cancer. Focal localization occurred in 13 of these patients (5 with melanomas, 5 with gynecologic cancers, and 1 each with lymphoma, prostate cancer, and malignant fibrous histiocytoma). No localization was seen in patients with renal or colon cancer or metastatic medullary carcinoma of the thyroid. We conclude that 111In-labeled IgG imaging is effective for the detection of focal infection and that serial scans may be useful in assessing therapeutic efficacy. This technique may also be helpful in the evaluation of certain cancers.

  4. Relative Biologic Effects of Low-Dose-Rate {alpha}-Emitting {sup 227}Th-Rituximab and {beta}-Emitting {sup 90}Y-Tiuexetan-Ibritumomab Versus External Beam X-Radiation

    SciTech Connect

    Dahle, Jostein Bruland, Oyvind S.; Larsen, Roy H.

    2008-09-01

    Purpose: To determine the relative biologic effects (RBE) of {alpha}-particle radiation from {sup 227}Th-rituximab and of {beta}-radiation from {sup 90}Y-tiuexetan-ibritumomab (Zevalin) compared with external beam X-radiation in the Raji lymphoma xenograft model. Methods and Materials: Radioimmunoconjugates were administered intravenously in nude mice with Raji lymphoma xenografts at different levels of activity. Absorbed dose to tumor was estimated by separate biodistribution experiments for {sup 227}Th-rituximab and Zevalin. Tumor growth was measured two to three times per week after injection or X-radiation. Treatment-induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm{sup 3}, respectively, was used as an end point. Results: The absorbed radiation dose-rate in tumor was slightly more than 0.1 Gy/d for the first week following injection of {sup 227}Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days after injection. For treatment with Zevalin the maximum dose-rate in tumor was achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01 Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for {sup 227}Th-rituximab and between 1 and 1.3 for Zevalin. Conclusions: Both at low doses and low-dose-rates, the {sup 227}Th-rituximab treatment was more effective per absorbed radiation dose unit than the two other treatments. The considerable effect at low doses suggests that the best way to administer low-dose-rates, {alpha}-emitting radioimmunoconjugates is via multiple injections.

  5. Diagnosis of arterial prosthetic graft infection by /sup 111/In oxine white blood cell scans

    SciTech Connect

    McKeown, P.P.; Miller, D.C.; Jamieson, S.W.; Mitchell, R.S.; Reitz, B.A.; Olcott, C.; Mehigan, J.T.; Silberstein, R.J.; McDougall, I.R.

    1982-08-01

    Early and accurate diagnosis of infected prosthetic arterial grafts is difficult, despite the application of diverse diagnostic modalities. Delay in making the diagnosis is largely responsible for the high amputation and mortality rates associated with this complication. In nine patients with suspected graft infections, /sup 111/In white blood cell scanning was useful and accurate. Graft infection was proved in five cases and ruled out in three. One false-positive scan was due to a sigmoid diverticular abscess overlying the graft. /sup 111/In white blood cell scans may improve the accuracy of diagnosing infected prosthetic grafts, which may result in better limb and patient salvage rates.

  6. Esthesioneuroblastoma (olfactory neuroblastoma) treated with 111In-octreotide and 177Lu-DOTATATE PRRT.

    PubMed

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-04-01

    A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma. PMID:25674857

  7. Quantitative simultaneous 111In/99mTc SPECT-CT of osteomyelitis

    PubMed Central

    Cervo, Morgan; Gerbaudo, Victor H.; Park, Mi-Ae; Moore, Stephen C.

    2013-01-01

    Purpose: A well-established approach for diagnostic imaging of osteomyelitis (OM), a bone infection, is simultaneous SPECT-CT of 99mTc sulfur colloid (SC) and 111In white blood cells (WBC). This method provides essentially perfect spatial registration of the tracers within anatomic sites of interest. Currently, diagnosis is based purely on a visual assessment—where relative discordance between 99mTc and 111In uptake in bone, i.e., high 111In and low 99mTc, suggests OM. To achieve more quantitative images, noise, scatter, and crosstalk between radionuclides must be addressed through reconstruction. Here the authors compare their Monte Carlo-based joint OSEM (MC-JOSEM) algorithm, which reconstructs both radionuclides simultaneously, to a more conventional triple-energy window-based reconstruction (TEW-OSEM), and to iterative reconstruction with no compensation for scatter (NC-OSEM). Methods: The authors created numerical phantoms of the foot and torso. Multiple bone-infection sites were modeled using high-count Monte Carlo simulation. Counts per voxel were then scaled to values appropriate for 111In WBC and 99mTc SC imaging. Ten independent noisy projection image sets were generated by drawing random Poisson deviates from these very low-noise images. Data were reconstructed using the two iterative scatter-compensation methods, TEW-OSEM and MC-JOSEM, as well as the uncorrected method (NC-OSEM). Mean counts in volumes of interest (VOIs) were used to evaluate the bias and precision of each method. Data were also acquired using a phantom, approximately the size of an adult ankle, consisting of regions representing infected and normal bone marrow, within a bone-like attenuator and surrounding soft tissue; each compartment contained a mixture of 111In and 99mTc. Low-noise data were acquired during multiple short scans over 29 h on a Siemens Symbia T6 SPECT-CT with medium-energy collimators. Pure 99mTc and 111In projection datasets were derived by fitting the acquired

  8. Evaluation of [111In]-Labeled Zinc-Dipicolylamine Tracers for SPECT Imaging of Bacterial Infection

    PubMed Central

    Rice, Douglas R.; Plaunt, Adam J.; Turkyilmaz, Serhan; Smith, Miles; Wang, Yuzhen; Rusckowski, Mary

    2015-01-01

    Purpose This study prepared three structurally related zinc-dipicolylamine (ZnDPA) tracers with [111In] labels and conducted biodistribution and SPECT/CT imaging studies of a mouse leg infection model. Methods Two monovalent tracers, ZnDPA-[111In]DTPA and ZnDPA-[111In]DOTA, each with a single zinc-dipicolylamine targeting unit, and a divalent tracer, Bis(ZnDPA)-[111In]DTPA,with two zinc-dipicolylamine units were prepared. Organ biodistribution and SPECT/CT imaging studies were performed on living mice with a leg infection created by injection of clinically relevant Gram positive Streptococcus pyogenes. Fluorescent and luminescent Eu3+-labeled versions of these tracers were also prepared and used to measure relative affinity for the exterior membrane surface of bacterial cells and mimics of healthy mammalian cells. Results All three 111In-labeled radiotracers were prepared with radiopurity > 90%. The biodistribution studies showed that the two monovalent tracers were cleared from the body through the liver and kidney, with retained % injected dose for all organs of < 8 % at 20 hours and infected leg T/NT ratio of ≤ 3.0. Clearance of the divalent tracer from the bloodstream was slower and primarily through the liver, with a retained % injected dose for all organs < 37% at 20 hours and T/NT ratio rising to 6.2 after 20 hours. The SPECT/CT imaging indicated the same large difference in tracer pharmacokinetics and higher accumulation of the divalent tracer at the site of infection. Conclusions All three [111In]-ZnDPA tracers selectively targeted the site of a clinically relevant mouse infection model that could not be discerned by visual external inspection of the living animal. The highest target selectivity, observed with a divalent tracer equipped with two zinc-dipicolylamine targeting units, compares quite favorably with the imaging selectivities previously reported for other nuclear tracers that target bacterial cell surfaces. The tracer pharmacokinetics depended

  9. Radioimmunotherapy for non-Hodgkin's lymphoma: A review for radiation oncologists

    SciTech Connect

    Macklis, Roger M. . E-mail: macklir@ccf.org; Pohlman, Brad

    2006-11-01

    Purpose: The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of Radiation oncologist in administering this important new form of biologically targeted radiotherapy. Methods and Materials: A review of articles and abstracts on the clinical efficacy, safety, and radiation safety of yttrium Y 90 ({sup 9}Y) ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. Results: The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab. Both agents have produced significant responses in patients with low-grade, follicular, or transformed NHL, including patients with disease that had not responded or had responded poorly to previous chemotherapy or immunotherapy. Reversible toxicities such as neutropenia, thrombocytopenia, and anemia are the most common adverse events with both agents. Conclusions: Radioimmunotherapy is safe and effective in many patients with B-cell NHL. {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab can produce clinically meaningful and durable responses even in patients in whom chemotherapy has failed. Treatment with RIT requires a multispecialty approach and close communication between Radiation oncologist and other members of the treatment team. Radiation oncologist plays an important role in treating patients with RIT and monitoring them for responses and adverse events after treatment.

  10. Pediatric leptomeningeal metastasis: 111In-DTPA cerebrospinal fluid flow studies.

    PubMed

    Chamberlain, M C

    1994-04-01

    Nine children (five girls and four boys) ranging in age from 1 to 18 years (median age, 12 years) with leptomeningeal metastasis were evaluated for cerebrospinal fluid compartmentalization with cerebrospinal fluid flow studies using ventricular diethylenetriaminepentaacetic acid labeled with indium 111 (111In-DTPA). Histologic diagnosis included medulloblastoma (two), primitive neuroectodermal tumor (two), acute lymphoblastic leukemia (two), pineoblastoma (one), ependymoma (one), and anaplastic astrocytoma (one). Sixteen 111In-DTPA cerebrospinal fluid flow studies were performed, of which nine demonstrated normal anterograde cerebrospinal fluid flow of radionuclide, with the following cerebrospinal fluid compartment median times to appearance, with ranges in parentheses: ventricles, 1 minute (0 to 3 minutes); cisterna magna/basal cisterns, 5 minutes (3 to 5 minutes); cervical subarachnoid space, 8 minutes (5 to 10 minutes); thoracic subarachnoid space, 15 minutes (10 to 30 minutes); lumbar subarachnoid space, 35 minutes (20 to 45 minutes); and sylvian cistern, 80 minutes (60 to 90 minutes). Blockage of normal anterograde cerebrospinal fluid flow was seen in seven 111In-DTPA cerebrospinal fluid flow studies in the following cerebrospinal fluid compartments: cervical subarachnoid space (four), lumbar subarachnoid space (two), and cisterna magna/basal cisterns (one). Five 111In-DTPA cerebrospinal fluid flow studies were performed after demonstration of cerebrospinal fluid compartmentalization and treatment with limited-field radiation therapy to involved regions; cerebrospinal fluid flow blocks resolved in three. In conclusion, cerebrospinal fluid compartmentalization, as shown by radionuclide ventriculography, is a common occurrence in pediatric leptomeningeal metastasis (four of nine patients, or 44%) and may be palliated by involved-field radiotherapy. PMID:8006365

  11. Radioimmunodetection in rhabdo- and leiomyosarcoma with sup 111 In-anti-myosin monoclonal antibody complex

    SciTech Connect

    Planting, A.; Verweij, J.; Cox, P.; Pillay, M.; Stoter, G. )

    1990-02-01

    In patients with rhabdo- and leiomyosarcoma a radioimmunodiagnostic study was performed with {sup 111}In labeled F(ab) fragments of a monoclonal antibody against myosin. Eight patients with rhabdomyosarcoma and 18 patients with leiomyosarcoma were studied. Scanning was performed at 4, 24, and 48 h after administration of 74 MBeq of the antibody complex. A high uptake with a tumor:background ratio of 10:1 was observed in several patients with rhabdomyosarcoma but the results were less accurate in leiomyosarcoma.

  12. Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer.

    PubMed

    Vaccarili, M; Lococo, A; Fabiani, F; Staffilano, A

    2000-01-01

    Some years ago it was proved that a good percentage of small cell lung cancers, classified among cancers of the APUD system, produces somatostatin receptors that can be detected in vivo by scintigraphy with 111In-DTPA-octreotide. With the method in the whole body it is possible to identify the principal neoformation and the probable metastases. The authors present a study of 21 patients afflicted with small cell lung cancer diagnosed histologically. The study, carried out between January 1995 and December 1997, compared the radiologic iconography of the CT scan with the scintigraphic map obtained by a planar scintigraphy and in SPECT 1, 4 and 24-hr after iv injection of 110 MBq of 111In-DTPA-octreotide. The comparison was made with reference to the principal neoplasm and probable metastases. A scintigraphic study, a CT of restaging and a follow-up, done after 3 and 6 months of chemotherapy, on 15 patients with cancer that produces somatostatin receptors proved that the neoplasm sometimes regresses and sometimes progresses. In the latter case, it is possible to identify cerebral, mediastinal and hepatic metastases with the administration of 200 microg of octreotide 3 times a day for 7 days before the scintigraphy. In fact, the administration lowers background activity. The authors concluded that scintigraphy with 111In-DTPA-octreotide plays an important part in the study of patients afflicted with small cell lung cancer. Scintigraphy identifies the subgroups of patients who can be cured with somatostatin analogues together with chemotherapy. Scintigraphy presents a good sensibility in the re-staging and in the follow-up of patients who are treated, even though it is difficult to identify subdiaphragmatic metastases where liver, spleen and kidney show an increase in 111In-DTPA-octreotide. PMID:10939603

  13. Evaluation of the viability of /sup 111/In-abeled DTPA coupled to fibrinogen

    SciTech Connect

    Layne, W.W.; Hnatowich, D.J.; Doherty, P.W.; Childs, R.L.; Lanteigne, D.; Ansell, J.

    1982-07-01

    In earlier work, DTPA has been covalently coupled to albumin via the cyclic anhydride of DTPA. Using fibrinogen, we have studied the effect of such coupling on protein viability by both an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with /sup 125/I and /sup 111/In. Throughout 130 hr, blood clearances for the two tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot-to-blood ratios for the two radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with /sup 111/In, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 hr clearly showed clotting along the length of the catheter. We conclude that fibrinogen, coupled to DTPA, retains its viability, behaving like radioiodinated fibrinogen in vivo, and /sup 111/In labeled fibrinogen looks promising as a clinical diagnostic agent.

  14. Evaluation of 111In-labeled Anginex as Potential SPECT Tracer for Imaging of Tumor Angiogenesis.

    PubMed

    Van Mourik, Tiemen R; Läppchen, Tilman; Rossin, Raffaella; Van Beijnum, Judy R; Macdonald, John R; Mayo, Kevin H; Griffioen, Arjan W; Nicolay, Klaas; Grüll, Holger

    2015-11-01

    Angiogenesis is a prerequisite for solid tumors to grow and metastasize, providing oxygen and nutrients to the tumor site. The protein galectin-1 has been identified to be overexpressed on tumor vasculature and represents an interesting target for anti-angiogenic therapy, as well as in molecular imaging. Therefore, the galectin-1-binding peptide Anginex was modified for radiolabeling using (111)In. In vitro, (111)In-Ax showed significantly more binding to galectin-1-positive EC-RF24 and MDA-MB-231-LITG cells than to galectin-1-negative LS174T cells and association with EC-RF24 cells was reduced in the presence of excess native Anginex. However, ex vivo biodistribution profiles showed little tumor uptake of (111)In-Ax and extensive accumulation in non-target organs. Although this study shows the ease of modification of the therapeutic peptide Anginex and favorable characteristics in vitro, in vivo assessment of the tracer revealed negligible tumor targeting. Hence, the strategy we employed lends little support for successful non-invasive imaging of tumor angiogenesis using this peptide. PMID:26504018

  15. Radiolabeling of equine platelets in plasma with /sup 111/In-(2-mercaptopyridine-N-oxide) and their in vivo survival

    SciTech Connect

    Coyne, C.P.; Kelly, A.B.; Hornof, W.J.; O'Brien, T.R.; Philp, M.S.; Lamb, J.F.

    1987-03-01

    A method is presented for the in vitro isolation and radiolabeling of equine platelets with the isotope indium /sup 111/ (/sup 111/In: half-life = 2.8 days, gamma = 173 keV, 89%; 247 keV, 94%). The technique described involves complexing /sup 111/In with the lipid-soluble chelating agent, 2-mercaptopyridine-N-oxide (merc), in an aqueous medium. /sup 111/In-merc platelet-labeling efficiencies in autologous plasma pretreated with or without ferric citrate reagent were 82 +/- 7% and 24 +/- 12%, respectively. Mean intravascular survivals of /sup 111/In-merc-radiolabeled platelets in 8 healthy horses according to simple linear, exponential, mean, weighted-mean residual sum of squares analysis, and multiple-hit model were 5.5 +/- 0.49, 3.5 +/- 0.53, 4.5 +/- 0.18, 4.3 +/- 0.65, and 3.6 +/- 0.97 days, respectively.

  16. Use of Local {sup 111}In-Capromab Pendetide Scan Results to Predict Outcome After Salvage Radiotherapy for Prostate Cancer

    SciTech Connect

    Koontz, Bridget F. Mouraviev, Vladimir; Johnson, Jeffrey L.; Mayes, Janice; Chen, Stephanie H.; Wong, Terence Z.; Anscher, Mitchell S.; Sun, Leon; Moul, Judd; Polascik, Thomas J.

    2008-06-01

    Purpose: The {sup 111}In-capromab pendetide scan (ProstaScint; Cytogen Corp., Princeton NJ) is approved by the Food and Drug Administration to evaluate increasing prostate-specific antigen (PSA) levels after radical prostatectomy. This study evaluated the role of prostate bed {sup 111}In-capromab pendetide scan findings to predict response to salvage radiotherapy (RT). Methods and Materials: Forty patients who had PSA recurrence after radical prostatectomy and a {sup 111}In-capromab pendetide scan immediately before salvage prostate bed RT (median, 66 Gy) were identified from the Duke Prostate Center database. Patients with distant uptake of capromab pendetide or long-term androgen deprivation therapy were excluded. Median follow-up after salvage RT was 2.7 years. Patient demographic, clinical, and pathologic characteristics; PSA values; and {sup 111}In-capromab pendetide scan results were retrospectively analyzed. A PSA failure after salvage RT was defined as PSA level greater than 0.2 ng/ml. Data were combined with other published results in a secondary pooled analysis of 106 patients. Results: {sup 111}In-Capromab pendetide findings included 20 patients with negative scan results and 20 with locally positive scan results. Two-year progression-free survival rates were 60% for patients with a negative scan result and 74% for those with a locally positive scan result (p = 0.49). Combined analysis did not show a difference in outcome based on local {sup 111}In-capromab pendetide scan result. Conclusion: For patients without distant signal detected by using {sup 111}In-capromab pendetide scan, patients with locally positive scan findings did not have statistically different progression-free survival than those with a negative scan result, suggesting that salvage RT may be successful in patients with either a locally positive or negative {sup 111}In-capromab pendetide scan result.

  17. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  18. Internal radiotherapy and dosimetric study for 111In/ 177Lu-pegylated liposomes conjugates in tumor-bearing mice

    NASA Astrophysics Data System (ADS)

    Wang, Hsin-Ell; Yu, Hung-Man; Lu, Yi-Ching; Heish, Ning-Ning; Tseng, Yun-Long; Huang, Kuang-Liang; Chuang, Kuo-Tang; Chen, Chin-Hsiung; Hwang, Jeng-Jong; Lin, Wuu-Jyh; Wang, Shyh-Jen; Ting, Gann; Whang-Peng, Jacqueline; Deng, Win-Ping

    2006-12-01

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. MethodsThe DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111In/ 177Lu-(oxine) 3 to afford 111In/ 177Lu-liposome. The stability of 111In/ 177Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111In/ 177Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. ResultsThe incorporation efficiency of 111In/ 177Lu into liposomes was 95%. After incubation at 37 °C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111In/ 177Lu-liposomes. The biodistribution of 111In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of 177Lu-liposomes. Scintigraphic imaging with 111In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177Lu-liposomes was 5.74×10 -5 Gy/MBq. ConclusionsThis study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

  19. Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

    SciTech Connect

    Hanson, S.R.; Paxton, L.D.; Harker, L.A.

    1986-09-01

    To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous /sup 111/In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located /sup 111/In source implanted at the time of surgery. In five animals, /sup 111/In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of /sup 111/In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced /sup 111/In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, /sup 111/In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy.

  20. Nuclear oncology, a fast growing field of nuclear medicine

    NASA Astrophysics Data System (ADS)

    Olivier, Pierre

    2004-07-01

    Nuclear Medicine in oncology has been for a long time synonymous with bone scintigraphy, the first ever whole body imaging modality, and with treatment of thyroid cancer with iodine-131. More recently, somatostatin receptor scintigraphy (SRS) using peptides such as 111In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while 131I- and 123I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of 99mTc-labelled colloids supports, in combination with per operative detection, the procedure of sentinel node identification in breast cancers and melanomas. Positron Emission Tomography (PET) is currently experiencing a considerable growth in oncology based on the use of 18F-FDG (fluorodeoxyglucose), a very sensitive, although non-specific, tumor tracer. Development of instrumentation is crucial in this expansion of PET imaging with new crystals being more sensitive and hybrid imagers that permit to reduce the acquisition time and offer fused PET-CT images. Current developments in therapy can be classified into three categories. Radioimmunotherapy (RIT) based on monoclonal antibodies (or fragments) labelled with beta-emitters. This technique has recently made its entrance in clinical practice with a 90Y-labelled anti-CD20 antibody ( 90Y-ibritumomab tiuxetan (Zevalin ®)) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with 153Sm-EDTMP, 186Re-HEDP or 89Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with 90Y, 111In or 177Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined developments of radiopharmaceuticals and instrumentation.

  1. Radioimmunodetection in rhabdo- and leiomyosarcoma with 111In-anti-myosin monoclonal antibody complex.

    PubMed

    Planting, A; Verweij, J; Cox, P; Pillay, M; Stoter, G

    1990-02-01

    In patients with rhabdo- and leiomyosarcoma a radioimmunodiagnostic study was performed with 111In labeled F(ab) fragments of a monoclonal antibody against myosin. Eight patients with rhabdomyosarcoma and 18 patients with leiomyosarcoma were studied. Scanning was performed at 4, 24, and 48 h after administration of 74 MBeq of the antibody complex. A high uptake with a tumor:background ratio of 10:1 was observed in several patients with rhabdomyosarcoma but the results were less accurate in leiomyosarcoma. PMID:2297748

  2. Correlation between radioactivity and chemotherapeutics of the 111In-VNB-liposome in pharmacokinetics and biodistribution in rats

    PubMed Central

    Lee, Wen-Chuan; Chang, Chih-Hsien; Huang, Chih-Min; Wu, Yu-Tse; Chen, Liang-Cheng; Ho, Chung-Li; Chang, Tsui-Jung; Lee, Te-Wei; Tsai, Tung-Hu

    2012-01-01

    Background The combination of a radioisotope with a chemotherapeutic agent in a liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal vinorelbine, [111In-VNB-liposome]) has been reported to show better therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this therapeutic effect is attributable to the combination of a radioisotope with chemotherapeutics. The goal of this study was to investigate the pharmacokinetics, biodistribution, and correlation of Indium-111 radioactivity and vinorelbine concentration in the 111In-VNB-liposome. Methods The VNB-liposome and 111In-VNB-liposome were administered to rats. Blood, liver, and spleen tissue were collected to determine the distribution profile of the 111In-VNB-liposome. A liquid chromatography tandem mass spectrometry system and gamma counter were used to analyze the concentration of vinorelbine and radioactivity of Indium-111. Results High uptake of the 111In-VNB-liposome in the liver and spleen demonstrated the properties of a nanosized drug delivery system. Linear regression showed a good correlation (r = 0.97) between Indium-111 radioactivity and vinorelbine concentration in the plasma of rats administered the 111In-VNB-liposome. Conclusion A significant positive correlation between the pharmacokinetics and biodistribution of 111Indium radioactivity and vinorelbine in blood, spleen, and liver was found following administration of the 111In-VNB-liposome. The liposome efficiently encapsulated both vinorelbine and Indium-111, and showed a similar concentration-radioactivity time profile, indicating the correlation between chemotherapy and radiotherapy could be identical in the liposomal formulation. PMID:22359447

  3. Noninvasive detection of coronary thrombi with /sup 111/In platelets: concise communication

    SciTech Connect

    Bergmann, S.R.; Lerch, R.A.; Mathias, C.J.; Sobel, B.E.; Welch, M.J.

    1983-02-01

    The need for rapid, definitive identification of coronary thrombosis has been intensified by the advent of thrombolytic therapy and by interest in the role of thrombosis in the etiology of coronary artery disease. To determine whether platelet thrombi can be detected noninvasively with /sup 111/In platelets, a method was developed in which /sup 99m/Tc-tagged red blood cells were used to correct for activity within the blood attributable to platelets circulating but not associated with thrombus. In 18 dogs coronary thrombi were induced closed-chest with a copper coil introduced into the coronary artery. /sup 111/In platelets and /sup 99m/Tc RBCs were administered either before or 1 hr after induction of thrombus, and serial scintigrams obtained. Coronary thrombus was identified readily in the processed scintigrams. In six dogs, thrombolysis was achieved with intracoronary streptokinase. In each case serial scintigraphy demonstrated resolution of the clot. The dual radiotracer technique should permit serial noninvasive delineation of the temporal relationship between platelet deposition and coronary heart disease in patients, and should facilitate the evaluation of interventions designed to prevent platelet aggregation or to lyse existing thrombi.

  4. Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor.

    PubMed

    Yang, Xing; Minn, Il; Rowe, Steven P; Banerjee, Sangeeta Ray; Gorin, Michael A; Brummet, Mary; Lee, Hye Soo; Koo, Soo Min; Sysa-Shah, Polina; Mease, Ronnie C; Nimmagadda, Sridhar; Allaf, Mohamad E; Pomper, Martin G

    2015-10-20

    We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8-75.8% (n = 3) yield with specific radioactivities ranging from 118 - 1,021 GBq/μmol (3,200-27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX. PMID:26418876

  5. Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor

    PubMed Central

    Rowe, Steven P.; Banerjee, Sangeeta Ray; Gorin, Michael A.; Brummet, Mary; Lee, Hye Soo; Koo, Soo Min; Sysa-Shah, Polina; Mease, Ronnie C.; Nimmagadda, Sridhar; Allaf, Mohamad E.; Pomper, Martin G.

    2015-01-01

    We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8–75.8% (n = 3) yield with specific radioactivities ranging from 118 – 1,021 GBq/μmol (3,200–27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX. PMID:26418876

  6. 111In platelet imaging of left ventricular thrombi. Predictive value for systemic emboli

    SciTech Connect

    Stratton, J.R.; Ritchie, J.L. )

    1990-04-01

    To determine whether a positive indium 111 platelet image for a left ventricular thrombus, which indicates ongoing thrombogenic activity, predicts an increased risk of systemic embolization, we compared the embolic rate in 34 patients with positive {sup 111}In platelet images with that in 69 patients with negative images during a mean follow-up of 38 +/- 31 (+/- SD) months after platelet imaging. The positive and negative image groups were similar with respect to age (59 +/- 11 vs. 62 +/- 10 years), prevalence of previous infarction (94% vs. 78%, p less than 0.05), time from last infarction (28 +/- 51 vs. 33 +/- 47 months), ejection fraction (29 +/- 14 vs. 33 +/- 14), long-term or paroxysmal atrial fibrillation (15% vs. 26%), warfarin therapy during follow-up (26% vs. 20%), platelet-inhibitory therapy during follow-up (50% vs. 33%), injected {sup 111}In dose (330 +/- 92 vs. 344 +/- 118 microCi), and latest imaging time (greater than or equal to 48 hours in all patients). During follow-up, embolic events occurred in 21% (seven of 34) of patients with positive platelet images for left ventricular thrombi as compared with 3% (two of 69) of patients with negative images (p = 0.002). By actuarial methods, at 42 months after platelet imaging, only 86% of patients with positive images were embolus free as compared with 98% of patients with negative images (p less than 0.01).

  7. Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2.

    PubMed

    Sawada, T; Nishihara, T; Yamamoto, A; Teraoka, H; Yamashita, Y; Okamura, T; Ochi, H; Ho, J J; Kim, Y S; Hirakawa, K

    1999-10-01

    The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 11In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP. PMID:10595748

  8. 111In-BnDTPA-F3: an Auger electron-emitting radiotherapeutic agent that targets nucleolin

    PubMed Central

    2012-01-01

    Introduction The F3 peptide (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), a fragment of the human high mobility group protein 2, binds nucleolin. Nucleolin is expressed in the nuclei of normal cells but is also expressed on the membrane of some cancer cells. The goal was to investigate the use of 111In-labeled F3 peptide for Auger electron-targeted radiotherapy. Methods F3 was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy and conjugated to p-SCN-benzyl-diethylenetriaminepentaacetic acid (BnDTPA) for labeling with 111In to form 111In-BnDTPA-F3. MDA-MB-231-H2N (231-H2N) human breast cancer cells were exposed to 111In-BnDTPA-F3 and used in cell fractionation, γH2AX immunostaining (a marker of DNA double-strand breaks), and clonogenic assays. In vivo, biodistribution studies of 111In-BnDTPA-F3 were performed in 231-H2N xenograft-bearing mice. In tumor growth delay studies, 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) was administered intravenously to 231-H2N xenograft-bearing mice once weekly for 3 weeks. Results Membrane-binding of FITC-F3 was observed in 231-H2N cells, and there was co-localization of FITC-F3 with nucleolin in the nuclei. After exposure of 231-H2N cells to 111In-BnDTPA-F3 for 2 h, 1.7% of 111In added to the medium was membrane-bound. Of the bound 111In, 15% was internalized, and of this, 37% was localized in the nucleus. Exposure of 231-H2N cells to 111In-BnDTPA-F3 (1 μM, 6 MBq/μg) resulted in a dose-dependent increase in γH2AX foci and in a significant reduction of clonogenic survival compared to untreated cells or cells exposed to unlabeled BnDTPA-F3 (46 ± 4.1%, 100 ± 1.8%, and 132 ± 7.7%, respectively). In vivo, tumor uptake of 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) at 3-h post-injection was 1% of the injected dose per gram (%ID/g), and muscle uptake was 0.5%ID/g. In tumor growth delay studies, tumor growth rate was reduced 19-fold compared to untreated or unlabeled BnDTPA-F3-treated mice (p = 0.023). Conclusion 111In-BnDTPA-F3 is

  9. H4octapa-Trastuzumab: Versatile Acyclic Chelate System for 111In and 177Lu Imaging and Therapy

    PubMed Central

    Price, Eric W.; Zeglis, Brian M.; Cawthray, Jacqueline F.; Ramogida, Caterina F.; Ramos, Nicholas

    2013-01-01

    A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCNBn- H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes 111In and 177Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator DOTA. The H4octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, ~94–95%) than those based on DOTA-trastuzumab (60 min, 37 °C ~50–88%). Further, antibody integrity was better preserved in the 111In- and 177Lu-octapatrastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93–0.95 for 111In- and 177Lu-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for 111In- and 177Lu-octapa-trastuzumab compared to 111In- and 177Lu-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios. PMID:23901833

  10. Improved activity estimation with MC-JOSEM versus TEW-JOSEM in 111In SPECT

    PubMed Central

    Ouyang, Jinsong; Fakhri, Georges El; Moore, Stephen C.

    2008-01-01

    We have previously developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm, MC-JOSEM. A phantom study was performed to compare quantitative imaging performance of MC-JOSEM with that of a triple-energy-window approach (TEW) in which estimated scatter was also included additively within JOSEM, TEW-JOSEM. We acquired high-count projections of a 5.5 cm3 sphere of 111In at different locations in the water-filled torso phantom; high-count projections were then obtained with 111In only in the liver or only in the soft-tissue background compartment, so that we could generate synthetic projections for spheres surrounded by various activity distributions. MC scatter estimates used by MC-JOSEM were computed once after five iterations of TEW-JOSEM. Images of different combinations of liver∕background and sphere∕background activity concentration ratios were reconstructed by both TEW-JOSEM and MC-JOSEM for 40 iterations. For activity estimation in the sphere, MC-JOSEM always produced better relative bias and relative standard deviation than TEW-JOSEM for each sphere location, iteration number, and activity combination. The average relative bias of activity estimates in the sphere for MC-JOSEM after 40 iterations was −6.9%, versus −15.8% for TEW-JOSEM, while the average relative standard deviation of the sphere activity estimates was 16.1% for MC-JOSEM, versus 27.4% for TEW-JOSEM. Additionally, the average relative bias of activity concentration estimates in the liver and the background for MC-JOSEM after 40 iterations was −3.9%, versus −12.2% for TEW-JOSEM, while the average relative standard deviation of these estimates was 2.5% for MC-JOSEM, versus 3.4% for TEW-JOSEM. MC-JOSEM is a promising approach for quantitative activity estimation in 111In SPECT. PMID:18561679

  11. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    SciTech Connect

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

  12. Preclinical evaluation of 111In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer

    PubMed Central

    Evans-Axelsson, Susan; Vilhelmsson Timmermand, Oskar; Welinder, Charlotte; Borrebaeck, Carl AK; Strand, Sven-Erik; Tran, Thuy A; Jansson, Bo; Bjartell, Anders

    2014-01-01

    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the 111In-labeled human internalizing antibody, INCA-X (111In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of 111In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of 111In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the 111In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the 111In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer. PMID:24982817

  13. Data Evaluation Acquired Talys 1.0 Code to Produce 111In from Various Accelerator-Based Reactions

    NASA Astrophysics Data System (ADS)

    Alipoor, Zahra; Gholamzadeh, Zohreh; Sadeghi, Mahdi; Seyyedi, Solaleh; Aref, Morteza

    The Indium-111 physical-decay parameters as a β-emitter radionuclide show some potential for radiodiagnostic and radiotherapeutic purposes. Medical investigators have shown that 111In is an important radionuclide for locating and imaging certain tumors, visualization of the lymphatic system and thousands of labeling reactions have been suggested. The TALYS 1.0 code was used here to calculate excitation functions of 112/114-118Sn+p, 110Cd+3He, 109Ag+3He, 111-114Cd+p, 110/111Cd+d, 109Ag+α to produce 111In using low and medium energy accelerators. Calculations were performed up to 200 MeV. Appropriate target thicknesses have been assumed based on energy loss calculations with the SRIM code. Theoretical integral yields for all the latter reactions were calculated. The TALYS 1.0 code predicts that the production of a few curies of 111In is feasible using a target of isotopically highly enriched 112Cd and a proton energy between 12 and 25 MeV with a production rate as 248.97 MBq·μA-1 · h-1. Minimum impurities shall be produced during the proton irradiation of an enriched 111Cd target yielding a production rate for 111In of 67.52 MBq· μA-1 · h-1.

  14. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging.

    PubMed

    Shi, W; Johnston, C F; Buchanan, K D; Ferguson, W R; Laird, J D; Crothers, J G; McIlrath, E M

    1998-04-01

    A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1-octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]-octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES. PMID:9666953

  15. The in vivo behavior of granulocytes labeled with indium-111 in a canine model of pneumococcal pneumonia

    SciTech Connect

    Lichter, J.P.; Konopka, R.G.; Hartman, M.T.; Moser, K.M.; Spragg, R.G.

    1984-04-01

    Use of (/sup 111/In)granulocytes in the study of pulmonary inflammation requires study of their in vivo behavior. To study the pulmonary deposition of these cells and their ability to migrate from the capillary to the alveolus, we injected (/sup 111/In)granulocytes into dogs 24 h after the induction of a right lower lobe pneumococcal pneumonia. Using external imaging, we found rapid clearance of (/sup 111/In)granulocytes from the uninvolved lung (with a residual radioactivity of 24.5 +/- 4.2% at 4 h). In contrast, 83 +/- 12.4% of the initial radioactivity was present in inflamed lung at 4 h. Bronchoalveolar lavage fluid from the inflamed lung was more cellular than that from control lung, contained a greater fraction of polymorphonuclear leukocytes (82 +/- 4.1% versus 20 +/- 6.2%), and much greater cell-associated radioactivity (ratio of 423:1, inflamed to control). Autoradiography disclosed that this radioactivity was localized to consolidated alveoli and was not prominently distributed in arterioles or venules or in airways larger than 0.6 mm. We conclude that (/sup 111/In)granulocytes are biologically active in the setting of acute lung inflammation.

  16. Therapeutic efficacy evaluation of 111in-VNB-liposome on human colorectal adenocarcinoma HT-29/ luc mouse xenografts

    NASA Astrophysics Data System (ADS)

    Lee, Wan-Chi; Hwang, Jeng-Jong; Tseng, Yun-Long; Wang, Hsin-Ell; Chang, Ya-Fang; Lu, Yi-Ching; Ting, Gann; Whang-Peng, Jaqueline; Wang, Shyh-Jen

    2006-12-01

    The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/ luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene ( luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm 3. The uptakes of 111In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm 3. The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25 and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB ( 111In-VNB-liposome). WBAR also confirmed this result. In this study, we have demonstrated a non-invasive imaging technique with a luciferase reporter gene and BLI for evaluation of tumor treatment efficacy in vivo. The SCID mice bearing HT-29/ luc xenografts treated with 111In-VNB-liposome were shown with tumor reduction by this technique.

  17. Determining the minimum number of detectable cardiac-transplanted 111In-tropolone-labelled bone-marrow-derived mesenchymal stem cells by SPECT

    NASA Astrophysics Data System (ADS)

    Jin, Yuan; Kong, Huafu; Stodilka, Rob Z.; Wells, R. Glenn; Zabel, Pamela; Merrifield, Peter A.; Sykes, Jane; Prato, Frank S.

    2005-10-01

    In this work, we determined the minimum number of detectable 111In-tropolone-labelled bone-marrow-derived stem cells from the maximum activity per cell which did not affect viability, proliferation and differentiation, and the minimum detectable activity (MDA) of 111In by SPECT. Canine bone marrow mesenchymal cells were isolated, cultured and expanded. A number of samples, each containing 5 × 106 cells, were labelled with 111In-tropolone from 0.1 to 18 MBq, and cell viability was measured afterwards for each sample for 2 weeks. To determine the MDA, the anthropomorphic torso phantom (DataSpectrum Corporation, Hillsborough, NC) was used. A point source of 202 kBq 111In was placed on the surface of the heart compartment, and the phantom and all compartments were then filled with water. Three 111In SPECT scans (duration: 16, 32 and 64 min; parameters: 128 × 128 matrix with 128 projections over 360°) were acquired every three days until the 111In radioactivity decayed to undetectable quantities. 111In SPECT images were reconstructed using OSEM with and without background, scatter or attenuation corrections. Contrast-to-noise ratio (CNR) in the reconstructed image was calculated, and MDA was set equal to the 111In activity corresponding to a CNR of 4. The cells had 100% viability when incubated with no more than 0.9 MBq of 111In (80% labelling efficiency), which corresponded to 0.14 Bq per cell. Background correction improved the detection limits for 111In-tropolone-labelled cells. The MDAs for 16, 32 and 64 min scans with background correction were observed to be 1.4 kBq, 700 Bq and 400 Bq, which implies that, in the case where the location of the transplantation is known and fixed, as few as 10 000, 5000 and 2900 cells respectively can be detected.

  18. Noninvasive Molecular Imaging of Cell Death in Myocardial Infarction using 111In-GSAO

    PubMed Central

    Tahara, Nobuhiro; Zandbergen, H. Reinier; de Haas, Hans J.; Petrov, Artiom; Pandurangi, Raghu; Yamaki, Takayoshi; Zhou, Jun; Imaizumi, Tsutomu; Slart, Riemer H. J. A.; Dyszlewski, Mary; Scarabelli, Tiziano; Kini, Annapoorna; Reutelingsperger, Chris; Narula, Navneet; Fuster, Valentin; Narula, Jagat

    2014-01-01

    Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardiomyocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intracellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. 111In-GSAO uptake was observed within the regions of apoptosis seeking agent- 99mTc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes. PMID:25351258

  19. Optical reflectance studies of highly specular anisotropic nanoporous (111) InP membrane

    NASA Astrophysics Data System (ADS)

    Steele, J. A.; Lewis, R. A.; Sirbu, L.; Enachi, M.; Tiginyanu, I. M.; Skuratov, V. A.

    2015-04-01

    High-precision optical angular reflectance measurements are reported for a specular anisotropic nanoporous (111) InP membrane prepared by doping-assisted wet-electrochemical etching. The membrane surface morphology was investigated using scanning electron microscope imaging and revealed a quasi-uniform and self-organized nanoporous network consisting of semiconductor ‘islands’ in the sub-wavelength regime. The optical response of the nanoporous InP surface was studied at 405 nm (740 THz; UV), 633 nm (474 THz; VIS) and 1064 nm (282 THz; NIR), and exhibited a retention of basic macro-dielectric properties. Refractive index determinations demonstrate an optical anisotropy for the membrane which is strongly dependent on the wavelength of incident light, and exhibits an interesting inversion (positive anisotropy to negative) between 405 and 633 nm. The inversion of optical anisotropy is attributed to a strongly reduced ‘metallic’ behaviour in the membrane when subject to above-bandgap illumination. For the simplest case of sub-bandgap incident irradiation, the optical properties of the nanoporous InP sample are analysed in terms of an effective refractive index neff and compared to effective media approximations.

  20. Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer

    PubMed Central

    2012-01-01

    Background In single photon emission computed tomography [SPECT], high specific activity of 111In-labelled tracers will allow administration of low amounts of tracer to prevent receptor saturation and/or side effects. To increase the specific activity, we studied the effect of the buffer used during the labelling procedure: NaAc, NH4Ac, HEPES and MES buffer. The effect of the ageing of the 111InCl3 stock and cadmium contamination, the decay product of 111In, was also examined in these buffers. Methods Escalating amounts of 111InCl3 were added to 1 μg of the diethylene triamine pentaacetic acid [DTPA]- and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA]-conjugated compounds (exendin-3, octreotide and anti-carbonic anhydrase IX [CAIX] antibody). Five volumes of 2-(N-morpholino)ethanesulfonic acid [MES], 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [HEPES], NH4Ac or NaAc (0.1 M, pH 5.5) were added. After 20 min at 20°C (DTPA-conjugated compounds), at 95°C (DOTA-exendin-3 and DOTA-octreotide) or at 45°C (DOTA-anti-CAIX antibody), the labelling efficiency was determined by instant thin layer chromatography. The effect of the ageing of the 111InCl3 stock on the labelling efficiency of DTPA-exendin-3 as well as the effect of increasing concentrations of Cd2+ (the decay product of 111In) were also examined. Results Specific activities obtained for DTPA-octreotide and DOTA-anti-CAIX antibody were five times higher in MES and HEPES buffer. Radiolabelling of DTPA-exendin-3, DOTA-exendin-3 and DTPA-anti-CAIX antibody in MES and HEPES buffer resulted in twofold higher specific activities than that in NaAc and NH4Ac. Labelling of DTPA-exendin-3 decreased with 66% and 73% for NaAc and NH4Ac, respectively, at day 11 after the production date of 111InCl3, while for MES and HEPES, the maximal decrease in the specific activity was 10% and 4% at day 11, respectively. The presence of 1 pM Cd2+ in the labelling mixture of DTPA-exendin-3 in NaAc and NH4Ac

  1. Activation of 112Cd by deuteron induced reactions up to 50 MeV: An alternative for 111In production?

    NASA Astrophysics Data System (ADS)

    Hermanne, A.; Adam Rebeles, R.; Van den Winkel, P.; Tárkányi, F.; Takács, S.

    2014-11-01

    In stacked foil irradiations with an incident 50 MeV deuteron beam on highly enriched 112Cd targets, the excitation functions for 109,110g,111In and 111,110g,106Ag were determined, relative to the monitor reactions natAl(d,x)22,24Na. The results were compared to the scarce literature values on enriched Cd isotopes. Through combination of reaction cross section data on all stable Cd isotopes listed in the on-line library TENDL-2013 (calculated with the TALYS 1.4 theoretical code) a comparison with our earlier study on natCd is made. The possible production of 111In through 112Cd(d,3n), as an alternative to 112Cd(p,2n), is discussed.

  2. Assessment of effective absorbed dose of (111)In-DTPA-Buserelin in human on the basis of biodistribution rat data.

    PubMed

    Lahooti, Afsaneh; Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Tavakoli, Mohammad Bagher

    2013-04-01

    In this study, the effective absorbed dose to human organs was estimated, following intra vascular administration of (111)In-DTPA-Buserelin using biodistribution data from rats. Rats were sacrificed at exact time intervals of 0.25, 0.5, 1, 2, 4 and 24 h post injections. The Medical Internal Radiation Dose formulation was applied to extrapolate from rats to humans and to project the absorbed radiation dose for various human organs. From rat data, it was estimated that a 185-MBq injection of (111)In-DTPA-Buserelin into the human might result in an estimated absorbed dose of 24.27 mGy to the total body and the highest effective absorbed dose was in kidneys, 28.39 mSv. The promising results of this study emphasises the importance of absorbed doses in humans estimated from data on rats. PMID:22874898

  3. Formation of medical radioisotopes 111In, 117 m Sn, 124Sb, and 177Lu in photonuclear reactions

    NASA Astrophysics Data System (ADS)

    Danagulyan, A. S.; Hovhannisyan, G. H.; Bakhshiyan, T. M.; Avagyan, R. H.; Avetisyan, A. E.; Kerobyan, I. A.; Dallakyan, R. K.

    2015-06-01

    The possibility of the photonuclear production of radioisotopes 111In, 117 m Sn, 124Sb, and 177Lu is discussed. Reaction yields were measured by the gamma-activation method. The enriched tin isotopes 112, 118Sn and Te and HfO2 of natural isotopic composition were used as targets. The targets were irradiated at the linear electron accelerator of Alikhanian National Science Laboratory (Yerevan) at the energy of 40 MeV. The experimental results obtained in this way reveal that the yield and purity of radioisotopes 111In and 117 mSn are acceptable for their production via photonuclear reactions. Reactions proceeding on targets from Te and HfO2 of natural isotopic composition and leading to the formation of 124Sb and 177Lu have small yields and are hardly appropriate for the photoproduction of these radioisotopes even in the case of enriched targets.

  4. Hyperthermia enhances localization of sup 111 In-labeled hapten to bifunctional antibody in human colon tumor xenografts

    SciTech Connect

    Gridley, D.S.; Ewart, K.L.; Cao, J.D.; Stickney, D.R. )

    1991-03-01

    A unique bifunctional antibody (BFA) delivery system was examined for radiolocalization and distribution following hyperthermia (41.5 degrees C, 45 min) of T380h human colon tumor xenografts. The BFA is an F(ab')2 fragment made by combining two murine monoclonal antibodies with different specificities, one directed against carcinoembryonic antigen (monoclonal antibody CEM 231) and the other (monoclonal antibody CHA 255) against a hapten found on a derivative of 111In-labeled benzyl-EDTA (EOTUBE). This BFA is known as CEM/CHA. The CEM/CHA accumulates in carcinoembryonic antigen-expressing tissue and clears from normal tissues prior to administration of the radiolabeled hapten. T380h tumor chunks were injected s.c. into 31 nude mice. Two weeks later mean tumor volume was 352 mm3 and the animals were assigned to one of four groups: (a) CEM/CHA + hyperthermia + 111In-EOTUBE; (b) CHA 255 F(ab')2 + hyperthermia + 111In-EOTUBE, and (c and d) treated in the same manner as a and b, respectively, but without heat. The CEM/CHA, CHA 255 F(ab')2, and 111In-labeled hapten were injected i.p. at 14 micrograms, 7 micrograms, and 140-200 microCi/mouse, respectively. The hyperthermia was administered 22-24 h after BFA and the radiolabeled hapten was injected 2 h later. Twenty-four h thereafter, the animals were euthanized for testing. A significantly greater percentage of injected radioactivity localized within heated compared to unheated tumors in mice given CEM/CHA and 111In-EOTUBE (7.39%/g tumor and 4.46%/tumor versus 2.72%/g tumor and 1.44%/tumor, respectively). The percentage of kidney activity in mice given CHA 255 F(ab')2 fragments and heat was 57% lower than in the nonheated group when expressed on a per g basis (12.73 and 22.20%, respectively). Microautoradiography showed greater radiolocalization in heated tumors than in nonheated control tumors of comparable size.

  5. 111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma.

    PubMed

    Shih, Ying-Hsia; Peng, Cheng-Liang; Lee, Shin-Yu; Chiang, Ping-Fang; Yao, Cheng-Jung; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-06-30

    Colorectal adenocarcinoma is a common cause death cancer in the whole world. The aim of this study is to define the 111In-cetuximab as a diagnosis tracer of human colorectal adenocarcinoma. In this research, cell uptake, nano-SPECT/CT scintigraphy, autoradiography, biodistribution and immunohitochemical staining of EGF receptor were included. HCT-116 and HT-29 cell expressed a relatively high and moderate level of EGF receptor, respectively. The nano-SPECT/CT image of 111In-cetuximab showed tumor radiation uptake of subcutaneous HCT-116 xenograft tumor was higher than SW-620. Autoradiography image also showed that tumor of HCT-116 had high 111In-cetuximab uptake. Mice that bearing CT-26 in situ xenograft colorectal tumors showed similar high uptake in vivo and ex vivo through nano-SPECT/CT imaging at 72 hours. Metastatic HCT-116/Luc tumors demonstrated the highest uptake at 72 hours after the injection of 111In-cetuximab. Relatively, results of 111In-DTPA showed that metabolism through urinary system, especially in the kidney. The quantitative analysis of biodistribution showed count value of metastatic HCT-116/Luc tumors that treated with 111In-cetuximab had a significant difference (P < 0.05) compared with that treated with 111In-DTPA after injection 72 hours. Result of immunohistologic staining of EGF receptor also showed high EGF receptor expression and uptake in metastatic colorectal tumors. In summary, we suggested that 111In-cetuximab will be a potential tool for detecting EGF receptor expression in human metastatic colorectal carcinoma. PMID:26062654

  6. Multimodality Molecular Imaging of [18F]-Fluorinated Carboplatin Derivative Encapsulated in [111In]-Labeled Liposomes

    NASA Astrophysics Data System (ADS)

    Lamichhane, Narottam

    -(5-fluoro-pentyl)-2-methyl malonic acid as the labeling agent to coordinate with the cisplatin aqua complex. It was then used to treat various cell lines and compared with cisplatin and carboplatin at different concentrations ranging from 0.001 microM to 100 microM for 72 hrs and 96 hrs. IC50 values calculated from cell viability indicated that 19F-FCP is a more potent drug than Carboplatin. Manual radiosynthesis and characterization of [18F]-FCP was performed using [18F]-2-(5-fluoro-pentyl)-2-methyl malonic acid with coordination with cisplatin aqua complex. Automated radiosynthesis of [18F]-FCP was optimized using the manual synthetic procedures and using them as macros for the radiosynthesizer. [18F]-FCP was evaluated in vivo with detailed biodistribution studies and PET imaging in normal and KB 3-1 and KB 8-5 tumor xenograft bearing nude mice. The biodistribution studies and PET imaging of [18F]-FCP showed major uptake in kidneys which attributes to the renal clearance of radiotracer. In vivo plasma and urine stability demonstrated intact [18F]-FCP. [ 111In]-Labeled Liposomes was synthesized and physiochemical properties were assessed with DLS. [111In]-Labeled Liposome was evaluated in vivo with detailed pharmacokinetic studies and SPECT imaging. The biodistribution and ROI analysis from SPECT imaging showed the spleen and liver uptake of [111In]-Labeled Liposome and subsequent clearance of activity with time. [18F]-FCP encapsulated [111In]-Labeled Liposome was developed and physiochemical properties were characterized with DLS. [18F]-FCP encapsulated [111In]-Labeled Liposome was used for in vivo dual tracer PET and SPECT imaging from the same nanoconstruct in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice. PET imaging of [18F]-FCP in KB 3-1 (sensitive) and COLO 205 (resistant) tumor xenograft bearing nude mice was performed. Naked [18F]-FCP and [18F]-FCP encapsulated [ 111In]-Labeled Liposome showed different pharmacokinetic profiles. PET

  7. In vivo and in vitro uptake of 111In, delivered with the affibody molecule (ZEGFR:955)2, in EGFR expressing tumour cells.

    PubMed

    Nordberg, E; Orlova, A; Friedman, M; Tolmachev, V; Ståhl, S; Nilsson, F Y; Glimelius, B; Carlsson, J

    2008-04-01

    The epidermal growth factor receptor, EGFR, is overexpressed in many carcinomas. Targeting this receptor with radionuclides is important for imaging and therapy applications in nuclear medicine. We investigated the in vitro and in vivo properties of a new high affinity EGFR binding affibody molecule, (ZEGFR:955)2, when conjugated with CHX-A''-DTPA and labelled with 111In. The binding time patterns and retention studies were performed using cultured squamous carcinoma A431 cells that overexpress EGFR. In the in vivo studies, female BALB/c nu/nu mice carrying tumours from xenografted A431 cells were used. The in vitro studies showed EGFR specific binding, high uptake and good retention of 111In when delivered as [111In](ZEGFR:955)2. The retention after 72 h of incubation was 38.0+/-1.15% of the initial level. The biodistribution study showed a tumour specific 111In uptake of 3.8+/-1.4% of injected dose per gram tumour tissue 4 h post-injection. The tumour to blood ratio was 9.1 and the tumours could easily be visualized with a gamma camera at this time-point. 111In delivered with [111In](ZEGFR:955)2 gave an EGFR specific uptake and the results indicated that the (ZEGFR:955)2 affibody molecule is a candidate for radionuclide-based tumour imaging. Potential therapy applications are discussed. PMID:18357367

  8. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ

    SciTech Connect

    Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.

    1986-01-01

    Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

  9. Repeatability of Radiotracer Uptake in Normal Abdominal Organs with 111In-Pentetreotide Quantitative SPECT/CT

    PubMed Central

    Rowe, Steven P.; Vicente, Esther; Anizan, Nadège; Wang, Hao; Leal, Jeffrey P.; Lodge, Martin A.; Frey, Eric C.; Wahl, Richard L.

    2015-01-01

    With an increasing emphasis on quantitation of SPECT imaging and its use in dosimetry to guide therapies, it is desirable to understand the repeatability in normal-organ SPECT uptake values (SPECT-UVs). We investigated the variability of normal abdominal organ uptake in repeated 111In-pentetreotide SPECT studies. Methods Nine patients with multiple 111In-pentetreotide SPECT/CT studies for clinical purposes were evaluated. Volumes of interest were drawn for the abdominal organs and applied to SPECT-UVs. The variability of those values was assessed. Results The average SPECT-UV for the liver (1.7 ± 0.6) was much lower than for the kidneys (right, 8.0 ± 2.4; left, 7.5 ± 1.7). Interpatient and intrapatient variability was similar (intraclass correlation coefficients, 0.40–0.59) for all organs. The average coefficients of variation for each organ for each patient were obtained and averaged across all patients (0.26 for liver, 0.22 for right kidney, and 0.20 for left kidney). The coefficients of variation for the organs across all scans were 0.33 (liver), 0.30 (right kidney), and 0.22 (left kidney). Conclusion Variability across all patients and all scans for the liver was higher than reported with 18F-FDG PET, though left kidney variability was similar to PET liver variability and left kidney uptake may be able to serve as an internal metric for determining the quantifiability of an 111In-pentetreotide SPECT study. PMID:25977467

  10. Comparison of /sup 111/In platelet scintigraphy and two-dimensional echocardiography in the diagnosis of left ventricular thrombi

    SciTech Connect

    Ezekowitz, M.D.; Wilson, D.A.; Smith, E.O.; Burow, R.D.; Harrison, L.H. Jr.; Parker, D.E.; Elkins, R.C.; Peyton, M.; Taylor, F.B.

    1982-06-24

    In a study comparing /sup 111/In platelet scintigraphy and two-dimensional echocardiography as methods of identifying left ventricular thrombi, the results obtained with both techniques were verified at surgery or autopsy in 53 patients--34 with left ventricular aneurysms, and 19 with mitral-valve disease. Left ventricular thrombi were found at surgery or autopsy in 14 of the patients with aneurysms and in none of those with mitral-valve disease. Thirteen of 53 echocardiograms (25 per cent) were technically inadequate and excluded from the analysis. In the group with aneurysms, the sensitivity of scintigraphy in detecting thrombi was 71 per cent, and that of echocardiography was 77 per cent. The specificity of scintigraphy was 100 per cent, and that of echocardiography was 93 per cent. We conclude that /sup 111/In platelet scintigraphy and two-dimensional echocardiography have useful and complementary roles in the detection of left ventricular thrombi. Both these noninvasive techniques can be used to monitor therapy.

  11. Influence of electron capture after-effects on the stability of 111In( 111Cd)-complexes with organic ligands

    NASA Astrophysics Data System (ADS)

    Shpinkova, L. G.; Carbonari, A. W.; Nikitin, S. M.; Mestnik-Filho, J.

    2002-06-01

    The TDPAC technique was applied to verify a hypothesis about the influence of electron capture after-effects on the integrity of radiometal complexes with organic ligands in aqueous solutions. The neutral aqueous solutions of DTPA-complexes with two parent isotopes, 111In(EC) 111Cd and 111mCd, were used for direct comparison of dynamic interaction parameters. Data for the parent 111In-DTPA complexes revealed three fractions with essentially different relaxation constants, including an "unperturbed" fraction, which, according to the hypothesis, is due to small fragments of the initial complexes disintegrated as a result of Auger-process and the following Coulomb fragmentation. Only one fraction with a relaxation constant of 3(1)×10 6 s-1 was observed for the 111mCd-DTPA solution confirming the proposal about the influence of electron capture after-effects. Measurements with the frozen solutions allowed determining the electric field gradient (EFG) at Cd-sites in complexes with DTPA, V zz=6.7(2)×10 21 V/m2 with an asymmetry parameter η=0.75(5).

  12. (153)Sm(3+) and (111)In(3+) DTPA derivatives with high hepatic specificity: in vivo and in vitro studies.

    PubMed

    Prata, M I M; Santos, A C; Neves, M; Geraldes, C F G C; de Lima, J J P

    2002-07-25

    Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L(1)) and the ligand DTPA(BOM)(3) (BOM=benzyloxymethyl) (L(2)), radiolabelled with (153)Sm(3+) and (111)In(3+), were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L(2) show even greater hepatobiliary specificity than L(1), perhaps as a consequence of longer blood circulation times due to their strong affinity towards HSA. The (153)Sm(3+) chelates are also more hepatospecific than the corresponding (111)In(3+) chelates. The La(3+) and In(3+) chelates of L(1) and L(2) show some structural and dynamic differences in aqueous solution, as studied by (1)H NMR spectroscopy. While only two nona-coordinated isomers were observed for the La(3+) complexes with both ligands, its number is much larger in the In(3+) complexes, with both octa- and hepta-coordinated species (with unbound side arms), as well as structural isomers for each coordination number. PMID:12121790

  13. 111In-exendin Uptake in the Pancreas Correlates With the β-Cell Mass and Not With the α-Cell Mass

    PubMed Central

    Joosten, Lieke; Frielink, Cathelijne; Boerman, Otto; Gotthardt, Martin

    2015-01-01

    Targeting of the GLP-1 receptor with 111In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising initial results, the influence of α-cells on the uptake of the radiotracer remains a matter of debate. In this study, we determined the correlation between pancreatic tracer uptake and β- and α-cell mass in a rat model for β-cell loss. The uptake of 111In-exendin (% ID/g) showed a strong positive linear correlation with the BCM (Pearson r = 0.82). The fraction of glucagon-positive cells in the total endocrine mass was increased after alloxan treatment (26% ± 4%, 43% ± 8%, and 69% ± 21% for 0, 45, and 60 mg/kg alloxan, respectively). The uptake of 111In-exendin showed a negative linear correlation with the α-cell fraction (Pearson r = −0.76). These data clearly indicate toward specificity of 111In-exendin for β-cells and that the influence of the α-cells on 111In-exendin uptake is negligible. PMID:25409700

  14. Stability, characterization, and kinetics of /sup 111/In-labeled monoclonal antitumor antibodies in normal animals and nude mouse-human tumor models

    SciTech Connect

    Halpern, S.E.; Hagan, P.L.; Garver, P.R.; Koziol, J.A.; Chen, A.W.; Frincke, J.M.; Bartholomew, R.M.; David, G.S.; Adams, T.H.

    1983-11-01

    Monoclonal antibodies (MoAbs) against carcinoembryonic antigen were successfully radiolabeled with /sup 111/In, and the radiopharmaceutical was characterized in vitro and in normal and tumor-bearing mice. The /sup 111/In-MoAb proved to be stable in vitro and in vivo under normal conditions, although instability could be induced in vitro with large quantities of iron-free transferrin. Animal distribution studies with /sup 111/In-MoAb demonstrated tumor localization superior to /sup 67/Ga and pharmacokinetics that were highly similar to those of endogenously labeled /sup 75/Se-MoAb. The /sup 111/In-MoAb followed first-order kinetics and fit a two-compartmental model when studied in nude mice bearing human colon tumors known to express carcinoembryonic antigen. Significant quantities of radiolabel appeared in tissues other than tumor, with liver and skin having the highest concentrations. Sufficient tumor/background ratios were formed for scanning purposes. The data indicate that /sup 111/In-MoAb may prove to be effective as a radiopharmaceutical for tumor imaging.

  15. (111)In-exendin uptake in the pancreas correlates with the β-cell mass and not with the α-cell mass.

    PubMed

    Brom, Maarten; Joosten, Lieke; Frielink, Cathelijne; Boerman, Otto; Gotthardt, Martin

    2015-04-01

    Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising initial results, the influence of α-cells on the uptake of the radiotracer remains a matter of debate. In this study, we determined the correlation between pancreatic tracer uptake and β- and α-cell mass in a rat model for β-cell loss. The uptake of (111)In-exendin (% ID/g) showed a strong positive linear correlation with the BCM (Pearson r = 0.82). The fraction of glucagon-positive cells in the total endocrine mass was increased after alloxan treatment (26% ± 4%, 43% ± 8%, and 69% ± 21% for 0, 45, and 60 mg/kg alloxan, respectively). The uptake of (111)In-exendin showed a negative linear correlation with the α-cell fraction (Pearson r = -0.76). These data clearly indicate toward specificity of (111)In-exendin for β-cells and that the influence of the α-cells on (111)In-exendin uptake is negligible. PMID:25409700

  16. An experimental comparison of the K- and L-Auger electron spectra generated in the decays of 140Nd and 111In.

    PubMed

    Yakushev, E A; Kovalík, A; Filosofov, D V; Korolev, N A; Lebedev, N A; Lubashevski, A V; Rösch, F; Novgorodov, A F

    2005-03-01

    The low-energy electron spectra generated in the decay of 140Nd have been measured using a combined electrostatic spectrometer adjusted to the 4, 7, and 35 eV instrumental resolution. In order to estimate the therapeutic potential of low-energy electrons associated with the decay of 140Nd, similar experiments have been performed with 111In. Relative Auger electron intensity ratios per decay are: 111In(K-Auger)/140Nd(K-Auger)=1.47(12), 111In(L-Auger) /140Nd(L-Auger)=1.1(4), and 111In(L-Auger [2.8-7 keV])/140Nd(L-Auger [2.8-7 keV])=0.24(11). The obtained K-Auger group intensity ratios have been compared with results of calculations. The good agreement found for the experimental and estimated values indicates that such information can be also derived using available nuclear and atomic data. The relative intensity of L-Auger electrons emitted within the 2.8-7 keV interval is higher for 140Nd by a factor of about 4 compared to 111In. As the L-Auger emission is dominating relative to that of the K-Auger group, this implicates that any potential endotherapeutic strategy using 140Nd-labelled targeting vectors requires a maximum accumulation of the endoradiotherapeutical close to the cell nucleus or the DNA of the tumour cell. PMID:15607923

  17. In vivo Tumor Grading of Prostate Cancer using Quantitative 111In-Capromab Pendetide SPECT/CT

    PubMed Central

    Seo, Youngho; Aparici, Carina Mari; Cooperberg, Matthew R.; Konety, Badrinath R.; Hawkins, Randall A.

    2010-01-01

    We have developed an in vivo antibody uptake quantification method using 111In-capromab pendetide single photon emission computed tomography combined with computed tomography (SPECT/CT) technology. Our goal is to evaluate this noninvasive antibody quantification method for potential prostate tumor grading. Methods Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/ml) were calculated from uniform phantom filled with aqueous solution of 111InCl3 using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point spread function (PSF), and the PSF was implemented in a deconvolution-based partial volume error (PVE) correction algorithm. The recovery capability to correctly estimate true tracer concentration values was tested using prostate-like and bladder-like lesion phantoms fitted in the modified NEMA/IEC body phantom. Patients with biopsy-proven prostate cancer (n=10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco VA Medical Center. The CT portion of SPECT/CT was used for CT-based attenuation map generation as well as an anatomical localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo “antibody uptake value” (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of prostate gland with cylindrical volumes of interest (VOIs) having dimensions of 1.5 cm both in diameter and height. Results Reconstructed SPECT images further corrected by the deconvolution

  18. Radiolabeled red cell viability. II. /sup 99m/Tc and /sup 111/In for measuring the viability of heterologous red cells in vivo

    SciTech Connect

    Marcus, C.S.; Myhre, B.A.; Angulo, M.C.; Salk, R.D.; Essex, C.E.; Demianew, S.H.

    1987-09-01

    The authors developed a double in vivo crossmatch method using 2 to 3 ml of potential donor blood labeled with either 400 microCi of /sup 99m/Tc or 30 microCi of /sup 111/In-oxine. Data are presented for 19 crossmatches on nine patients, using one blood specimen labeled with /sup 99m/Tc or two specimens, one labeled with /sup 99m/Tc and the other with /sup 111/In. Normal values are given for standardization purposes. This method appears to have advantages over earlier in vivo crossmatch techniques using 51Cr-labeled RBCs. These advantages include the rapidity with which the in vivo crossmatch may be repeated, the ready availability of /sup 99m/Tc and /sup 111/In-oxine, and the lower radiation absorbed doses with the shorter-lived radionuclides.

  19. Kit for the preparation of (111)In-labeled pertuzumab injection for imaging response of HER2-positive breast cancer to trastuzumab (Herceptin).

    PubMed

    Lam, Karen; Scollard, Deborah A; Chan, Conrad; Levine, Mark N; Reilly, Raymond M

    2014-10-23

    We previously reported that (111)In-labeled pertuzumab imaged trastuzumab (Herceptin)-mediated changes in HER2 expression preclinically in breast cancer tumors. To advance (111)In-labeled pertuzumab to a Phase I/II clinical trial, a kit was designed for preparing this agent in a form suitable for human administration. Unit-dose kits containing pertuzumab modified with 2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (BzDTPA) were prepared that labeled to high efficiency (>90%) with (111)In and met specifications for pharmaceutical quality. The kits were stable for 4 months and the final radiopharmaceutical was stable for 24h. Imaging studies demonstrated high and specific uptake in HER2-positive tumors in mice using this clinical kit formulation. PMID:25464190

  20. Investigation of the endogenous chemoattractants involved in 111In-eosinophil accumulation in passive cutaneous anaphylactic reactions in the guinea-pig.

    PubMed Central

    Weg, V B; Watson, M L; Faccioli, L H; Williams, T J

    1994-01-01

    1. Eosinophil accumulation and plasma extravasation are features of type I allergic responses. In an attempt to characterize the mediators of these responses, we have examined the local accumulation of 111In-eosinophils and leakage of 125I-human serum albumin (125I-HSA) during passive cutaneous anaphylaxis (PCA) reactions and in response to defined inflammatory mediators in the guinea-pig. Animals were passively sensitized by intradermal injection of anti-bovine gamma globulin antibody (50 microliters, 1/50 dilution). After 20-24 h, animals were injected intravenously with 111In-eosinophils and 125I-HSA for the measurement of cell accumulation and plasma leakage, respectively. 2. When injected into sensitized sites, antigen caused a dose-related increase in the accumulation of 111In-eosinophils and plasma leakage in guinea-pig skin. Time course experiments over 24 h revealed that the maximal rate of 111In-eosinophil accumulation occurred over the first 90 min, with little accumulation at later time points. Plasma leakage was completed within the first 30 min after challenge. Responses to the mast cell degranulator, compound 48/80, exhibited very similar responses to the PCA reaction. 3. Co-injection of antigen with the PAF antagonist, WEB 2086 (10(-7) mol/site) or the 5-lipoxygenase inhibitor, PF 5901 (10(-7) mol/site) did not significantly alter the accumulation of 111In-eosinophils or plasma leakage, whereas these drug doses abolished responses to exogenous PAF (10(-9) mol/site) and arachidonic acid (AA, 3 x 10(-8) mol/site), respectively. The H1 receptor antagonist chlorpheniramine (2.5 x 10(-8) mol/site) did not reduce antigen-induced 111In-eosinophil accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812629

  1. /sup 111/In-platelet and /sup 125/I-fibrinogen deposition in the lungs in experimental acute pancreatitis

    SciTech Connect

    Goulbourne, I.A.; Watson, H.; Davies, G.C.

    1987-12-01

    An experimental model of acute pancreatitis in rats has been used to study intrapulmonary /sup 125/I-fibrinogen and /sup 111/In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. /sup 125/I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). /sup 125/I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy.

  2. Comparisons of scintigraphy with /sup 111/In leukocytes and /sup 67/Ga in the diagnosis of occult sepsis

    SciTech Connect

    Sfakianakis, G.N.; Al-Sheikh, W.; Heal, A.; Rodman, G.; Zeppa, R.; Serafini, A.

    1982-07-01

    In a prospective study involving 32 patients with clinical suspicion of focal infection, the sensitivity and specificity of /sup 111/In-labeled leukocyte (In-WBC) scintigraphy were compared with those of /sup 67/Ga scintigraphy performed 24-48 hr later. Of a total of 192 body sites studied, 26 foci of infection were diagnosed by aspiration, cultures, or chest radiographs. Indium-WBC indicated 19 (73%) true-positive (TP) and four (2.5%) false-positive (FP) foci of abnormal accretion; /sup 67/Ga had 21 (81%) TP and 15 (9%) FP. The 7/26 (27%) false-negative (FN) In-WBC scintigrams involved infection foci of more than 2-wk duration; the 5/26 (19%) FN /sup 67/Ga studies were in patients with infections manifested for less than 1 wk. The results of this study are useful in considering the indications of the two tracers.

  3. ( sup 111 In-DTPA-D-Phe sup 1 )-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: Synthesis, radiolabeling and in vitro validation

    SciTech Connect

    Bakker, W.H.; Albert, R.; Bruns, C.; Breeman, W.A.P.; Hofland, L.J.; Marbach, P.; Pless, J.; Pralet, D.; Stolz, B.; Koper, J.W.; Lamberts, S.W.J.; Visser, T.J.; Krenning, E.P. Sandoz Pharma AG, Basel )

    1991-01-01

    As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, (DTPA-D-Phe{sup 1})-octreotide (SDZ 215-811) binds more than 95% of added {sup 111}In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, (DTPA-D-Phe{sup 1})-octreotide and non-radioactive ({sup 115}In-DTPA-D-Phe{sup 1})-octreotide. The binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatosatin as well as by octreotide, suggesting specific binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated (Tyr{sup 3})-octreotide, but indium-labeled (DTPA-D-Phe{sup 1})-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

  4. [Study of distribution of 169Yb, 69Ga and 111In in tumor tissues by macroautoradiography; comparison between viable and necrotic tumor tissues].

    PubMed

    Ando, A; Doishita, K; Sanada, S; Ando, I; Hiraki, T

    1977-01-01

    The localization of 169Yb, 67Ga and 111In in tumor tissues was determined macroautoradiographically. 169Yb-citrate and 111In-citrate were injected intravenously to the rats subcutaneously transplanted Yoshida sarcoma and were injected intraperitoneally to the mice subcutaneously transplanted Ehrlich tumor. These animals were sacrificed 3, 24 and 48 hours after injection. These tumor tissues were frozen in n-hexane (-70 degrees C) cooled with dry ice-acetone. After this, these frozen tumor tissues were cut into serial thin sections (10 micron) in the cryostat (-20 degrees C). One of the slice of these sections was then placed on X-ray film and this film was developed after exposure of several days. On the other hand, next slice of these sections were then stained using the hematoxylin and eosin. From the observations of these autoradiogram and H-E stained slice, the following results were obtained. Concentration of 169Yb, 67Ga and 111In was predominant in viable tumor tissue rather than in necrotic tumor tissue, regardless of time after the administration. 67Ga and 111In were distributed uniformly in viable tumor tissue, but deposition of 169Yb was observed more avidly in viabl tumor tissue neighboring to necrotic tumor. PMID:577017

  5. Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging

    PubMed Central

    Adler, Stephen; Mena, Esther; Kurdziel, Karen; Maltzman, Julia; Wallin, Bruce; Hoffman, Kimberly; Pastan, Ira; Paik, Chang Hum; Choyke, Peter; Hassan, Raffit

    2015-01-01

    Amatuximab is a chimeric high-affinity monoclonal IgG1/k antibody targeting mesothelin that is being developed for treatment of mesothelin-expressing cancers. Considering the ongoing clinical development of amatuximab in these cancers, our objective was to characterize the biodistribution, and dosimetry of 111Indium (111In) radiolabelled amatuximab in mesothelin-expressing cancers. Between October 2011 and February 2013, six patients including four with malignant mesothelioma and two with pancreatic adenocarcinoma underwent Single Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) imaging following administration of 111In amatuximab. SPECT/CT images were obtained at 2–4 hours, 24–48 hours and 96–168 hours after radiotracer injection. In all patients, tumor to background ratios (TBR) consistently met or exceeded an uptake of 1.2 (range 1.2–62.0) which is considered the minimum TBR that can be visualized. TBRs were higher in tumors of patients with mesothelioma than pancreatic adenocarcinoma. 111In-amatuximab uptake was noted in both primary tumors and metastatic sites. The radiotracer dose was generally well-tolerated and demonstrated physiologic uptake in the heart, liver, kidneys and spleen. This is the first study to show tumor localization of an anti-mesothelin antibody in humans. Our results show that 111In-amatuximab was well tolerated with a favorable dosimetry profile. It localizes to mesothelin expressing cancers with a higher uptake in mesothelioma than pancreatic cancer. PMID:25756664

  6. Biodistribution and pharmacokinetics of111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies

    PubMed Central

    Harrington, K J; Rowlinson-Busza, G; Syrigos, K N; Uster, P S; Abra, R M; Stewart, J S W

    2000-01-01

    The biodistribution and pharmacokinetics of111In-DTPA-labelled pegylated liposomes in tumour-bearing nude mice was studied to examine possible applications of pegylated liposome-targeted anti-cancer therapies. Nude mice received an intravenous injection of 100 μl of111In-DTPA-labelled pegylated liposomes, containing 0.37–0.74 MBq of activity. The t 1/2α and t 1/2β of111In-DTPA-labelled pegylated liposomes were 1.1 and 10.3 h, respectively. Tumour uptake was maximal at 24 h at 5.5 ± 3.0% ID g–1. Significant reticuloendothelial system uptake was demonstrated with 19.3 ± 2.8 and 18.8 ± 4.2% ID g–1at 24 h in the liver and spleen, respectively. Other sites of appreciable deposition were the kidney, skin, female reproductive tract and to a lesser extent the gastrointestinal tract. There was no indication of cumulative deposition of pegylated liposomes in the lung, central nervous system, musculoskeletal system, heart or adrenal glands. In contrast, the t 1/2α and t 1/2β of unencapsulated111In-DTPA were 5 min and 1.1 h, respectively, with no evidence of accumulation in tumour or normal tissues. Incubation of111In-DTPA-labelled pegylated liposomes in human serum for up to 10 days confirmed that they are very stable, with only minor leakage of their contents. The potential applications of pegylated liposomes in the arena of targeted therapy of solid cancers are discussed. © 2000 Cancer Research Campaign PMID:10901376

  7. Nonstoichiometric zinc oxide and indium-doped zinc oxide: Electrical conductivity and {sup 111}In-TDPAC studies

    SciTech Connect

    Wang, R.; Sleight, A.W.; Platzer, R.; Gardner, J.A.

    1996-02-15

    Indium-doped zinc oxide powders have been prepared which show room-temperature electrical conductivities as high as 30 {Omega}{sup {minus}1} cm{sup {minus}1}. The indium doping apparently occurs as Zn{sub 1-x}In{sub x}O,Zn{sub 1-y}In{sub y}O{sub 1+y/2}, or a combination of these. Optimum conductivity occurs for Zn{sub 1-x}In{sub x}O where the maximum value of x obtained was about 0.5 at%. The degrees of sample reduction were determined by iodimetric titration. Time differential perturbed angular correlation (TDPAC) spectroscopy on indium doped zinc oxide is consistent with indium substituting at normal zinc sites in the ZnO lattice. TDPAC studies on zinc oxide annealed under zinc vapors show a second environment for the {sup 111}In probe. In this case, there is an unusually high temperature dependence of the electric field gradient which may be caused by a nearby zinc interstitial. An important conclusion of this work is that zinc interstitials are not ionized and do not therefore contribute significantly to the increased conductivity of reduced zinc oxide.

  8. [Clinical trial of 111In-antimyosin antibody imaging: (3) Comparison with 99mTc-pyrophosphate imaging].

    PubMed

    Tamaki, N; Yamada, T; Matsumori, A; Fujita, T; Ohtani, H; Watanabe, Y; Yonekura, Y; Endo, K; Konishi, J; Kawai, C

    1989-09-01

    Clinical value of 111In-antimyosin monoclonal antibody F ab (AM) was compared with 99mTc-pyrophosphate (PYP) in 13 patients with myocardial infarction and 3 patients with myocarditis. Following PYP injection, PYP imaging was performed 3 hours later. Immediately after PYP imaging, AM was administrated and AM images were obtained 48 hours later. Abnormal accumulation in the infarcted myocardium was observed in 11 patients (85%) on AM images but only in 3 patients (23%) on PYP images. All patients within 8 days after the onset of infarction showed abnormal uptake on both images. Of 5 patients with 1 to 2 weeks after the onset of infarction, abnormal uptake was observed in all of them on AM images but only in one of them on PYP imaging. Furthermore, of 6 patients with more than 2 weeks after the onset, AM imaging showed abnormal uptake in 4 (67%) but PYP imaging did not show abnormal uptake in any of them. Similarly. Of 3 patients with myocarditis, diffuse uptake in the myocardium ws observed in 2 of them on AM images but none of them showed abnormal uptake on PYP images. We conclude that AM imaging is a useful means for identifying not only acute stages but also subacute stages of myocardial necrosis where PYP imaging did not show any abnormality. PMID:2554037

  9. Location and activity of ulcerative and Crohn's colitis by /sup 111/In leukocyte scan. A prospective comparison study

    SciTech Connect

    Stein, D.T.; Gray, G.M.; Gregory, P.B.; Anderson, M.; Goodwin, D.A.; McDougall, I.R.

    1983-02-01

    A prospective blinded study comparing the /sup 111/In leukocyte scan to barium enema, colonoscopy, or surgery or a combination of these, was carried out in 15 patients (10 with active ulcerative colitis and 5 with active Crohn's colitis). Correlation of disease location to colonic regions between indium scan and other diagnostic studies was excellent in 11 instances, good in 2, and poor in 3. In 2 of the 3 studies where major disagreement occurred, the comparative barium enema was performed greater than 2 mo after the indium scan. Disease activity, estimated by the intensity of radionuclide uptake, was compared to clinical disease activity assessed by the Crohn's Disease Activity Index for both forms of colitis. The relative degree of inflammation estimated by the indium scan correlated well with the independent clinical assessment (correlation coefficient . 0.81). The indium 111 leukocyte scan appears to be an accurate, noninvasive method for assessing the extent and the severity of the inflammation in patients with acute ulcerative or Crohn's colitis.

  10. A quantitative method to measure human platelet chemotaxis using /sup 111/In-oxine-labeled gel-filtered platelets

    SciTech Connect

    Lowenhaupt, R.W.; Silberstein, E.B.; Sperling, M.I.; Mayfield, G.

    1982-12-01

    Human blood platelets have been shown to migrate directionally and specifically toward collagen in plasma in vitro. We have developed a new system to monitor this behavior using a linear 7-compartment chamber with /sup 111/In-oxine-labeled gel-filtered platelets. The compartments are separated by various Nuclepore and Millipore filter membranes. Radiolabeled platelets suspended in plasma are placed in the central compartment and the other compartments are filled with platelet-free plasma. When collagen is added to an end compartment, platelets migrate toward that end. The degree of this directed movement or chemotaxis can be measured by counting the radioactivity of the contents of each compartment and then comparing the counts from radiolabeled platelets that have moved to the end that holds the chemotactic inducer with those that have randomly migrated to the opposite end, containing only plasma. This assay system allows quantitative comparisons between the chemotaxis-inducing abilities of different substances and permits the study of soluble materials. Experiments to determine the optimal conditions for the procedure are reported, and the advantages of this new method for the investigation of platelet chemotaxis and the identification of chemotaxins are discussed.

  11. Human biodistribution of [111In]diethylenetriaminepentaacetic acid-(DTPA)-D-[Phe1]-octreotide and peroperative detection of endocrine tumors.

    PubMed

    Ohrvall, U; Westlin, J E; Nilsson, S; Wilander, E; Juhlin, C; Rastad, J; Akerström, G

    1995-12-01

    Requisites for preoperative and intraoperative tumor localization with [111In]diethylenetriaminepentaacetic acid-D-[Phe1]-octreotide scanning were explored in 23 patients with endocrine tumors (15 carcinoids, 4 insulinomas, and single cases of gastrinoma, medullary thyroid carcinoma, aldosteronoma, and paraganglioma). The patients were subjected to Octreoscan single photon emission computed tomographic examination prior to surgery and well counter investigation of nuclide uptake in tumors and normal tissues sampled at surgery. Somatostatin receptor-positive tumors demonstrated efficient nuclide accumulation with mean tumor:blood radioactivity ratios of 180-370 (for carcinoids and insulinoma), compared with tissue:blood ratios of 302 for spleen, 42 for liver, and < 10-15 in other normal tissues (pancreas, small intestine, and mesenteric fat). Inefficient preoperative visualization of lesions was related to inconspicuous size, as for primary intestinal carcinoids, tiny liver metastases, and a single small insulinoma. High background activity, pronounced tumor fibrosis, and meager accumulation of tracer also interfered with visualization. Tumor deposits in organs with low background activity (such as carcinoid mesenteric metastases and endocrine pancreatic tumors) were generally most readily detected. Intraoperative investigations with hand-held gamma detector probes were disturbed by obvious high background activity. These investigations revealed two preoperatively unrecognized primary intestinal carcinoids, which, however, were both palpable during surgery. These studies, therefore, had little impact on the surgical strategy. PMID:7493348

  12. High resolution electrochemical STM : new structural results for underpotentially deposited Cu on Au(111) in acid sulfate solution.

    SciTech Connect

    Sieradzki, Karl; Vasiljevic, Natasa; Viyannalage, L.K.T.; Dimitrov, Nikolay

    2007-09-01

    Adsorption of sulfate assists Cu monolayer underpotential deposition (upd) on Au(111) in a unique way, rendering two distinct structural stages: (i) formation of a low-density Cu phase at coverage of 2/3 ML known as the ({radical}3 x {radical}3) R30{sup o} or honeycomb phase; (ii) formation of a complete monolayer, i.e., Cu-(1 x 1) phase pseudomorphic with respect to underlying Au(111) substrate. In this paper we present new structural in situ scanning tunneling microscopy (STM) results for this system. We show and discuss the STM imaging of the copper honeycomb superstructure probed underneath the co-adsorbed ({radical}3 x {radical}3)R30{sup o} sulfate adlayer in the low-density phase. High resolution imaging during the phase transition from the low to high density copper phase unambiguously shows the existence of an ordered sulfate structure p(2 x 2) on the pseudomorphic Cu-(1 x 1) layer. The new structure is seen during the co-existence of two copper phases as well as upon completion of the Cu-(1 x 1) monolayer. While supported by earlier chronocoulometric measurements in the same system, the new structural results raise questions that need to be addressed in a future work.

  13. Simultaneous administration of 111In-human immunoglobulin and 99mTc-HMPAO labelled leucocytes in inflammatory bowel disease.

    PubMed

    Mairal, L; de Lima, P A; Martin-Comin, J; Baliellas, C; Xiol, X; Roca, M; Ricart, Y; Ramos, M

    1995-07-01

    Technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocytes and indium-111 polyclonal immunoglobulin (IgG) were simultaneously injected into a group of 27 patients routinely referred for the investigation of inflammatory bowel disease (IBD). Ten-minute anterior abdomen and tail on detector views were obtained at 30 min, 4 h and 24 h p.i. of both tracers. The diagnosis of IBD was obtained in all cases by endoscopy with biopsy and/or surgery. Images were blindly evaluated by two experienced observers who only knew of the clinical suspicion of IBD. IBD was confirmed in 20 patients (12 with Crohn's disease and eight with ulcerative colitis). Sensitivity, specificity and accuracy were 100%, 85% and 96% respectively for labelled leucocytes and 70%, 85% and 74% for IgG. Both IgG and leucocyte scans were normal in six out of seven patients in whom a diagnosis of IBD was excluded; the remaining patient, with ischaemic colitis, was falsely positive with both agents. As far as disease extension is concerned, the IgG study localized 27 diseased segments, whereas 49 were seen with the leucocyte study. Eighty-four segments were normal and 25 showed tracer uptake with both agents. Twenty-four were positive only with the leucocyte study and two were positive only with the IgG study. Agreement between the agents was 80.7%. These results confirm that 111In-human polyclonal scintigraphy is less sensitive than 99mTc-HMPAO scintigraphy both for the diagnosis of IBD and in the evaluation of disease extension. Nevertheless, if leucocyte labelling is not available, labelled IgG can be used only for diagnostic purposes. PMID:7498228

  14. Immunoscintigraphic detection of venous thrombosis of the lower extremities by means of human antifibrin monoclonal antibodies labeled with sup 111 In

    SciTech Connect

    Lusiani, L.; Zanco, P.; Visona, A.; Breggion, G.; Pagnan, A.; Ferlin, G. )

    1989-07-01

    A new monoclonal antibody specific for the beta-chain of human fibrin (C22A) and labeled with 111In has been obtained and successfully used in rabbits and dogs for the in vivo detection of venous thrombosis. Studies in humans are currently ongoing. In order to assess the diagnostic value of 111In-antifibrin for the detection of venous thrombosis of the lower extremities, the authors investigated 25 consecutive patients. Ten patients had clinical and instrumental (contrast phlebography and duplex scanning) evidence of acute deep venous thrombosis (DVT), 3 had a long-standing DVT with relapsing episodes of swelling and pain, 5 had superficial venous thrombosis, and the remaining 7 had no signs of thrombosis at all. Twenty patients were being treated with heparin. All patients received 111In-antifibrin at the dose of 74 MBq IV and were scanned with a large field of view gamma camera coupled with a high-energy, parallel-hole collimator at 30 minutes and three, six, and twenty-four hours postinjection. Only the persistence of an abnormal uptake at twenty-four hours confirmed by two observers at visual inspection was considered as positive. A positive result was obtained in 9 of 10 DVT patients (90% sensitivity) and in all SVT patients. The single DVT patient with a negative 111In-antifibrin test had the longest interval between scintigraphy and onset of symptoms (fifty-five days). Thus, the age of thrombi represented a substantial limitation for the test. A false-positive result was obtained in a single SVT patient, in whom also a deep involvement, unconfirmed by phlebography, was suspected (91.6% specificity).

  15. Comparison of normal tissue pharmacokinetics with {sup 111}In/{sup 9}Y monoclonal antibody m170 for breast and prostate cancer

    SciTech Connect

    Lehmann, Joerg; O'Donnell, Robert T.; Richman, Carol M. . E-mail: sjdenardo@ucdavis.edu

    2006-11-15

    Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: {sup 111}In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and {sup 111}In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for {sup 9}Y was calculated using {sup 111}In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies.

  16. Radiolabeled red cell viability. I. Comparison of /sup 51/Cr, /sup 99m/Tc, and /sup 111/In for measuring the viability of autologous stored red cells

    SciTech Connect

    Marcus, C.S.; Myhre, B.A.; Angulo, M.C.; Salk, R.D.; Essex, C.E.; Demianew, S.H.

    1987-09-01

    The simultaneous determination of autologous /sup 99m/Tc red cell (RBC) and /sup 51/Cr RBC viability at 24 hours was measured in 19 normal volunteers whose RBCs had been stored in additive media (Nutracel) for 42 or 49 days. The ratio of the /sup 51/Cr:/sup 99m/Tc value was 1.23. In this experiment we also calculated /sup 51/Cr RBC viability by both the single-isotope method (extrapolation) and the double-isotope method (using /sup 125/I human serum albumin for an independent plasma volume) in the same volunteers. The corresponding viability values were not significantly different. The simultaneous determination of autologous /sup 111/In-oxine RBC and /sup 51/Cr RBC viability at 24 hours was measured in 19 other normal volunteers whose RBCs had been stored in citrate-phosphate-dextrose-adenine (CPDA-1) for 1 or 15 days. The ratio of the /sup 51/Cr:/sup 111/In value was 1.1. Use of these 24-hour viability ratios as conversion factors permits direct comparison of /sup 99m/Tc or /sup 111/In RBC viability with a /sup 51/Cr standard, and therefore expands the application of these newer RBC radiolabels.

  17. Comparison of Residence Time Estimation Methods for Radioimmunotherapy Dosimetry and Treatment Planning—Monte Carlo Simulation Studies

    PubMed Central

    He, Bin; Wahl, Richard L.; Du, Yong; Sgouros, George; Jacene, Heather; Flinn, Ian; Frey, Eric C.

    2008-01-01

    Estimating the residence times in tumor and normal organs is an essential part of treatment planning for radioimmunotherapy (RIT). This estimation is usually done using a conjugate view whole body scan time series and planar processing. This method has logistical and cost advantages compared to 3-D imaging methods such as Single photon emission computed tomography (SPECT), but, because it does not provide information about the 3-D distribution of activity, it is difficult to fully compensate for effects such as attenuation and background and overlapping activity. Incomplete compensation for these effects reduces the accuracy of the residence time estimates. In this work we compare residence times estimates obtained using planar methods to those from methods based on quantitative SPECT (QSPECT) reconstructions. We have previously developed QSPECT methods that provide compensation for attenuation, scatter, collimator-detector response, and partial volume effects. In this study we compared the use of residence time estimation methods using QSPECT to planar methods. The evaluation was done using the realistic NCAT phantom with organ time activities that model 111In ibritumomab tiuxetan. Projection data were obtained using Monte Carlo simulations (MCS) that realistically model the image formation process including penetration and scatter in the collimator-detector system. These projection data were used to evaluate the accuracy of residence time estimation using a time series of QSPECT studies, a single QSPECT study combined with planar scans and the planar scans alone. The errors in the residence time estimates were <3.8%, <15%, and 2%–107% for the QSPECT, hybrid planar/QSPECT, and planar methods, respectively. The quantitative accuracy was worst for pure planar processing and best for pure QSPECT processing. Hybrid planar/QSPECT methods, where a single QSPECT study was combined with a series of planar scans, provided a large and statistically significant improvement

  18. Imaging of bronchial carcinoid tumors associated to Cushing syndrome with 111In-Octreoscan scintigraphy and immunoscintigraphy with anti-chromogranin monoclonal antibodies. Report of two cases.

    PubMed

    Carretta, A; Chiesa, G; Magnani, P; Songini, C; Melloni, G; Zannini, P; Grossi, A

    1997-04-01

    Bronchial carcinoid tumors are neuroendocrine neoplasms capable of expressing somatostatin receptors and of secreting neuromediators such as ACTH and chromogranins. Radiologic appearance is usually non-specific and has to be distinguished from benign pulmonary nodules and other malignant diseases. Standard radiological techniques have limited accuracy in the evaluation of such lesions. Radioisotopic imaging techniques may increase the specificity of diagnostic assessment. The role of immunoscintigraphy with anti-chromogranin A and B monoclonal antibodies (MoAbs) and of 111In-Octreoscan scintigraphy is evaluated in two cases of bronchial carcinoid tumors associated to Cushing syndrome. PMID:9201136

  19. Isolation and (111)In-Oxine Labeling of Murine NK Cells for Assessment of Cell Trafficking in Orthotopic Lung Tumor Model.

    PubMed

    Malviya, Gaurav; Nayak, Tapan; Gerdes, Christian; Dierckx, Rudi A J O; Signore, Alberto; de Vries, Erik F J

    2016-04-01

    A noninvasive in vivo imaging method for NK cell trafficking is essential to gain further understanding of the pathogenesis of NK cell mediated immune response to the novel cancer treatment strategies, and to discover the homing sites and physiological distribution of NK cells. Although human NK cells can be labeled for in vivo imaging, little is known about the murine NK cell labeling and its application in animal models. This study describes the isolation and ex vivo radiolabeling of murine NK cells for the evaluation of cell trafficking in an orthotopic model of human lung cancer in mice. Scid-Tg(FCGR3A)Blt transgenic SCID mice were used to isolate NK cells from mouse splenocytes using the CD49b (DX5) MicroBeads positive selection method. The purity and viability of the isolated NK cells were confirmed by FACS analysis. Different labeling buffers and incubation times were evaluated to optimize (111)In-oxine labeling conditions. Functionality of the radiolabeled NK cell was assessed by (51)Cr-release assay. We evaluated physiological distribution of (111)In-oxine labeled murine NK cells in normal SCID mice and biodistribution in irradiated and nonirradiated SCID mice with orthotopic A549 human lung tumor lesions. Imaging findings were confirmed by histology. Results showed that incubation with 0.011 MBq of (111)In-oxine per million murine NK cells in PBS (pH 7.4) for 20 min is the best condition that provides optimum labeling efficiency without affecting cell viability and functionality. Physiological distribution in normal SCID mice demonstrated NK cells homing mainly in the spleen, while (111)In released from NK cells was excreted via kidneys into urine. Biodistribution studies demonstrated a higher lung uptake in orthotopic lung tumor-bearing mice than control mice. In irradiated mice, lung tumor uptake of radiolabeled murine NK cells decreased between 24 h and 72 h postinjection (p.i.), which was accompanied by tumor regression, while in nonirradiated mice

  20. Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of /sup 75/Se-, /sup 111/In-, and /sup 125/I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice

    SciTech Connect

    Koizumi, M.; Endo, K.; Watanabe, Y.; Saga, T.; Sakahara, H.; Konishi, J.; Yamamuro, T.; Toyama, S.

    1989-04-01

    In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating (75Se)methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

  1. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

    PubMed

    Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

    2005-01-01

    Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids. PMID:15816375

  2. Delineation of the structural and functional role of Arg111 in GSTU4-4 from Glycine max by chemical modification and site-directed mutagenesis.

    PubMed

    Labrou, Nikolaos E; Muharram, Magdy Mohamed; Abdelkader, Maged Saad

    2016-10-01

    The structural and functional role of Arg111 in GSTU4-4 from Glycine max (GmGSTU4-4) was studied by chemical modification followed by site-directed mutagenesis. The arginine-specific reagent 2,3-butanedione (BTD) inactivates the enzyme in borate buffer at pH8.0, with pseudo-first-order saturation kinetics. The rate of inactivation exhibited a non-linear dependence on the concentration of BTD which can be described by reversible binding of reagent to the enzyme (KD 81.2±9.2mM) prior to the irreversible reaction, with maximum rate constants of 0.18±0.01min(-1). Protection from inactivation was afforded by substrate analogues demonstrating the specificity of the reaction. Structural analysis suggested that the modified residue is Arg111, which was confirmed by protein chemistry experiments. Site-directed mutagenesis was used in dissecting the role of Arg111 in substrate binding, specificity and catalytic mechanism. The mutant Arg111Ala enzyme exhibited unchanged Km value for GSH but showed reduced affinity for the xenobiotic substrates, higher kcat and specific activities towards aromatic substrates and lower specific activities towards aliphatic substrates. The biological significance of the specific modification of Arg111 by dicarbonyl compounds and the role of Arg111 as a target for engineering xenobiotic substrate specificity were discussed. PMID:27375050

  3. In vivo application of ( sup 111 In-DTPA-D-Phe sup 1 )-octreotide for detection of somatostatin receptor-positive tumors in rats

    SciTech Connect

    Bakker, W.H.; Krenning, E.P.; Reubi, J.C.; Breeman, W.A.P.; Setyono-Han, B.; de Jong, M.; Kooij, P.P.M.; Bruns, C.; van Hagen, P.M.; Marbach, P.; Visser, T.J.; Pless, J.; Lamberts, S.W.J. Sandoz Research Inst., Berne Dr. Daniel den Hoed Cancer Centre, Rotterdam Sandoz Pharma AG, Basel )

    1991-01-01

    In this study the authors investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of ({sup 111}In-DPTA-D-Phe{sup 1})-octreotide in the tumors was prevented. Because of its relatively long effective half-life, ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance.

  4. Kinetics of leukocyte sequestration in the lungs of acutely septic primates: A study using sup 111 In-labeled autologous leukocytes

    SciTech Connect

    Hangen, D.H.; Segall, G.M.; Harney, E.W.; Stevens, J.H.; McDougall, I.R.; Raffin, T.A. )

    1990-03-01

    To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans ({sup 111}In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fall in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS.

  5. Pharmacokinetics of the monoclonal antibody B72. 3 and its fragments labeled with either /sup 125/I or /sup 111/In

    SciTech Connect

    Brown, B.A.; Comeau, R.D.; Jones, P.L.; Liberatore, F.A.; Neacy, W.P.; Sands, H.; Gallagher, B.M.

    1987-02-15

    A comparison of the pharmacokinetics of intact B72.3 (a murine monoclonal antibody specific for human breast and colon carcinoma) with F(ab')2 and Fab fragments labeled with /sup 111/In and /sup 125/I was done in athymic mice bearing target (LS174T) and non-target (HCT-15) tumors. IgG B72.3 labeled with either isotype imaged LS174T. Biodistributions of both labels were similar in all organs except liver. F(ab')2 also imaged the LS174T tumor, while Fab bearing either isotype did not. The blood clearance was Fab greater than F(ab')2 greater than immunoglobulin G B72.3 for both isotopes. /sup 111/In-labeled fragments yielded large accumulations in the kidneys which persisted for 2 days. The different patterns of biodistribution for the various forms of B72.3 labeled with the two isotopes suggest that the most desirable combination of fragment and isotope will depend on the intended use.

  6. Formation of medical radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu in photonuclear reactions

    SciTech Connect

    Danagulyan, A. S.; Hovhannisyan, G. H. Bakhshiyan, T. M.; Avagyan, R. H.; Avetisyan, A. E.; Kerobyan, I. A.; Dallakyan, R. K.

    2015-06-15

    The possibility of the photonuclear production of radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu is discussed. Reaction yields were measured by the gamma-activation method. The enriched tin isotopes {sup 112,} {sup 118}Sn and Te and HfO{sub 2} of natural isotopic composition were used as targets. The targets were irradiated at the linear electron accelerator of Alikhanian National Science Laboratory (Yerevan) at the energy of 40 MeV. The experimental results obtained in this way reveal that the yield and purity of radioisotopes {sup 111}In and {sup 117}mSn are acceptable for their production via photonuclear reactions. Reactions proceeding on targets from Te and HfO{sub 2} of natural isotopic composition and leading to the formation of {sup 124}Sb and {sup 177}Lu have small yields and are hardly appropriate for the photoproduction of these radioisotopes even in the case of enriched targets.

  7. Distribution of In-111 in granulocyte and other cellular elements of blood (CEB) in human In-111-labeled mixed white cell (MWC) and platelet preparations

    SciTech Connect

    Dewanjee, M.K.; Chowdhury, S.; Brown, M.L.; Wahner, H.W.

    1984-01-01

    A large number of platelets (PLT), red blood cells (RBC) are present along with granulocyte (GC) in In-111 in CEB was determined by Ficoll-Hypaque gradient (FHG) centrifugation of In-111-MWC and PLT preparation as a quality control procedure. MWC were separated by sedimentation with hydroxyethyl starch; PLT by differential centrifugation. MWC and PLT were labeled with In-111-oxine in saline, ACD-saline or with In-111-tropolone in 0.5 ml of ACD-plasma. 0.3-0.5 ml of labeled cell suspended in plasma was layered on 3 ml FHG of two densities (1.119 and 1.077 gm/ml) and spun in a clear polystyrene tube at 1800 G for 30 min. Four layers (plasma, PLT, GC, and RBC) were separated, and In-111 radioactivity in each fraction was determined with a gamma counter. Simultaneously cell types in MWC and PLT preparations were determined by Coulter counter and differential counting. Most of In-111 in In-MWC is associated with the PLT and RBC, GC/lymphocyte ratio is 6/4. GC has higher extraction efficiency than RBC and PLT. PLT preparation is pure and (96 +- 3)% of In-111 is bound to PLT, (4 +- 3)% to RBC and (0.2 +- 0.1)% to GC; PLT preparation contains PLT (97 +- 3)%, RBC (4 +- 3)% and GC (0.2 +- 0.1)%.

  8. Radiobiological Optimization of Combination Radiopharmaceutical Therapy Applied to Myeloablative Treatment of Non-Hodgkin’s Lymphoma

    PubMed Central

    Hobbs, Robert F; Wahl, Richard L; Frey, Eric C; Kasamon, Yvette; Song, Hong; Huang, Peng; Jones, Richard J; Sgouros, George

    2014-01-01

    Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid ‘90s, such treatment strategies have only been implemented clinically recently, and without a rigorous methodology for treatment optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiological normal organ tolerance while optimizing the ratio of two different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-hodgkin’s lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods The range of potential administered activities (AA) is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normal organ constraints as a function of the AAs and calculating tumor biological effective dose (BED) along the normal organ MTBED limits, the optimal combination of activities is obtained. The model was tested using previously acquired patient normal organ and tumor kinetic data and MTBED values taken from the literature. Results The average AA values based solely on normal organ constraints was (19.0 ± 8.2) GBq with a range of 3.9 – 36.9 GBq for 131I-tositumomab, and (2.77 ± 1.64) GBq with a range of 0.42 – 7.54 GBq for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal organ kinetics for the two radiopharmaceuticals. Results included AA ranges

  9. In vitro and in vivo comparison of human Escherichia coli heat-stable peptide analogues incorporating the 111In-DOTA group and distinct linker moieties.

    PubMed

    Giblin, Michael F; Gali, Hariprasad; Sieckman, Gary L; Owen, Nellie K; Hoffman, Timothy J; Forte, Leonard R; Volkert, Wynn A

    2004-01-01

    Three human Escherichia coli heat-stable peptide (STh) analogues, each containing a DOTA chelating group, were synthesized by SPPS and oxidative refolding and compared in in vitro and in vivo systems. One analogue, DOTA-F19-STh(1-19), contains an N-terminal DOTA group attached via an amide bond linkage to an STh moiety which is essentially wild-type except for a Tyr to Phe alteration at position 19 of the molecule. A second analogue, DOTA-R1,4,F19-STh(1-19), differs from the first in that asparagine residues in positions 1 and 4 have been altered to arginine residues in order to examine the effect of positively charged groups in the linker domain. A third analogue, DOTA-11AUN-F19-STh(1-19), differs from the first in that it incorporates an 11-aminoundecanoic acid spacer group between the DOTA group and the first asparagine residue. In vitro competitive binding assays utilizing T-84 human colon cancer cells demonstrated that significant alterations to the N-terminal region of the STh molecule were well tolerated and did not significantly affect binding affinity of STh for the guanylyl cyclase C (GC-C) receptor. Internalization and efflux studies of the indium-labeled species demonstrated that inclusion of positive charge in the linker moiety inhibits internalization of the compound within tumor cells. The characteristics of the three analogues were compared in an in vivo model utilizing T-84 human colon cancer cell xenografts in SCID mice. Clearance of all analogues was rapid, primarily via renal excretion into the urine, with >89% ID excreted into the urine at 1 h pi for all analogues. The 111In-DOTA-R1,4,F19-STh(1-19) and 111In-DOTA-11AUN-F19-STh(1-19) analogues both had longer residence times in the blood than did the 111In-DOTA-F19-STh(1-19) analogue, probably accounting for increased %ID/g values for tumors and nontarget tissues at 1 h pi. At 4 h pi, significant differences between analogues were only seen with respect to metabolic routes of excretion

  10. 111In- and 203Pb-Labeled Cyclic RGD Peptide Conjugate as an αvβ3 Integrin-Binding Radiotracer

    PubMed Central

    Nwe, Kido; Kim, Young-Seung; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2012-01-01

    Methodology for site-specific modification and chelate conjugation of a cyclic RGD (cRGD) peptide for the preparation of a radiotracer molecular imaging agent suitable for detecting αvβ3 integrin is described. The method involves functionalizing the peptide with an aldehyde moiety and conjugation to a 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) derivative that possesses an aldehyde reactive aminooxy group. The binding assay of the 111In-labeled peptide conjugate with αvβ3 integrin showed 60% bound when four equivalents of the integrin was added, a reasonable binding affinity for a mono-valent modified RGD peptide. PMID:23162207

  11. Localization of /sup 111/In- and /sup 125/I-labeled monoclonal antibody in guinea pigs bearing line 10 hepatocarcinoma tumors

    SciTech Connect

    Bernhard, M.I.; Hwang, K.M.; Foon, K.A.; Keenan, A.M.; Kessler, R.M.; Frincke, J.M.; Tallam, D.J.; Hanna, M.G. Jr.; Peters, L.; Oldham, R.K.

    1983-09-01

    A murine monoclonal antibody (D3) with demonstrated specificity for the guinea pig line 10 hepatocarcinoma (L10) was radiolabeled with either /sup 125/I or /sup 111/In and used to image dermal tumors in vivo. In one set of experiments, L10 tumors were established middorsally in one group of animals, and the similarly derived, antigenically distinct line 1 tumor was established in another group of animals. In spite of background imaging of liver, kidney, and spleen, L10 tumors were visualized clearly. Incorporation of radiolabel was demonstrated to predominate in the L10 tumor. In a separate set of experiments, L10 and line 1 tumors were established in contralateral thighs in the same animals. L10 tumors were visualized clearly, and tissue uptake of radiolabel was demonstrated to reside predominantly in the L10 tumor.

  12. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

    PubMed Central

    Maina, Theodosia; Konijnenberg, Mark W.; KolencPeitl, Petra; Garnuszek, Piotr; Nock, Berthold A.; Kaloudi, Aikaterini; Kroselj, Marko; Zaletel, Katja; Maecke, Helmut; Mansi, Rosalba; Erba, Paola; von Guggenberg, Elisabeth; Hubalewska-Dydejczyk, Alicja; Mikolajczak, Renata; Decristoforo, Clemens

    2016-01-01

    Introduction From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing double A431-CCK2R(±) xenografts at 1, 4 and 24 h pi. Further 4-h animal groups were either additionally treated with the plasma expander gelofusine or injected with 111In-CP04 prepared by wet-labelling. Pharmacokinetics in healthy mice included the 30 min, 1, 4, 24, 48 and 72 h time points pi. Dosimetric calculations were based on extrapolation of mice data to humans adopting two scaling models. Results CP04 was well-tolerated by both mice and rats, with an LD50 > 178.5 μg/kg body weight for mice and a NOAEL (no-observed-adverse-effect-level) of 89 μg/kg body weight for rats. After labelling, 111In-CP04 remained >70% intact in peripheral mouse blood at 5 min pi. The uptake of 111In-CP04 prepared from the freeze-dried kit and by wet-labelling were comparable in the A431-CCK2R(+)-xenografts (9.24 ± 1.35%ID/g and 8.49 ± 0.39%ID/g, respectively; P > 0.05). Gelofusine-treated mice exhibited significantly reduced kidneys values (1.69 ± 0.15%ID/g vs. 5.55 ± 0.94%ID/g in controls, P < 0.001). Dosimetry data revealed very comparable effective tumour doses for the two scaling models applied, of 0.045 and 0.044 m

  13. Radioimmunotherapy of Solid Tumors: Searching for the Right Target

    PubMed Central

    Song, Hong; Sgouros, George

    2015-01-01

    Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkin’s lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under pre-clinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor. PMID:21034423

  14. Radioimmunotherapy: A Specific Treatment Protocol for Cancer by Cytotoxic Radioisotopes Conjugated to Antibodies

    PubMed Central

    Kawashima, Hidekazu

    2014-01-01

    Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by 90Y-ibritumomab tiuxetan (Zevalin) and 131I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment. PMID:25379535

  15. Radioimmunotherapy of non-Hodgkin's lymphoma: clinical development of the Zevalin regimen.

    PubMed

    Theuer, Charles P; Leigh, Bryan R; Multani, Pratik S; Allen, Roberta S; Liang, Bertrand C

    2004-01-01

    Zevalin (ibritumomab tiuxetan; IDEC Pharmaceuticals Corporation, San Diego, CA, USA) was approved by the United States Food and Drug Administration on February 19, 2002, following 9 years of clinical development. Six clinical studies supported the Zevalin Biologics License Application. The Zevalin regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), and for those with follicular NHL refractory to Rituxan (rituximab, MabThera; IDEC Pharmaceuticals Corporation, San Diego, CA and Genentech, South San Francisco, CA). In the year following FDA approval, approximately 1300 patients were treated in clinical trials or with the commercially available product. PMID:15504711

  16. H2CHXdedpa and H4CHXoctapa-chiral acyclic chelating ligands for (67/68)Ga and (111)In radiopharmaceuticals.

    PubMed

    Ramogida, Caterina F; Cawthray, Jacqueline F; Boros, Eszter; Ferreira, Cara L; Patrick, Brian O; Adam, Michael J; Orvig, Chris

    2015-02-16

    The chiral acyclic ligands H2CHXdedpa (N4O2), H2CHXdedpa-bb (N4O2), and H4CHXoctapa (N4O4) (CHX = cyclohexyl/cyclohexane, H2dedpa = 1,2-[[6-carboxy-pyridin-2-yl]-methylamino]ethane, bb = N,N'-dibenzylated, H4octapa = N,N'-bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N'-diacetic acid) were synthesized, complexed with Ga(III) and/or In(III), and evaluated for their potential as chelating agents in radiopharmaceutical applications. The ligands were compared to the previously studied hexadentate H2dedpa and octadentate H4octapa ligands to determine the effect adding a chiral 1R,2R-trans-cyclohexane to replace the ethylenediamine backbone would have on metal complex stability and radiolabeling kinetics. It was found that [Ga(CHXdedpa)](+) showed very similar properties to those of [Ga(dedpa)](+), with only one isomer in solution observed by NMR spectroscopy, and minimal structural changes in the solid-state X-ray structure. Like [Ga(dedpa)](+), [Ga(CHXdedpa)](+) exhibited exceptionally high thermodynamic stability constants (log KML = 28.11(8)), and the chelate retained the ability to label (67)Ga quantitatively in 10 min at room temperature at ligand concentrations of 1 × 10(-5) M. In vitro kinetic inertness assays demonstrated the [(67)Ga(CHXdedpa)](+) complex to be more stable than [(67)Ga(dedpa)](+) in a human serum competition, with 90.5% and 77.8% of (67)Ga remaining chelate-bound after 2 h, respectively. Preliminary coordination studies of H4CHXoctapa with In(III) demonstrated [In(CHXoctapa)](-) to have an equivalently high thermodynamically stable constant as [In(octapa)](-), with log KML values of 27.16(9) and 26.76(14), respectively. The [(111)In(CHXoctapa)](-) complex showed exceptionally high in vitro kinetic inertness over 120 h in human serum, comparing well with previously reported [(111)In(octapa)](-) values, and an improved stability compared to the current industry "gold standards" 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA

  17. Role for a Zinc Finger Protein (Zfp111) in Transformation of 208F Rat Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Protein

    PubMed Central

    Hsu, Tom; Phung, An; Choe, Kevin; Kim, Jung Woo

    2015-01-01

    ABSTRACT The native envelope gene (env) of Jaagsiekte sheep retrovirus (JSRV) also acts as an oncogene. To investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with Env. Among several candidates, we identified mouse or rat zinc finger protein 111 (zfp111). The interaction between Env and Zfp111 was confirmed through in vivo coimmunoprecipitation assays. Knockdown of endogenous Zfp111 caused a decrease in cell transformation by JSRV Env, while overexpression of Zfp111 increased overall Env transformation, supporting a role for Zfp111 in Env transformation. Knockdown of Zfp111 had no effect on the growth rate of parental rat 208F cells, while it decreased the proliferation rate of JSRV-transformed 208F cells, suggesting that JSRV-transformed cells became dependent on Zfp111. In addition, Zfp111 preferentially bound to a higher-mobility form of JSRV Env that has not been described previously. The higher-mobility form of Env (P70env) was found exclusively in the nuclear fraction, and size of its polypeptide backbone was the same as that of the cytoplasmic Env polyprotein (Pr80env). The differences in glycosylation between the two versions of Env were characterized. These results identify a novel cellular protein, Zfp111, that binds to the JSRV Env protein, and this binding plays a role in Env transformation. These results indicate that JSRV transformation also involves proteins and interactions in the nucleus. IMPORTANCE The envelope protein (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncogene, but its mechanism of cell transformation is still unclear. Here we identified seven candidate cellular proteins that can interact with JSRV Env by yeast two-hybrid screening. This study focused on one of the seven candidates, zinc finger protein 111 (Zfp111). Zfp111 was shown to interact with JSRV Env in cells and to be involved in JSRV transformation. Moreover, coexpression of JSRV Env and Zfp111 led to the

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  19. Radiometals as payloads for radioimmunotherapy for lymphoma.

    PubMed

    DeNardo, Gerald L; Kennel, Stephen J; Siegel, Jeffry A; Denardo, Sally J

    2004-10-01

    Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti-CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and therapy, have been approved for use in patients with non-Hodgkin's lymphoma (NHL). Successful RIT for lymphomas is due in large part to the rapid and efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more difficult to access, necessitating novel strategies matched with radionuclides with specific physical properties. Because there are many radionuclides from which to choose, a systematic approach is required to select those preferred for a specific application. Thus far, radionuclides with g emissions for imaging and particulate emissions for therapy have been investigated. Radionuclides of iodine were the first to be used for RIT. Many conventionally radioiodinated MAbs are degraded after endocytosis by target cells, releasing radioiodinated peptides and amino acids. In contrast, radiometals have been shown to have residualizing properties, advantageous when the MAb is localized in malignant tissue. b-emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive combinations of biologic, physical, radiochemical, production, economic, and radiation safety characteristics. Other radiometals, such as copper-67 and copper-64, are also of interest. a-emitters, including actinium-225 and bismuth-213, have been used for therapy in selected applications. Evidence for the impact of the radionuclide is provided by data from the randomized pivotal phase III trial of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about 2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It is clear that RIT has emerged as a safe and efficient method for treatment of NHL, especially in specific settings. PMID:15498149

  20. The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.

    PubMed

    Gudasheva, T A; Boyko, S S; Ostrovskaya, R U; Voronina, T A; Akparov, V K; Trofimov, S S; Rozantsev, G G; Skoldinov, A P; Zherdev, V P; Seredenin, S B

    1997-01-01

    The metabolism of a new piracetam analogue, the dipeptide cognitive enhancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studied in vivo. GVS-111 itself was not found in rat brain 1 h after 5 mg/kg i.p. administration up to limit of detection (LOD) under high performance liquid chromatography (HPLC) conditions. Three substances corresponding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimental rat brain samples as well as in controls using HPLC, gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Only cyclo-prolylglycine concentration increased (2.5-fold) 1 h after GVS-111 administration. Cyclo-prolylglycine formation from GVS-111 in the presence of plasma and brain enzymes was shown in vitro. These data could be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endogenous cyclopeptide that produces the nootropic activity. PMID:9358206

  1. [Diagnostic utility of 111In-antimyosin Fab scintigraphy in acute myocardial infarction: comparison with 201Tl and 99mTc-pyrophosphate myocardial scintigraphy].

    PubMed

    Morita, M; Naruse, H; Yamamoto, J; Itano, M; Kawamoto, H; Fukutake, N; Ohyanagi, M; Iwasaki, T; Fukuchi, M

    1991-12-01

    To assess the diagnostic accuracy, extent, and characteristics of 111In-antimyosin Fab scintigraphy (In-AM) in acute myocardial infarction (AMI), we studied In-AM in 17 patients with AMI and compared with In-AM, 99mTc-PYP and 201Tl scintigraphy. Intensity of In-AM uptake was classified into 3 grades. Fourteen of 17 patients (82%) showed positive uptake of In-AM. The locations of infarct area diagnosed by In-AM were in accordance with those by electrocardiography. There was a good correlation between the extent score of In-AM planar and that of SPECT (r = 0.72), In-AM SPECT and Tl SPECT (r = 0.79), In-AM planar and PYP planar (r = 0.92), In-AM SPECT and PYP SPECT (r = 0.76), respectively (p less than 0.01). Thus, In-AM is a useful method for diagnosis of AMI. PMID:1838398

  2. Functional Characterization of Novel Chitinase Genes Present in the Sheath Blight Resistance QTL: qSBR11-1 in Rice Line Tetep.

    PubMed

    Richa, Kamboj; Tiwari, Ila M; Kumari, Mandeep; Devanna, B N; Sonah, Humira; Kumari, Archana; Nagar, Ramawatar; Sharma, Vinay; Botella, Jose R; Sharma, Tilak R

    2016-01-01

    Rice sheath blight disease caused by Rhizoctonia solani is one of the most devastating diseases in rice leading to heavy yield losses. Due to the polygenic nature of resistance, no major resistance gene with complete host resistance against R. solani has been reported. In this study, we have performed molecular and functional analysis of the genes associated with the major R. solani-resistance QTL qSBR11-1 in the indica rice line Tetep. Sequence analysis revealed the presence of a set of 11 tandem repeats containing genes with a high degree of homology to class III chitinase defense response genes. Real-time quantitative PCR analysis showed that all the genes are strongly induced 36 h after R. solani infection. Comparison between the resistant Tetep and the susceptible HP2216 lines shows that the induction of the chitinase genes is much higher in the Tetep line. Recombinant protein produced in vitro for six of the eleven genes showed chitinolytic activity in gel assays but we did not detect any xylanase inhibitory activity. All the six in vitro expressed proteins show antifungal activity with a clear inhibitory effect on the growth of the R. solani mycelium. The characterized chitinase genes can provide an important resource for the genetic improvement of R. solani susceptible rice lines for sheath blight resistance breeding. PMID:26973685

  3. Use of galactosylated-streptavidin as a clearing agent with 111In-labeled, biotinylated antibodies to enhance tumor/non-tumor localization ratios.

    PubMed

    Govindan, Serengulam V; Griffiths, Gary L; Michel, Rosana B; Andrews, Philip M; Goldenberg, David M; Mattes, M Jules

    2002-06-01

    Optimal tumor imaging using radiolabeled antibodies (Abs) depends on obtaining the highest possible tumor/non-tumor localization ratios. To increase this ratio, in a mouse xenograft model system, we induced rapid blood clearance of the Ab after extensive penetration of a solid tumor, at 24 hr after Ab injection. By using galactosylated streptavidin (gal-SA) as a clearing agent for biotinylated Abs, and by using an 111In-DTPA (diethylenetriaminepentaacetic acid) label, clearance was directed to hepatocytes (as opposed to Kupffer cells), and the radiolabel was excreted by the hepatocytes into bile, thereby reducing accumulation in the liver. In this study, we directly compared this approach with the use of 99mTc-F(ab)2 fragments, using the same Ab to carcinoembryonic antigen (CEA), with a colon carcinoma xenograft. The gal-SA clearance method produced substantially higher tumor/non-tumor localization ratios for all tissues except the liver, and even for the liver the disadvantage of the gal-SA clearance method was small. We also tested the gal-SA clearance method with a xenograft model of human B-cell lymphoma, using anti-CD22. High tumor/non-tumor ratios were obtained, as previously described with carcinomas of the lung and colon. Therefore, this approach appears to be a generally applicable strategy to obtain relatively high tumor/non-tumor ratios. PMID:12136523

  4. Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer

    PubMed Central

    2012-01-01

    Background Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes. Methods Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5. Results The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5. Conclusions This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging. PMID:22541756

  5. Functional Characterization of Novel Chitinase Genes Present in the Sheath Blight Resistance QTL: qSBR11-1 in Rice Line Tetep

    PubMed Central

    Richa, Kamboj; Tiwari, Ila M.; Kumari, Mandeep; Devanna, B. N.; Sonah, Humira; Kumari, Archana; Nagar, Ramawatar; Sharma, Vinay; Botella, Jose R.; Sharma, Tilak R.

    2016-01-01

    Rice sheath blight disease caused by Rhizoctonia solani is one of the most devastating diseases in rice leading to heavy yield losses. Due to the polygenic nature of resistance, no major resistance gene with complete host resistance against R. solani has been reported. In this study, we have performed molecular and functional analysis of the genes associated with the major R. solani-resistance QTL qSBR11-1 in the indica rice line Tetep. Sequence analysis revealed the presence of a set of 11 tandem repeats containing genes with a high degree of homology to class III chitinase defense response genes. Real-time quantitative PCR analysis showed that all the genes are strongly induced 36 h after R. solani infection. Comparison between the resistant Tetep and the susceptible HP2216 lines shows that the induction of the chitinase genes is much higher in the Tetep line. Recombinant protein produced in vitro for six of the eleven genes showed chitinolytic activity in gel assays but we did not detect any xylanase inhibitory activity. All the six in vitro expressed proteins show antifungal activity with a clear inhibitory effect on the growth of the R. solani mycelium. The characterized chitinase genes can provide an important resource for the genetic improvement of R. solani susceptible rice lines for sheath blight resistance breeding. PMID:26973685

  6. Phase I trial to evaluate the tumor and normal tissue uptake, radiation dosimetry and safety of 111In-DTPA-human epidermal growth factor in patients with metastatic EGFR-positive breast cancer

    PubMed Central

    Vallis, Katherine A; Reilly, Raymond M; Scollard, Deborah; Merante, Pat; Brade, Anthony; Velauthapillai, Sobi; Caldwell, Curtis; Chan, Ida; Freeman, Marc; Lockwood, Gina; Miller, Naomi A; Cornelissen, Bart; Petronis, Jennifer; Sabate, Kathryn

    2014-01-01

    The safety, pharmacokinetics, biodistribution and radiation dosimetry of 111In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. 111In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received 111In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. 111In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and β-phase T½ of 9.41 ± 1.93 h. 111In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of 111In-DTPA-hEGF were well

  7. AFTI F-111 in flight

    NASA Technical Reports Server (NTRS)

    1986-01-01

    This NASA Ames-Dryden Flight Research Facility photograph shows a modified General Dynamics AFTI/F-111A Aardvark with supercritical mission adaptive wings (MAW) installed. The Aircraft is in a banking turn towards Rogers Dry Lake and Edwards Air Force Base, California. With the phasing out of the TACT program came a renewed effort by the Air Force Flight Dynamics Laboratory to extend supercritical wing technology to a higher level of performance. In the early 1980s the supercritical wing on the F-111A aircraft was replaced with a wing built by Boeing Aircraft Company System called a 'mission adaptive wing' (MAW), and a joint NASA and Air Force program called Advanced Fighter Technology Integration (AFTI) was born.

  8. AFTI F-111 in flight

    NASA Technical Reports Server (NTRS)

    1986-01-01

    This NASA Ames-Dryden Flight Research Facility photograph shows a modified General Dynamics AFTI/F-111A Aardvark with supercritical mission adaptive wings (MAW) installed. In this photograph the AFTI/F111A is seen banking towards Rodgers Dry Lake and Edwards Air Force Base. With the phasing out of the TACT program came a renewed effort by the Air Force Flight Dynamics Laboratory to extend supercritical wing technology to a higher level of performance. In the early 1980s the supercritical wing on the F-111A aircraft was replaced with a wing built by Boeing Aircraft Company System called a 'mission adaptive wing' (MAW), and a joint NASA and Air Force program called Advanced Fighter Technology Integration (AFTI) was born.

  9. Dynamic hyperfine interactions in 111In(111Cd)-doped ZnO semiconductor: PAC results supported by ab initio calculations

    NASA Astrophysics Data System (ADS)

    Muñoz, Emiliano L.; Mercurio, Marcio E.; Cordeiro, Moacir R.; Pereira, Luciano F. D.; Carbonari, Artur W.; Rentería, Mario

    2012-08-01

    In this work, we present results of Time-Differential γ-γ Perturbed-Angular-Correlations (PAC) experiments performed in 111Cd-doped ZnO semiconductor. The PAC technique has been applied in order to characterize the electric-field-gradient (EFG) tensor at (111In (EC)→) 111Cd nuclei located, as was later demonstrated, at defect-free cation sites of the ZnO host structure. The PAC experiments were performed in the temperature range of 77-1075 K. At first glance, the unexpected presence of low-intensity dynamic hyperfine interactions was observed, which were analyzed with a perturbation factor based on the Bäverstam and Othaz model. The experimental EFG results were compared with ab initio calculations performed with the Full-Potential Augmented Plane Wave plus local orbital (FP-APW+lo) method, in the framework of the Density Functional Theory (DFT), using the Wien2K code. The presence of the dynamic hyperfine interactions has been analyzed enlightened by the FP-APW+lo calculations of the EFG performed as a function of the charge state of the cell. We could correlate the large strength of the dynamic hyperfine interaction with the strong variation of the EFG due to changes in the electronic charge distribution in the Cd vicinity during the time-window of the PAC measurement. It was also revealed that the Cd impurity decays to a final stable neutral charge state (Cd2+) fast enough (in few ns) to produce the nearly undamped observed PAC spectra.

  10. /sup 111/In-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

    SciTech Connect

    Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

    1982-09-01

    The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of /sup 111/In-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT.

  11. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model

    PubMed Central

    Nielsen, Ole L; Afzelius, Pia; Bender, Dirk; Schønheyder, Henrik C; Leifsson, Páll S; Nielsen, Karin M; Larsen, Jytte O; Jensen, Svend B; Alstrup, Aage KO

    2015-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195 and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195 accumulated in only one lesion. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. 11C-methionine and possibly 68Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  12. Comparison of autologous (111)In-leukocytes, (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model.

    PubMed

    Nielsen, Ole L; Afzelius, Pia; Bender, Dirk; Schønheyder, Henrik C; Leifsson, Páll S; Nielsen, Karin M; Larsen, Jytte O; Jensen, Svend B; Alstrup, Aage Ko

    2015-01-01

    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, (18)F-FDG accumulated in nine, (111)In-leukocytes in eight, (11)C-methionine in six, (68)Ga-citrate in four and (11)C-PK11195 accumulated in only one lesion. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. (11)C-methionine and possibly (68)Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  13. Survival of density subpopulations of rabbit platelets: use of /sup 51/Cr-or /sup 111/In-labeled platelets to measure survival of least dense and most dense platelets concurrently

    SciTech Connect

    Rand, M.L.; Packham, M.A.; Mustard, J.F.

    1983-02-01

    The origin of the density heterogeneity of platelets was studied by measuring the survival of density subpopulations of rabbit platelets separated by discontinuous Stractan density gradient centrifugation. When a total population of /sup 51/Cr-labelled platelets was injected into recipient rabbits, the relative specific radioactivity of the most dense platelets decreased rapidly. In contrast, that of the least dense platelets had not changed 24 hr after injection, and then decreased slowly. To distinguish between the possibilities that most dense platelets are cleared from the circulation more quickly than least dense platelets or that platelets decrease in density as they age in the circulation, the concurrent survival of least dense and most dense platelets, labelled with either /sup 51/Cr or /sup 111/In-labelled total platelet populations, determined concurrently in the same rabbits, are identical, calculated from 1 hr values as 100%. However, the 1-hr recovery of /sup 111/In-labelled platelets was slightly but significantly less than that of /sup 51/Cr-labelled platelets. Therefore, researchers studied the survival of /sup 51/Cr-labelled least dense and /sup 111/In-labelled most dense platelets as well as that of /sup 111/In-labelled least dense and /sup 51/Cr-labelled most dense platelets. Mean 1-hr recovery of least dense platelets, labelled with either isotope (78% +/- 7%, SD) was similar to that of most dense platelets, labelled with either isotope (77% +/- 8%; SD). Mean survival of least dense platelets was 47.3 +/- 18.7 hr (SD), which was significantly less than that of most dense platelets (76.1 +/- 21.6 hr; SD) (p less than 0.0025). These results indicate that platelets decrease in buoyant density as they age in the circulation and that most dense platelets are enriched in young platelets, and least dense in old.

  14. Position for site-specific attachment of a DOTA chelator to synthetic affibody molecules has a different influence on the targeting properties of 68Ga- compared to 111in-labeled conjugates.

    PubMed

    Honarvar, Hadis; Strand, Joanna; Perols, Anna; Orlova, Anna; Selvaraju, Ram Kumar; Eriksson Karlström, Amelie; Tolmachev, Vladimir

    2014-01-01

    Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the C-terminus. The biodistribution of 68Ga- and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers, and the influence was more pronounced for 68Ga-labeled Affibody molecules than for the 111In-labeled counterparts. The best 68Ga-labeled variant was 68Ga-[DOTA-A1]-ZHER2:S1, which provided a tumor uptake of 13 ± 1 %ID/g and a tumor to blood ratio of 39 ± 12 at 2 hours after injection. 111In-[DOTA-A1]-ZHER2:S1 and 111In-[DOTA-K58]-ZHER2:S1 were equally good at this time point, providing a tumor uptake of 15 to 16 %ID/g and a tumor to blood ratio in the range of 60 to 80. In conclusion, the selection of the best position for a chelator in Affibody molecules can be used for optimization of their imaging properties. This may be important for the development of Affibody-based and other protein-based imaging probes. PMID:25249017

  15. Evaluation of quantitative imaging methods for organ activity and residence time estimation using a population of phantoms having realistic variations in anatomy and uptake

    PubMed Central

    He, Bin; Du, Yong; Segars, W. Paul; Wahl, Richard L.; Sgouros, George; Jacene, Heather; Frey, Eric C.

    2009-01-01

    Estimating organ residence times is an essential part of patient-specific dosimetry for radioimmunotherapy (RIT). Quantitative imaging methods for RIT are often evaluated using a single physical or simulated phantom but are intended to be applied clinically where there is variability in patient anatomy, biodistribution, and biokinetics. To provide a more relevant evaluation, the authors have thus developed a population of phantoms with realistic variations in these factors and applied it to the evaluation of quantitative imaging methods both to find the best method and to demonstrate the effects of these variations. Using whole body scans and SPECT∕CT images, organ shapes and time-activity curves of 111In ibritumomab tiuxetan were measured in dosimetrically important organs in seven patients undergoing a high dose therapy regimen. Based on these measurements, we created a 3D NURBS-based cardiac-torso (NCAT)-based phantom population. SPECT and planar data at realistic count levels were then simulated using previously validated Monte Carlo simulation tools. The projections from the population were used to evaluate the accuracy and variation in accuracy of residence time estimation methods that used a time series of SPECT and planar scans. Quantitative SPECT (QSPECT) reconstruction methods were used that compensated for attenuation, scatter, and the collimator-detector response. Planar images were processed with a conventional (CPlanar) method that used geometric mean attenuation and triple-energy window scatter compensation and a quantitative planar (QPlanar) processing method that used model-based compensation for image degrading effects. Residence times were estimated from activity estimates made at each of five time points. The authors also evaluated hybrid methods that used CPlanar or QPlanar time-activity curves rescaled to the activity estimated from a single QSPECT image. The methods were evaluated in terms of mean relative error and standard deviation of

  16. Evaluation of quantitative imaging methods for organ activity and residence time estimation using a population of phantoms having realistic variations in anatomy and uptake

    SciTech Connect

    He Bin; Du Yong; Segars, W. Paul; Wahl, Richard L.; Sgouros, George; Jacene, Heather; Frey, Eric C.

    2009-02-15

    Estimating organ residence times is an essential part of patient-specific dosimetry for radioimmunotherapy (RIT). Quantitative imaging methods for RIT are often evaluated using a single physical or simulated phantom but are intended to be applied clinically where there is variability in patient anatomy, biodistribution, and biokinetics. To provide a more relevant evaluation, the authors have thus developed a population of phantoms with realistic variations in these factors and applied it to the evaluation of quantitative imaging methods both to find the best method and to demonstrate the effects of these variations. Using whole body scans and SPECT/CT images, organ shapes and time-activity curves of 111In ibritumomab tiuxetan were measured in dosimetrically important organs in seven patients undergoing a high dose therapy regimen. Based on these measurements, we created a 3D NURBS-based cardiac-torso (NCAT)-based phantom population. SPECT and planar data at realistic count levels were then simulated using previously validated Monte Carlo simulation tools. The projections from the population were used to evaluate the accuracy and variation in accuracy of residence time estimation methods that used a time series of SPECT and planar scans. Quantitative SPECT (QSPECT) reconstruction methods were used that compensated for attenuation, scatter, and the collimator-detector response. Planar images were processed with a conventional (CPlanar) method that used geometric mean attenuation and triple-energy window scatter compensation and a quantitative planar (QPlanar) processing method that used model-based compensation for image degrading effects. Residence times were estimated from activity estimates made at each of five time points. The authors also evaluated hybrid methods that used CPlanar or QPlanar time-activity curves rescaled to the activity estimated from a single QSPECT image. The methods were evaluated in terms of mean relative error and standard deviation of the

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-06-01

    , fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride

  18. Evaluation of quantitative imaging methods for organ activity and residence time estimation using a population of phantoms having realistic variations in anatomy and uptake.

    PubMed

    He, Bin; Du, Yong; Segars, W Paul; Wahl, Richard L; Sgouros, George; Jacene, Heather; Frey, Eric C

    2009-02-01

    Estimating organ residence times is an essential part of patient-specific dosimetry for radioimmunotherapy (RIT). Quantitative imaging methods for RIT are often evaluated using a single physical or simulated phantom but are intended to be applied clinically where there is variability in patient anatomy, biodistribution, and biokinetics. To provide a more relevant evaluation, the authors have thus developed a population of phantoms with realistic variations in these factors and applied it to the evaluation of quantitative imaging methods both to find the best method and to demonstrate the effects of these variations. Using whole body scans and SPECT/CT images, organ shapes and time-activity curves of 111In ibritumomab tiuxetan were measured in dosimetrically important organs in seven patients undergoing a high dose therapy regimen. Based on these measurements, we created a 3D NURBS-based cardiac-torso (NCAT)-based phantom population. SPECT and planar data at realistic count levels were then simulated using previously validated Monte Carlo simulation tools. The projections from the population were used to evaluate the accuracy and variation in accuracy of residence time estimation methods that used a time series of SPECT and planar scans, Quantitative SPECT (QSPECT) reconstruction methods were used that compensated for attenuation, scatter, and the collimator-detector response. Planar images were processed with a conventional (CPlanar) method that used geometric mean attenuation and triple-energy window scatter compensation and a quantitative planar (QPlanar) processing method that used model-based compensation for image degrading effects. Residence times were estimated from activity estimates made at each of five time points. The authors also evaluated hybrid methods that used CPlanar or QPlanar time-activity curves rescaled to the activity estimated from a single QSPECT image. The methods were evaluated in terms of mean relative error and standard deviation of the

  19. The Impact of 3D Volume-of-Interest Definition on Accuracy and Precision of Activity Estimation in Quantitative SPECT and Planar Processing Methods

    PubMed Central

    He, Bin; Frey, Eric C.

    2010-01-01

    Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise, and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT), and planar (QPlanar) processing. Another important effect impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimations. The 3D NCAT phantom was used with activities that modeled clinically observed 111In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in the same transaxial plane in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g., in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from −1 to 1 voxels in increments of 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ

  20. In Vivo Biodistribution, PET Imaging, and Tumor Accumulation of 86Y- and 111In-Antimindin/RG-1, Engineered Antibody Fragments in LNCaP Tumor–Bearing Nude Mice

    PubMed Central

    Schneider, Douglas W.; Heitner, Tara; Alicke, Bruno; Light, David R.; McLean, Kirk; Satozawa, Noboru; Parry, Gordon; Yoo, Jeongsoo; Lewis, Jason S.; Parry, Renate

    2016-01-01

    To optimize in vivo tissue uptake kinetics and clearance of engineered monoclonal antibody (mAb) fragments for radiotherapeutic and radiodiagnostic applications, we compared the biodistribution and tumor localization of four 111In- and 86Y-labeled antibody formats, derived from a single antimindin/RG-1 mAb, in a prostate tumor model. The IgG, diabody, single-chain variable domain (scFv), and novel miniantibody formats, composed of the human IgE-CH4 and a modified IgG1 hinge linked to scFv domains, were compared. Methods Antibodies were first derivatized with the bifunctional chelator CHX-A″-diethylenetriamine pentaacetic acid and then bound to the radiometal to create radiolabeled immunoconjugates. Human LNCaP xenografts were grown in nude mice, and 111In- or 86Y-labeled antibodies were administered intravenously. Tissues were harvested at different times, and the level of antibody deposition was determined by measuring radioactivity. Whole-body small-animal PET of mice receiving 86Y-labeled antibodies was performed at 6 time points and colocalized with simultaneous micro-CT imaging. Results The biodistributions of 111In and 86Y antibodies were quite similar. The blood, tumor, kidney, and liver tissues contained varying levels of radioactivity. The antibody accumulation in the tumor correlated with molecular size. The IgG steadily increased with time to 24.1 percentage injected dose per gram (%ID/g) at 48 h. The miniantibody accumulated at a similar rate to reach a lower level (14.2 %ID/g) at 48 h but with a higher tumor-to-blood ratio than the IgG. Tumor accumulation of the diabody peaked at 3 h, reaching a much lower level (3.7 %ID/g). A combination of rapid clearance and lower relative affinity of the scFv precluded deposition in the tumor. Small-animal PET results correlated well with the biodistribution results, with similar tumor localization patterns. Conclusion The larger antibody formats (IgG and miniantibody) gave higher tumor uptake levels than did the

  1. Imaging agents for in vivo molecular profiling of disseminated prostate cancer--targeting EGFR receptors in prostate cancer: comparison of cellular processing of [111In]-labeled affibody molecule Z(EGFR:2377) and cetuximab.

    PubMed

    Malmberg, Jennie; Tolmachev, Vladimir; Orlova, Anna

    2011-04-01

    Expression of receptor tyrosine-kinase (RTK) EGFR is low in normal prostate, but increases in prostate cancer. This receptor is significantly up-regulated as tumors progress into higher grade, androgen-insensitive and metastatic lesions. The up-regulated receptors could serve as targets for novel selective anti-cancer drugs, e.g. antibodies and tyrosine kinase inhibitors. Radionuclide imaging of RTK can facilitate patient stratification and monitoring of anti-RTK therapy of prostate cancer. The goal of the study was to evaluate binding and cellar processing of radiolabeled EGFR-targeting conjugates by prostate cancer cell lines. Receptor expression of EGFR was studied in three prostate cancer cell lines: DU145 (brain metastasis of PC, hormone insensitive), PC3 (bone metastasis of PC) and LNCaP (lymph node metastasis of PC, androgen and estrogen receptor positive). Uptake and internalization of anti-EGFR mAbs (cetuximab) and affibody molecule (Z2377) labeled with indium-111 was investigated. EGFR expression on prostate cancer cell lines was clearly demonstrated. Both labelled conjugates 111In-Z2377 and 111In-cetuximab bound to prostate cancer cells in the receptor mediated model. Expression levels were modest but correlate with degree of hormone independence. Internalization of Affibody molecules was relatively slow in all cell lines. Internalization of mAbs was more rapid. The level of EGFR expression in these cell lines is sufficient for in vivo molecular imaging. Slow internalization indicates possibility of the use of non-residualizing labels for affibody molecules. PMID:21253675

  2. A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In-labelled radiopharmaceuticals.

    PubMed

    Amato, Ernesto; Leotta, Salvatore; Italiano, Antonio; Baldari, Sergio

    2015-07-01

    The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations. PMID:25979209

  3. Long-term follow-up of {sup 111}In-capromab pendetide (ProstaScint) scan as pretreatment assessment in patients who undergo salvage radiotherapy for rising prostate-specific antigen after radical prostatectomy for prostate cancer

    SciTech Connect

    Nagda, Suneel N. . E-mail: snagda@gmail.com; Mohideen, Najeeb; Lo, Simon S.; Khan, Usman B.S.; Dillehay, Gary; Wagner, Robert; Campbell, Steven; Flanigan, Robert

    2007-03-01

    Purpose: To evaluate the long-term failure patterns in patients who underwent an {sup 111}In-capromab pendetide (ProstaScint) scan as part of their pretreatment assessment for a rising prostate-specific antigen (PSA) level after prostatectomy and subsequently received local radiotherapy (RT) to the prostate bed. Methods: Fifty-eight patients were referred for evaluation of a rising PSA level after radical prostatectomy. All patients had negative findings for metastatic disease after abdominal/pelvis imaging with CT and isotope bone scans. All patients underwent a capromab pendetide scan, and the sites of uptake were noted. All patients were treated with local prostate bed RT (median dose 66.6 Gy). Results: Of the 58 patients, 20 had biochemical failure (post-RT PSA level >0.2 ng/mL or a rise to greater than the nadir PSA), including 6 patients with positive uptake outside the bed (positive elsewhere). The 4-year biochemical relapse-free survival (bRFS) rates for patients with negative (53%), positive in the prostate bed alone (45%), or positive elsewhere (74%) scan findings did not differ significantly (p = 0.51). The positive predictive value of the capromab pendetide scan in detecting disease outside the bed was 27%. The capromab pendetide scan status had no effect on bRFS. Those with a pre-RT PSA level of <1 ng/mL had improved bRFS (p = 0.003). Conclusion: The capromab pendetide scan has a low positive predictive value in patients with positive elsewhere uptake and the 4-year bRFS was similar to that for those who did not exhibit positive elsewhere uptake. Therefore, patients with a postprostatectomy rising PSA level should considered for local RT on the basis of clinicopathologic factors.

  4. Radioimmunotherapy for Waldenstrom's macroglobulinemia.

    PubMed

    Emmanouilides, Christos

    2003-04-01

    Radioimmunotherapy targeting CD20 is a promising novel treatment for lymphoma. Prior trials have established the safe dose of Zevalin ((90)Y-ibritumomab tiuxetan; IDEC Pharmaceuticals) for patients with no more than 25% bone marrow (BM) involvement. Zevalin is expected to be an effective treatment for WM; however, the safe dose has not been defined. A phase I clinical trial has been designed to define the maximum-tolerated dose (MTD) of Zevalin in patients with WM and BM involvement up to 50%. Eligible patients need to have adequate hematologic indices (absolute neutrophil count [ANC] > 1,500/microL, platelets > 100,000/microL). The starting dose of (90)Y-Zevalin is 0.08 mCi/kg. Dose escalation by 0.04 mCi/kg in cohorts of three to six patients will be performed. Patients will be re-treated at 12 weeks if there is no complete response, no progression, and no dose-limiting toxicity. If the degree of BM involvement remains in the 20% to 50% range, re-treatment will involve a similar dose of Zevalin; if it is <20%, patients will receive Zevalin to the maximum allowed cumulative dose of 0.4 mCi/kg (or 0.3 mCi/kg for mild thrombocytopenia). Despite the phase I design, the re-treatment provision is expected to result in significant clinical benefit. PMID:12720148

  5. Radioimmunotherapy in relapsed follicular lymphoma previously treated by autologous bone marrow transplant: a report of eight new cases and literature review.

    PubMed

    Peyrade, Frederic; Triby, Caroline; Slama, Bohane; Fontana, Xavier; Gressin, Remy; Broglia, Jean-Marc; Lepeu, Gerard; Carrier, Patricia; Peyrottes, Isabelle; Darcourt, Jacques; Bondiau, Pierre-Yves; Thyss, Antoine

    2008-09-01

    Multicenter, retrospective study of standard-dose RIT in eight heavily pre-treated patients with CD20-positive follicular lymphoma who had relapsed after previous autologous bone marrow transplantation (ABMT). Patients underwent nine courses of (90)Y-ibritumomab tiuxetan (0.3 or 0.4 mCi/kg body weight). Responses included five CR, two PR, one SD and one PD. Median DFS was 12 months with median follow-up of 17 months and 1-year OS was 83% (7/8 patients). Grade 4 thrombocytopenia occurred in 7/9 treatments, with no episodes of bleeding, and only two patients received a platelet transfusion. One patient, who had 20% bone marrow involvement at the time of relapse diagnosis, presented with Grade 4 thrombocytopenia and Grade 4 neutropenia and died of septic shock 6 months after RIT. One other case of Grade 4 neutropenia, without a serious infectious syndrome, was observed. Standard-dose RIT seems feasible and potentially effective after ABMT in correctly selected patients with follicular lymphoma. PMID:18661403

  6. Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients.

    PubMed

    Leahy, Michael F; Turner, J Harvey

    2011-01-01

    Radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) has achieved objective response rates in clinical trials comparable with standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but is relatively underused in routine practice. In this article, we report our clinical experience in 142 consecutive patients who received iodine-131 rituximab radioimmunotherapy for low-grade, predominantly follicular, relapsed NHL. Objective response rates of 67%, with complete response (CR) in 50% and median overall survival of 32 months, matched the response rates in a phase 2 clinical trial of (131)I-rituximab radioimmunotherapy and compares favorably with those reported for (131)I-tositumomab or (90)Y-ibritumomab tiuxetan. Progression-free survival was 18 months overall and 32 months in CR or CR-unconfirmed patients. Our patients comprised 107 (75%) follicular lymphoma, 21 (15%) small lymphocytic lymphoma, 6 (4%) mucosa-associated lymphoid tissue/marginal zone lymphoma, and 8 (6%) mantle-cell lymphoma, with median follow-up of 32 months and 8-year overall survival of 48%. Toxicity was limited to hematologic grade 4 neutropenia, occurring in 10% and thrombocytopenia in 6%. There were no episodes of bleeding or infection requiring hospital admission. Radioimmunotherapy with (131)I-rituximab in routine clinical outpatient practice provides cost-effective, safe treatment of relapsed/refractory indolent NHL, with half of patients achieving durable, complete remission with potential for repeat radioimmunotherapy on relapse. PMID:20864582

  7. Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas.

    PubMed

    Cilley, Jeffrey; Winter, Jane N

    2006-01-01

    Relapse continues to be the primary cause of treatment failure in patients with non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have been associated with high response rates, durable remissions and limited toxicity apart from myelosuppression, making them ideal candidates for use in autotransplantation. Tested first as single agents in relapsed patients with indolent and transformed NHL, and then at much higher doses with stem cell support, these agents have now been combined with high-dose chemotherapy prior to autologous stem cell transplant. Radioimmunoconjugates have been used to replace total body irradiation (TBI) in some studies and to augment standard chemotherapy regimens in others. Thus far the results are promising, with combinations of radioimmunoconjugates and chemotherapy producing long-lasting responses in high-risk patients with no more toxicity than that caused by standard conditioning regimens. These results are notable in light of the fact that the dose of radiation delivered to the tumor is 10-fold higher than the dose achievable with TBI. Whether this increase in radiation dose to the targeted lymphoma translates into more durable remissions and an improvement in overall survival requires further investigation. PMID:16434379

  8. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    PubMed

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades. PMID:15640788

  9. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-05-01

    (-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-01-01

    [90Y-DOTA-Tyr3]octreotate, Abatacept, ABT-888, ACE-011, Adefovir dipivoxil, Alosetron hydrochloride, Aminolevulinic acid methyl ester, Amlodipine, Apaziquone, Aripiprazole, AS-101, Atomoxetine hydrochloride, Atrasentan, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Bosentan, Brivanib alaninate; CERE-120, Cetuximab, Ciclesonide, Cinacalcet hydrochloride, Combretastatin A-1 phosphate, Conatumumab, CT-322; Dabigatran etexilate, Darunavir, Deforolimus, Desloratadine, Doripenem, Doxorubicin eluting beads, Duloxetine hydrochloride, Dutasteride; Escitalopram oxalate, Eszopiclone, Etravirine, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fluticasone furoate, Fondaparinux sodium; Gabapentin enacarbil, Ghrelin (human), Golimumab; IC-51, IDM-2, JX-594; Lidocaine/prilocaine, Liraglutide, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Men ACWY, MxdnG1; Naproxcinod; OBP-301, Omalizumab; Paclitaxel nanoparticles, Pasireotide, Pazopanib hydrochloride, Pegaptanib octasodium, Peginterferon alfa-2a, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Prasterone, Pregabalin; Raclopride, Ranelic acid distrontium salt, Ranibizumab, RB-006, Recombinant human relaxin H2, REG1, Regadenoson, Reximmune-C, Rilonacept; Saxagliptin, SCH-697243, Solifenacin succinate, Sorafenib; Tadalafil, Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tipifarnib, Tolvaptan; Vardenafil hydrochloride hydrate, Vicriviroc, Volociximab, Vorinostat; WB-1001; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19798455

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

    disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Ticlopidine hydrochloride, Tigecycline, TST-10088, Tularemia vaccine, Valsartan/amlodipine besylate, Vandetanib, Vardenafil hydrochloride hydrate, Vincristine, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:20094643

  12. Radioimmunoconjugates for the treatment of cancer.

    PubMed

    Kraeber-Bodéré, Françoise; Bodet-Milin, Caroline; Rousseau, Caroline; Eugène, Thomas; Pallardy, Amandine; Frampas, Eric; Carlier, Thomas; Ferrer, Ludovic; Gaschet, Joëlle; Davodeau, François; Gestin, Jean-François; Faivre-Chauvet, Alain; Barbet, Jacques; Chérel, Michel

    2014-10-01

    Radioimmunotherapy (RIT) has been developed for more than 30 years. Two products targeting the CD20 antigen are approved in the treatment of non-Hodgkin B-cell lymphoma (NHBL): iodine 131-tositumomab and yttrium 90-ibritumomab tiuxetan. RIT can be integrated in clinical practice for the treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy. High-dose treatment, RIT in first-line treatment, fractionated RIT, and use of new humanized monoclonal antibodies (MAbs), in particular targeting CD22, showed promising results in NHBL. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiation and less accessible to large molecules such as MAbs, clinical efficacy remains limited. However, pretargeting methods have shown clinical efficacy. Finally, new beta emitters such as lutetium 177, with better physical properties will further improve the safety of RIT and alpha emitters, such as bismuth 213 or astatine 211, offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the consolidation setting. Personalized treatments, based on quantitative positron emission tomography (PET), pre-therapeutic imaging, and dosimetry procedures, also could be applied to adapt injected activity to each patient. PMID:25440606

  13. Radioimmunotherapy of lymphoma: Bexxar and Zevalin.

    PubMed

    Goldsmith, Stanley J

    2010-03-01

    Radioimmunotherapy is a form of targeted radionuclide therapy that uses a monoclonal antibody to deliver localized radiation. It is most appropriate for treatment of multiple tumor sites that cannot be readily excised surgically or irradiated using external beam radiation or brachytherapy. At present, 2 products, Bexxar ((131)I-tositumomab and unlabeled tositumomab, GlaxoSmithKline, Triangle Park, NC) and Zevalin ((90)Y-ibritumomab tiuxetan and unlabeled rituximab, Spectrum Pharmaceuticals, Irvine, CA and Cell Therapeutics, Seattle, WA) are approved for treatment of non-Hodgkin's lymphoma in certain clinical situations in the United States and Canada. Zevalin is available also in Europe, and there are plans to make both agents more widely available. The therapeutic dose to be used depends upon a number of patient-specific variables. Both regimen achieve a complete response or partial response in approximately 3 of 4 patients, with a duration of remission lasting many years in some cases. This article reviews the basis for dose selection, the nuclear medicine procedures involved, the results obtained to date, and issues related to patient and staff safety. PMID:20113680

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    fumarate, Tocilizumab, Tositumomab/iodine (I131) tositumomab, Trabectedin, TransVax™ hepatitis C vaccine; Ustekinumab; V-260, Valspodar, Varenicline tartrate, VCL-IPT1, Vildagliptin, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VRC-HIVDNA016-00-VP; Yttrium 90 (90Y) ibritumomab tiuxetan, Yttrium Y90 Epratuzumab; Zibotentan, Zotarolimus-eluting stent. PMID:21225019

  15. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402.

    PubMed

    Witzig, Thomas E; Hong, Fangxin; Micallef, Ivana N; Gascoyne, Randy D; Dogan, Ahmet; Wagner, Henry; Kahl, Brad S; Advani, Ranjana H; Horning, Sandra J

    2015-09-01

    Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of ≥75% to RCHOP and (90) Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4-6 cycles of RCHOP followed by RIT [14·8 MBq/kg (0·4 mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30 Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty-eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77-96%). With a median follow-up of 5·9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-06-01

    ; Valganciclovir hydrochloride, val-mCyd, vardenafil hydrochloride hydrate, vinflunine, voriconazole; Ximelagatran, XTL-002; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:15319815

  17. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    , sirolimus-eluting stent, solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y) edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin. PMID:16894408

  18. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    , Pseudostat; R24, rasburicase, RHAMM R3 peptide, rilonacept, rosuvastatin calcium, rotavirus vaccine, rufinamide; Sabarubicin hydrochloride, SHL-749, sirolimus-eluting stent, SLx-2101, sodium butyrate, sorafenib, SU-6668; TachoSil, tadalafil, taxus, tegaserod maleate, telbivudine, tenofovir disoproxil fumarate, teriparatide, tetramethylpyrazine, teverelix, tiotropium bromide, tipifarnib, tirapazamine, tolvaptan, TransvaxTM hepatitis C vaccine, treprostinil sodium; Valganciclovir hydrochloride, valsartan/amlodipine, vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, veglin, voriconazole; Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zotarolimus, zotarolimus-eluting stent. PMID:17003851

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    , testosterone gel, tezosentan disodium, tipifarnib, tolvaptan, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Vardenafil hydrochloride hydrate; Xcellerated T cells, XR-5944; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziconotide. PMID:15349141

  1. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    phosphate; Vandetanib, VIA-2291, Vinflunine, Vorinostat; XL-019; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19455266

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

    , Rosuvastatin calcium, RWJ-676070; SAR-109659, Sitagliptin phosphate monohydrate, Sorafenib, Stavudine/Lamivudine/Nevirapine, Sunitinib malate; Tadalafil, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Teriparatide, Tigecycline, Tiotropium bromide, Tipifarnib, Tipranavir, Tocilizumab, Trifluridine/TPI; UP-780; Vandetanib, Vardenafil hydrochloride hydrate, Vatalanib succinate, Vitespen, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:19536362

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    , travoprost; UCN-01; Vardenafil hydrochloride hydrate; XB-947; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:15605126

  4. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-10-01

    , Solifenacin succinate, Sunitinib malate; Tadalafil, Talnetant, Tanespimycin, Taxus, Tegaserod maleate, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, tgAAC-94, Tiotropium bromide, Tocilizumab, Tolvaptan, Trimethoprim; Vardenafil hydrochloride hydrate, Vatalanib succinate, Vinflunine, Voriconazole, VX-680; XL-880; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:18040531

  5. Collection of hematopoietic stem cells after previous radioimmunotherapy is feasible and does not impair engraftment after autologous stem cell transplantation in follicular lymphoma.

    PubMed

    Derenzini, Enrico; Stefoni, Vittorio; Maglie, Roberto; Casadei, Beatrice; Pellegrini, Cinzia; Broccoli, Alessandro; Stefani, Giulia; Fanti, Stefano; Motta, Maria Rosa; Narducci, Riccardo; Argnani, Lisa; Zinzani, Pier Luigi

    2013-12-01

    Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CHOP-like regimens, 21 patients received R-FM (rituximab-fludarabine-mitoxantrone), and 13 patients received RIT before HSC mobilization. Median CD34+ cell yield at first mobilization was 7.2 × 10(6)/kg in the R-CHOP group versus 4.3 in the R-FM group versus 1.7 in the RIT group (P = .02 R-CHOP versus R-FM; P < .0001 R-CHOP versus RIT; P < .02 R-FM versus RIT). Although 8 of 13 patients initially failed to collect enough HSC after RIT, a second and/or salvage harvest was successfully performed in 7 patients, with 10 of 13 patients (77%) finally undergoing autologous stem cell transplantation (ASCT). No differences in engraftment kinetics were observed between the three groups (R-CHOP versus R-FM versus RIT). Although mobilization was significantly impaired in patients previously treated with RIT, a salvage HSC harvest and ASCT after RIT were safe and feasible in most patients. PMID:24055654

  6. Long-term outcomes of patients with persistent indolent B cell malignancies undergoing nonmyeloablative allogeneic transplantation.

    PubMed

    Cassaday, Ryan D; Storer, Barry E; Sorror, Mohamed L; Sandmaier, Brenda M; Guthrie, Katherine A; Maloney, David G; Rajendran, Joseph G; Pagel, John M; Flowers, Mary E; Green, Damian J; Rezvani, Andrew R; Storb, Rainer F; Press, Oliver W; Gopal, Ajay K

    2015-02-01

    Relapse is least common in patients with indolent B cell (iB) malignancies (ie, iB non-Hodgkin lymphoma [NHL]) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR before NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease before NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small/chronic lymphocytic lymphoma (n = 62) and follicular lymphoma (n = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 patients (20%) who more frequently had chemoresistant disease (81% versus 39%, P = .003), disease bulk > 5 cm (61% versus 15%, P < .001), thrombocytopenia < 25k/μL (33% versus 7%, P = .002), and Hematopoietic Cell Transplant Comorbidity Index scores ≥ 3 (72% versus 37%, P = .006). After adjusting for these imbalances, RIT-treated patients had improved rates of progression-free survival (PFS) (hazard ratio [HR] = .4; 95% confidence interval [CI], .2 to .9, P = .02) and overall survival (OS) (HR = .3; 95% CI, .1 to .8, P = .008) compared with the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87% versus 44% and 59%, respectively. The use of RIT was the only factor independently associated with improved PFS and OS. Rates of nonrelapse mortality and graft-versus-host disease (GVHD) were similar between the 2 groups, although over 70% of patients developed clinically significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent i

  7. Long-Term Outcomes of Patients with Persistent Indolent B-cell Malignancies Undergoing Nonmyeloablative Allogeneic Transplantation

    PubMed Central

    Cassaday, Ryan D.; Storer, Barry E.; Sorror, Mohamed L.; Sandmaier, Brenda M.; Guthrie, Katherine A.; Maloney, David G.; Rajendran, Joseph G.; Pagel, John M.; Flowers, Mary E.; Green, Damian J.; Rezvani, Andrew R.; Storb, Rainer F.; Press, Oliver W.; Gopal, Ajay K.

    2015-01-01

    Relapse is least common in patients with indolent B-cell malignancies (iB-NHL) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR prior to NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia (CLL) treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease prior to NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small lymphocytic lymphoma/CLL (N = 62) and follicular lymphoma (N = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 (20%), who more frequently had chemoresistant disease (81% vs 39%, P = 0.003), disease bulk >5 cm (61% vs 15%, P <0.001), thrombocytopenia <25k/µL (33% vs 7%, P = 0.002), and Hematopoietic Cell Transplant Comorbidity Index scores of ≥3 (72% vs 37%, P = 0.006). After adjusting for these imbalances, RIT-treated patients had improved PFS (HR = 0.4, 95% CI: 0.2–0.9, P = 0.02) and OS (HR = 0.3, 95% CI: 0.1–0.8, P = 0.008) compared to the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87%, vs 44% and 59% (respectively). The use of RIT was the only factor independently associated with improved PFS and OS. Rates of non-relapse mortality and graft-versus-host disease (GVHD) were similar between the two groups, though over 70% of patients developed clinically-significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent iB-NHL can derive durable benefit from NMAT. PMID:25445025

  8. Radioimmunotherapy and Autologous Stem-Cell Transplantation in the Treatment of B-Cell Non-Hodgkin Lymphoma.

    PubMed

    Shimoni, Avichai; Zwas, Shifra Tzila

    2016-03-01

    High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is the standard therapy for patients with chemosensitive-relapsed or chemosensitive-refractory aggressive lymphoma. The use of rituximab, an anti-CD20 monoclonal antibody, has dramatically changed the outcome of patients with aggressive lymphoma, increasing both response and survival rates. However, despite this progress a significant proportion of patients are still refractory or relapse after frontline rituximab-containing therapy. Moreover, it is increasingly more difficult to rescue these patients with current salvage chemotherapy and ASCT approaches. Novel approaches are needed for these high-risk patients, especially in the rituximab era. Radioimmunotherapy (RIT) is a form of targeted therapy using the parent monoclonal antibody to deliver radiation emitted by a conjugated radioisotope, to the vicinity of antigen-positive tissues. Two radioimmunoconjugates--yttrium-90 ibritumomab tiuxetan (Zevalin) and iodine-131 tositumomab (Bexxar) have been in clinical use. There are multiple studies demonstrating the safety and efficacy of both agents in both indolent and aggressive lymphoma. Radiolabeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. RIT targets radiation to disease sites while limiting exposure of uninvolved critical organs, thus it can safely replace total-body irradiation during conditioning for ASCT. The major toxicity and limiting factor in RIT is myelotoxicity that is easily reversed by stem-cell rescue. RIT can be combined at standard doses with high-dose chemotherapy or can be given in escalated doses either alone or with high-dose chemotherapy before ASCT. Several phase II studies have shown the safety and potential efficacy of both agents using these approaches. A small randomized study comparing standard-dose Zevalin with combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) high-dose chemotherapy and BEAM alone suggested a

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    -globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent. PMID:17136234

  10. Preparation of functional human factor V111 in mammalian cells using methotrexate based selection

    SciTech Connect

    Capon, D.J.; Lawn, R.M.; Levinson, A.D.; Vehar, G.A.; Wood, W.I.

    1990-10-23

    This patent describes a process for producing factor VII. It comprises: cotransfecting a mammalian host cell with a DNA sequence encoding factor VIII, a second DNA sequence encoding an amplifiable marker, and a third DNA sequence encoding a selectable marker; growing the transfected cell in a non-selection medium and selecting for such selectable marker resistant cells; and amplifying the amplifiable marker DNA sequence by culturing the selected cells in media containing increasing amounts of selection agent, wherein the host cell is not deficient in the amplifiable marker.

  11. CO adsorption and kinetics on well-characterized Pd films on Pt(111) in alkaline solutions

    SciTech Connect

    Arenz, M.; Stamenkovic, V.; Wandelt, K.; Ross, P.N.; Markovic, N.M.

    2002-01-01

    The electrochemistry of CO on a bare Pt(111) electrode as well as a Pt(111) electrode modified with pseudomorphic thin palladium films has been studied in alkaline solution by means of Fourier transform infrared (FTIR) spectroscopy. First Pd films were prepared and well characterized in UHV and subsequently transferred into the electrochemical cell for the registration of the voltammetric profiles. The charge corresponding to the formation of underpotentially deposited hydrogen (H{sub upd}) on these Pt(111)-xPd surfaces was established in sulfuric acid solution as a function of x (0 {le} x {le} 1 Pd monolayer (ML)). All subsequent measurements were then performed on electrochemically deposited palladium films using the above H{sub upd}-charge vs. Pd coverage relationship to evaluate the amount of electrochemically deposited palladium. FTIR spectra for CO adsorbed on one monolayer and a submonolayer coverage are compared to those of the unmodified Pt(111) surface, all surfaces having identical 2D lattice structures. Infrared absorption bands of CO bound on either Pt(111) or Pt(111)-1ML Pd are clearly distinguished. Spectra of CO adsorbed on Pd submonolayers show characteristic features of both CO bound to Pt and to Pd, indicating that on Pt(111)-xPd surfaces there is no coupling between Pt-CO{sub ad} and Pd-CO{sub ad} molecules. The kinetics of CO oxidation on these surfaces is determined either by rotating disk electrode (RDE) measurements or by FTIR spectroscopy, monitoring the CO{sub 3}{sup 2-} production. The oxidation of CO{sub ad} on Pt(111) and on Pd modified platinum surfaces starts at the same potential, ca. at 0.2 V. The oxidation rate is, however, considerably lower on the Pt(111)-xPd surfaces than on the Pt(111) surface. The kinetics of CO oxidation appears to be determined by the nature of adsorbed hydroxyl anions (OH{sub ad}), which are more strongly (less active) adsorbed on the highly oxophilic Pd atoms.

  12. Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination.

    PubMed

    Stacey, Nicola J; Kuromori, Takashi; Azumi, Yoshitaka; Roberts, Gethin; Breuer, Christian; Wada, Takuji; Maxwell, Anthony; Roberts, Keith; Sugimoto-Shirasu, Keiko

    2006-10-01

    The Spo11 protein is a eukaryotic homologue of the archaeal DNA topoisomerase VIA subunit (topo VIA). In archaea it is involved, together with its B subunit (topo VIB), in DNA replication. However, most eukaryotes, including yeasts, insects and vertebrates, instead have a single gene for Spo11/topo VIA and no homologues for topo VIB. In these organisms, Spo11 mediates DNA double-strand breaks that initiate meiotic recombination. Many plant species, in contrast to other eukaryotes, have three homologues for Spo11/topo VIA and one for topo VIB. The homologues in Arabidopsis, AtSPO11-1, AtSPO11-2 and AtSPO11-3, all share 20-30% sequence similarity with other Spo11/topo VIA proteins, but their functional relationship during meiosis or other processes is not well understood. Previous genetic evidence suggests that AtSPO11-1 is a true orthologue of Spo11 in other eukaryotes and is required for meiotic recombination, whereas AtSPO11-3 is involved in DNA endo-reduplication as a part of the topo VI complex. In this study, we show that plants homozygous for atspo11-2 exhibit a severe sterility phenotype. Both male and female meiosis are severely disrupted in the atspo11-2 mutant, and this is associated with severe defects in synapsis during the first meiotic division and reduced meiotic recombination. Further genetic analysis revealed that AtSPO11-1 and AtSPO11-2 genetically interact, i.e. plants heterozygous for both atspo11-1 and atspo11-2 are also sterile, suggesting that AtSPO11-1 and AtSPO11-2 have largely overlapping functions. Thus, the three Arabidopsis Spo11 homologues appear to function in two discrete processes, i.e. AtSPO11-1 and AtSPO11-2 in meiotic recombination and AtSPO11-3 in DNA replication. PMID:17018031

  13. Extreme confinement of xenon by cryptophane-111 in the solid state.

    PubMed

    Joseph, Akil I; Lapidus, Saul H; Kane, Christopher M; Holman, K Travis

    2015-01-26

    Solids that sorb, capture and/or store the heavier noble gases are of interest because of their potential for transformative rare gas separation/production, storage, or recovery technologies. Herein, we report the isolation, crystal structures, and thermal stabilities of a series of xenon and krypton clathrates of (±)-cryptophane-111 (111). One trigonal crystal form, Xe@111⋅y(solvent), is exceptionally stable, retaining xenon at temperatures of up to about 300 °C. The high kinetic stability is attributable not only to the high xenon affinity and cage-like nature of the host, but also to the crystal packing of the clathrate, wherein each window of the molecular container is blocked by the bridges of adjacent containers, effectively imprisoning the noble gas in the solid state. The results highlight the potential of discrete molecule materials exhibiting intrinsic microcavities or zero-dimensional pores. PMID:25504739

  14. Kinetics and distribution of /sup 111/In-labeled platelets in patients with homocystinuria

    SciTech Connect

    Hill-Zobel, R.L.; Pyeritz, R.E.; Scheffel, U.

    1982-09-23

    Homocystinuria is an inborn error of metabolism involving a high incidence of thromboembolism. It sometimes improves with large doses of pyridoxine. We investigated the kinetics and distribution of /sup 111/Indoxine-labeled platelets in 11 normal volunteers and 12 patients with homocystinuria, none of whom had clinical evidence of acute thrombosis at the time of the study. Six of the patients were resistant to pyridoxine and had homocystinemia. There were no statistical differences in mean platelet-survival times between pyridoxine responders and nonresponders or between normal subjects and pyridoxine responders or nonresponders, regardless of whether a linear, exponential, or multiple-hit model was used to analyze the kinetic data. Plasma homocystine levels had no apparent effect on mean platelet-survival time. There was no abnormal accumulation of platelets in any of the patients, and the distribution of platelets in liver and spleen was similar to that in normal subjects. Our results suggest that the kinetics and distribution of platelets in patients with homocystinuria who have no clinical evidence of thromboembolism are normal. Thus, the data do not provide evidence for disordered platelet function or for an ongoing interaction of platelets with vessel walls in this condition.

  15. Sensitivity of scintigraphy with /sup 111/In-lymphocytes for detection of cardiac allograft rejection

    SciTech Connect

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. 3d.

    1988-12-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively.

  16. Interface dipoles of organic molecules on Ag(111) in hybrid density-functional theory

    NASA Astrophysics Data System (ADS)

    Hofmann, Oliver T.; Atalla, Viktor; Moll, Nikolaj; Rinke, Patrick; Scheffler, Matthias

    2013-12-01

    We investigate the molecular acceptors 3,4,9,10-perylene-tetracarboxylic acid dianhydride (PTCDA), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) and 4,5,9,10-pyrenetetraone (PYTON) on Ag(111) using density-functional theory (DFT). For two groups of the Heyd-Scuseria-Ernzerhof (HSE(α, ω)) family of exchange-correlation functionals (ω = 0 and 0.2 Å) we study the isolated components as well as the combined systems as a function of the amount of exact-exchange (α). We find that hybrid functionals favour electron transfer to the adsorbate. Comparing with experimental work function data, for α ≈ 0.25 we report a notable but small improvement over (semi) local functionals for the interface dipole. Although Kohn-Sham eigenvalues are only approximate representations of ionization energies, incidentally, at this value also the density of states agrees well with the photoelectron spectra. However, increasing α to values for which the energy of the lowest unoccupied molecular orbital matches the experimental electron affinity in the gas phase worsens both the interface dipole and the density of states. Our results imply that semi-local DFT calculations may often be adequate for conjugated organic molecules on metal surfaces and that the much more computationally demanding hybrid functionals yield only small improvements.

  17. Thermal effects on electronic properties of CO/Pt(111) in water.

    PubMed

    Duan, Sai; Xu, Xin; Luo, Yi; Hermansson, Kersti; Tian, Zhong-Qun

    2013-08-28

    Structure and adsorption energy of carbon monoxide molecules adsorbed on the Pt(111) surfaces with various CO coverages in water as well as work function of the whole systems at room temperature of 298 K were studied by means of a hybrid method that combines classical molecular dynamics and density functional theory. We found that when the coverage of CO is around half monolayer, i.e. 50%, there is no obvious peak of the oxygen density profile appearing in the first water layer. This result reveals that, in this case, the external force applied to water molecules from the CO/Pt(111) surface almost vanishes as a result of the competitive adsorption between CO and water molecules on the Pt(111) surface. This coverage is also the critical point of the wetting/non-wetting conditions for the CO/Pt(111) surface. Averaged work function and adsorption energy from current simulations are consistent with those of previous studies, which show that thermal average is required for direct comparisons between theoretical predictions and experimental measurements. Meanwhile, the statistical behaviors of work function and adsorption energy at room temperature have also been calculated. The standard errors of the calculated work function for the water-CO/Pt(111) interfaces are around 0.6 eV at all CO coverages, while the standard error decreases from 1.29 to 0.05 eV as the CO coverage increases from 4% to 100% for the calculated adsorption energy. Moreover, the critical points for these electronic properties are the same as those for the wetting/non-wetting conditions. These findings provide a better understanding about the interfacial structure under specific adsorption conditions, which can have important applications on the structure of electric double layers and therefore offer a useful perspective for the design of the electrochemical catalysts. PMID:23835901

  18. Enhancement of spontaneous mitotic recombination by the meiotic mutant spo11-1 in Saccharomyces cerevisiae

    SciTech Connect

    Bruschi, C.V.; Esposito, M.S.

    1983-12-01

    Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing recombination and increasing nondisjunction. The mitotic effects are not distributed equally in all chromosomal regions. The genotypes of mitotic recombinants in spo11-1/spo11-1 diploid cells provide further evidence that widely spaced chromosomal markers undergo coincident conversion in mitosis.

  19. Self-Assembly of Tetraphenyldibenzoperiflanthene (DBP) Films on Ag(111) in the Monolayer Regime.

    PubMed

    Kirchhuebel, Tino; Gruenewald, Marco; Sojka, Falko; Kera, Satoshi; Bussolotti, Fabio; Ueba, Takahiro; Ueno, Nobuo; Rouillé, Gaël; Forker, Roman; Fritz, Torsten

    2016-03-01

    Tetraphenyldibenzoperiflanthene (DBP) is a promising candidate as a component of highly efficient organic photovoltaic cells and organic light-emitting diodes. The structural properties of thin films of this particular lander-type molecule on Ag(111) were investigated by complementary techniques. Highly ordered structures were obtained, and their mutual alignment was characterized by means of low-energy electron diffraction (LEED). Scanning tunneling microscopy (STM) images reveal two slightly different arrangements within the first monolayer (ML), both describable as specific herringbone patterns with two molecules per unit cell whose dibenzoperiflanthene framework is parallel to the surface. In contrast, single DBP molecules in the second ML were imaged with much higher intramolecular resolution, resembling the shape of the frontier orbitals in the gas phase as calculated by means of density functional theory (DFT). Further deposition leads to the growth of highly ordered bilayer islands on top of the first ML with identical unit cell dimensions and orientation but slightly inclined molecules. This suggests that the first ML acts as a template for the epitaxial growth of further layers. Simultaneously, a significant number of second-layer molecules mainly located at step edges or scattered over narrow terraces do not form highly ordered aggregates. PMID:26844381

  20. Functional fecal retention visualized by (111)In-DTPA colon transit scintigraphy.

    PubMed

    Infante, Jose Rafael; Rayo, Juan I; Serrano, Justo; Dominguez, Maria L; Garcia, Lucia; Moreno, Manuel

    2015-06-01

    Constipation is an extremely common problem in children, varying from mild and short-lived to severe and chronic. Chronic constipation is a serious childhood condition and requires further investigation, including blood test, colonoscopy, radio-opaque marker study, and/or scintigraphy. We present small bowel and colon transit scintigraphy of a 14-year-old girl with history of chronic constipation, abdominal pain, weight loss, and poor response to medical treatment. After oral administration of In-DTPA in water, planar and SPECT/CT images showed normal small bowel transit time and functional fecal retention in colon transit study. PMID:25706788

  1. 111 In-labeled leukocytes in the detection of prosthetic vascular graft infections

    SciTech Connect

    Williamson, M.R.; Boyd, C.M.; Read, R.C.; Thompson, B.W.; Barnes, R.W.; Shah, H.R.; Balachandran, S.; Ferris, E.J.

    1986-07-01

    Making a clinical diagnosis of infection in prosthetic vascular grafts is difficult but when undiagnosed, this condition has a high mortality rate. Using Indium-111-labeled white-blood cells, 30 scans were performed in 21 patients suspected of having a prosthetic graft infection. The diagnosis of infected graft was confirmed by surgery in all cases, and lack of infection was established by resolution of symptoms with conservative therapy. Twenty-four hour scans of autologous Indium-111 leukocytes were obtained, and correlative CT studies were done in 11 cases. There were 13 infected grafts at surgery (purulent material present), and scans were positive in all (100% sensitivity); of 17 scans, there were 15 true negatives and two false positives (88% specificity). Using the criteria of gas or fluid around the graft, the sensitivity of CT was only 37% in a small subset of these patients. One-half of the cases in which infection was suspected clinically had no infection and had negative scans. Various types of grafts and graft materials were used, and there was no correlation with presence or absence of infection on the basis of the type of graft. Extragraft infection sites were found in five patients. In conclusion, use of Indium-111 leukocytes has been found to be an accurate and valuable diagnostic method for evaluation of suspected prosthetic vascular graft infection, and to have higher diagnostic accuracy than CT.

  2. BK Nephritis and Venous Thrombosis in Renal Transplant Recipient Detected by 111In Leukocyte Imaging.

    PubMed

    Pucar, Darko; Klein, Kandace; Corley, James; Williams, Hadyn T

    2015-07-01

    Three months after deceased donor kidney transplant, a patient who presented with proteinuric renal dysfunction and fever of undetermined origin was found to have BK viruria by quantitative polymerase chain reaction analysis. An ¹¹¹In leukocyte scan showed increased renal transplant uptake consistent with nephritis and linear uptake in the knee. Venous duplex ultrasound revealed acute occlusive thrombosis in the superficial right lesser saphenous vein in the area of increased radiolabeled leukocyte uptake. This ¹¹¹In leukocyte scan performed for fever of undetermined origin demonstrated findings of BK nephritis in a renal transplant patient and associated acute venous thrombosis related to leukocyte colonization. PMID:26018698

  3. Optical spin- and current-injection study on Si(111)-In surfaces

    NASA Astrophysics Data System (ADS)

    Arzate, N.; Vázquez-Nava, R. A.; Mendoza, Bernardo S.

    2014-11-01

    We present a theoretical study of the optical generation of one-photon spin and current injection onto In-adsorbed Si(111) surfaces with 4 ×2 and 8 ×2 reconstructions. The spin injection, under incidence of circularly polarized light into nonmagnetic semiconductors, creates spin-polarized electrons in the conduction bands. The current injection is a nonlinear second-order effect that is allowed in materials without inversion symmetry. In bulk centrosymmetric crystals, the optical injection of current can only be observed at the surface wherein the inversion of symmetry might be broken. We report calculations for the degree of spin polarization and current-injection spectra which are calculated in a full electronic band structure scheme at the level of GW scissor-energy correction. Our results show an anisotropic behavior of the spin- and current-injection optical response. We obtain maximum percentages of the degree of spin polarization of 30% and 35% for the 4 ×2 and 8 ×2 surface reconstructions, respectively. It is also possible to optically generate injection current coming mainly from the first two top layers on both In-adsorbed surface reconstructions.

  4. Time differential perturbed angular correlation of 111In-EDTA linked to the single free cysteine of bovine serum albumin.

    PubMed

    Ceolín, M; Martínez, J A; Ermácora, M R

    1997-09-25

    By means of a facile chemical modification of the bovine serum albumin molecule, it was possible to measure its hydrodynamic radius with high accuracy (approximately 3%) using the TDPAC technique. The new approach presented here allows a wide use of the TDPAC technique to perform high precision studies of backbone dynamics of almost any protein. PMID:9350519

  5. Electro-oxidation of methanol on Pt(111) in acid solutions: effects of electrolyte anions during electrocatalytic reactions

    NASA Astrophysics Data System (ADS)

    Ogasawara, Hirohito; Ito, Masatoki

    1995-10-01

    The electro-oxidation of methanol on a Pt(111) surface in both sulfuric and perchloric acid solutions was investigated by combined apparatus under both ultra-high vacuum and electrochemical environments. In sulfuric acid solution, a strong lateral interaction was observed between adsorbed bisulfate and CO derived from methanol. Coadsorption of CO derived from methanol with bisulfate ion yielded a (√7 × √7)-R19.1°-CO-bisulfate structure. In perchloric acid solution, however, no lateral interaction between adsorbed CO and perchlorate was seen. The difference in reaction rates of methanol oxidation in both solutions was explained by these specific anion adsorption effects.

  6. Hyperfine magnetic field on Cd-111 in Heusler alloys Co2MnZ (Z = Si, Ga, Ge, Sn)

    NASA Technical Reports Server (NTRS)

    Jha, S.; Mitros, C.; Lahamer, Amer; Yehia, Sherif; Julian, Glenn M.

    1989-01-01

    The time differential perturbed angular correlation method has been used to measure, as a function of temperature, the hyperfine magnetic field at Cd sites in the Heusler alloys Co2MnZ (Z = Si, Ga, Ge, Sn). The hyperfine fields, normalized to the total magnetic moment per formula unit, show an approximately linear trend toward more positive values with increasing lattice parameter.

  7. The effect of specific chloride adsorption on the electrochemicalbehavior of ultrathin Pd films deposited on Pt(111) in acidsolution

    SciTech Connect

    arenz@thch.uni-bonn.de

    2002-10-01

    The electrochemical behavior of thin Pd films supported on a Pt(111) electrode is investigated by cyclic voltammetry (CV) and in-situ Fourier transform infrared (FTIR) spectroscopy. It is demonstrated that in perchloric acid solution underpotential deposition of hydrogen (H{sub upd}) and hydroxyl adsorption (OH{sub ad}) is in strong competition with the adsorption of Cl- anions, the latter being present as a trace impurity in HClO{sub 4}. The interaction of Cl- with Pd is rather strong, controlling the adsorption of H{sub upd} and OH{sub ad} as well as the kinetic rate of CO oxidation. The microscopic insight (the binding sites) of the adsorbed CO (CO{sub ad}) and the rate of CO oxidation (established from CO2 production) on Pt(111) modified with a (sub)monolayer of Pd is elucidated by means of Fourier infrared (FTIR) spectroscopy. The appearance of both the characteristic Pt(111)-CO{sub ad} and Pt(111)1 ML Pd-CO{sub ad} stretching bands on a Pt(111) surface covered by 0.5 ML Pd confirms previous findings that the Pd atoms agglomerate into islands and that the bare Pt areas and the Pd islands behave according to their own surface chemistry. The systematic increase of the Pd surface coverage results in a gradual change in the catalytic properties of Pt(111)-xPd electrodes towards CO oxidation, from those characteristic of bare Pt(111) to those which are characteristic for Pt(111) covered with 1 ML of Pd.

  8. Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model.

    PubMed

    Ostrovskaya, R U; Romanova, G A; Barskov, I V; Shanina, E V; Gudasheva, T A; Victorov, I V; Voronina, T A; Seredenin, S B

    1999-09-01

    Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia. PMID:10780261

  9. Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress.

    PubMed

    Andreeva, N A; Stel'mashuk, E V; Isaev, N K; Ostrovskaya, R U; Gudasheva, T A; Viktorov, I V

    2000-10-01

    Argon anoxia and glucose deprivation were used for modeling of ischemic damage in the cultures of cerebellar granule cells. Protective effect of peptide piracetam analogue GVS-111 was demonstrated. GVS-111 prevented neurodegeneration induced by glutamate and oxidative stress. In contrast to GVS-111, piracetam did not attenuate neurocytotoxic effect of glutamate. PMID:11177296

  10. Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex.

    PubMed

    Romanova, G A; Mirzoev, T K; Barskov, I V; Victorov, I V; Gudasheva, T A; Ostrovskaya, R U

    2000-09-01

    Antiamnestic effect of acyl-prolyl-containing dipeptide GVS-111 was demonstrated in rats with bilateral compression-induced damage to the frontal cortex. Both intraperitoneal and oral administration of the dipeptide improved retrieval of passive avoidance responses in rats with compression-induced cerebral ischemia compared to untreated controls. PMID:11177261

  11. [The effect of the new nootropic dipeptide GVS-111 in different functional disorders of the escape reaction].

    PubMed

    Inozemtsev, A N; Trofimov, S S; Borlikova, G G; Firova, F A; Pragina, L L; Gudasheva, T A; Ostrovskaia, R U; Tushmalova, N A; Voronina, T A

    1998-01-01

    The authors studied the effect of a new nootropic agent with anxiolytic properties GVS-111 (ethyl ether N-phenylacetyl-L-prolylglycine) on formation of the avoidance reaction (AR) in rats and its functional disorders which were induced by two methods. In one case the stereotype of the relations between the stimulus, reaction and its consequence which developed during the experiment were urgently disturbed: the change of the animal to the other half of the chamber in response to a conditioned stimulus did not lead to its cutting off and prevention of the electropain stimulation for three successive combinations (AR error). In another case the spatial stereotype of the experiment was altered by changing the place of the opening through which the animal avoided the stimulus (spatial remodeling). Intraperitoneal injection of GVS-111 (0.1 mg/kg/day) improved the learning, but the effect differed from experiment to experiment. Along with this, the dipeptide prevented AR disturbance during the error and quickened restoration of the habit in spatial remodeling. It was shown earlier that AR disorders during an error are prevented by anxiolytics and nootropic agents but during spatial remodeling only by nootropic agents. It may be assumed that the positive effect of GSV-111 on AR in functional disorders is due to its nootropic effect. PMID:9690067

  12. Vapor space characterization of waste Tank 241-C-111 (in situ): Results from samples collected on 6/20/94

    SciTech Connect

    Ligotke, M.W.; Pool, K.H.; Lucke, R.B.; McVeety, B.D.; Clauss, T.W.; McCulloch, M.; Young, J.S.; Fruchter, J.S.; Goheen, S.C.

    1995-10-01

    This report describes inorganic and organic analyses results from in situ samples obtained from the headspace of the Hanford waste storage Tank 241-C-111 (referred to as Tank C-111). The results described here were obtained to support safety and toxicological evaluations. A summary of the results for inorganic and organic analytes is listed in Summary Table 1. Detailed descriptions of the results appear in the text. Quantitative results were obtained for the inorganic compounds ammonia (NH{sub 3}), nitrogen dioxide (NO{sub 2}), nitric oxide (NO), hydrogen cyanide (HCN), and water vapor (H{sub 2}O). Sampling for sulfur oxides was not requested. Organic compounds were quantitatively determined. Five organic tentatively identified compounds (TICs) were observed above the detection limit of (ca.) 10 ppbv, but standards for most of these were not available at the time of analysis, and the reported concentrations are semiquantitative estimates. In addition, the authors looked for the 40 standard TO-14 analytes and observed 39. None of these compounds were above the 2-ppbv calibrated instrumental detection limit. However, it is believed that the detection of dichlorodifluoromethane and methyl benzene are real at these low concentrations. The five organic analytes with the highest estimated concentrations are listed in Summary Table 1. The five analytes account for approximately 100% of the total organic components in Tank C-111.

  13. Understanding the enhanced catalytic activity of Cu1@Pd3(111) in formic acid dissociation, a theoretical perspective

    NASA Astrophysics Data System (ADS)

    He, Feng; Li, Kai; Xie, Guangyou; Wang, Ying; Jiao, Menggai; Tang, Hao; Wu, Zhijian

    2016-06-01

    The bimetallic Cu1@Pd3(111) catalyst has been synthesized recently and exhibits better catalytic activity and durability compared with pure Pd(111) as anode catalyst in direct formic acid fuel cells (DFAFCs). In this work, we studied the reaction mechanism of formic acid dissociation on both Pd(111) and Cu1@Pd3(111) by using the density functional method. Our calculations showed that the surface adsorption of the poisoning species CO on Cu1@Pd3(111) is weakened mainly by the strain effect rather than the Cusbnd Pd ligand effect. The Cu1@Pd3(111) can effectively promote the catalytic activity for formic acid dissociation by decreasing the barrier of CO2 formation from the preferential trans-COOH intermediate and increasing the barrier of CO formation from the reduction of CO2. We found that the H atom accumulation, electron accumulation and low electrode potential could accelerate the catalyst deactivation due to the contamination of the poisoning species CO. Furthermore, under low anode potential, the Cu1@Pd3(111) has better durability than pure Pd(111), which can be attributed to the unfavorable CO formation and the favorable CO desorption.

  14. Dynamics of ultrathin V-oxide layers on Rh(111) in catalytic oxidation of ammonia and CO.

    PubMed

    von Boehn, B; Preiss, A; Imbihl, R

    2016-07-20

    Catalytic oxidation of ammonia and CO has been studied in the 10(-4) mbar range using a catalyst prepared by depositing ultra-thin vanadium oxide layers on Rh(111) (θV ≈ 0.2 MLE). Using photoemission electron microscopy (PEEM) as a spatially resolving method, we observe that upon heating in an atmosphere of NH3 and O2 the spatial homogeneity of the VOx layer is removed at 800 K and a pattern consisting of macroscopic stripes develops; at elevated temperatures this pattern transforms into a pattern of circular VOx islands. Under reaction conditions the neighboring VOx islands become attracted by each other and coalesce. Similar processes of pattern formation and island coalescence are observed in catalytic CO oxidation. Reoxidation of the reduced VOx catalyst proceeds via surface diffusion of oxygen adsorbed onto Rh(111). A pattern consisting of macroscopic circular VOx islands can also be obtained by heating a Rh(111)/VOx catalyst in pure O2. PMID:27380822

  15. Flow-velocity data collected in the wetlands adjacent to canal C-111 in south Florida during 1997 and 1999

    USGS Publications Warehouse

    Ball, Maria H.; Schaffranek, Raymond W.

    2000-01-01

    The U.S. Geological Survey (USGS) is working closely with other Federal and State agencies in a comprehensive program to evaluate and restore the south Florida ecosystem. Within the USGS South Florida Ecosystem Program, a project entitled 'Coupling Models for Canal and Wetland Flow/Transport Interaction' is focused on analysis and numerical simulation of flow and potential transport of constituents between canal C-111 and wetlands adjacent to Everglades National Park. In support of this project, comprehensive sets of flow, vegetation, and water-quality data were collected in September 1997 and 1999. The flow-velocity data are compiled, summarized, and tabulated in this report. The flow, vegetation, and water-quality data are available for downloading from the World Wide Web.

  16. Case 227: Endobronchial Carcinoid Tumor with Incidental Metastatic Breast Cancer Detected with Somatostatin Receptor Scintigraphy ((111)In Pentreotide).

    PubMed

    Raslan, Osama A; Parkar, Nadeem D; Muzaffar, Razi; Doherty, Christina; Osman, Medhat M

    2016-03-01

    History A 30-year-old woman with polycystic ovarian syndrome who was undergoing hormone replacement therapy presented with a 6-month history of a nonproductive cough and a 1-day history of hemoptysis (approximately 20 mL). Intravenous contrast material-enhanced (100 mL of Omnipaque 350; GE Healthcare, Princeton, NJ) computed tomographic (CT) pulmonary angiography was performed to evaluate for pulmonary embolism. On the basis of the CT pulmonary angiographic findings, chromogranin A and 5-hydroxyindoleacetic acid levels were measured and were 7 nmol/L (343 µg/L) (high) and 2.9 mg per 24 hours (15.167 µmol/d) (normal), respectively. This patient underwent bronchoscopy and biopsy. After these tests, she was referred for whole-body scintigraphy, which revealed an unexpected finding that was further investigated with fluorine 18 ((18)F) flurodeoxyglucose (FDG) positron emission tomography (PET) and CT. PMID:26885736

  17. Class II human leucocyte antigen DRB1*11 in hairy cell leukaemia patients with and without haemolytic uraemic syndrome

    PubMed Central

    Arons, Evgeny; Adams, Sharon; Venzon, Venzon, David J; Pastan, Ira; Kreitman, Robert J.

    2014-01-01

    Frequencies of human leucocyte antigens (HLA) were determined in 287 classic hairy cell leukaemia (HCL) patients. With respect to both population (n=287) and allele (2n=574) frequency, respectively, the most common HLA class I and II antigens expressed were HLA-A*02 (49.1% and 28.6%), HLA-B*07 (21.3% and 11.1%), HLA-C*07 (46.7 and 28.2%), HLA-DQB1*03 (62.7% and 37.3%), HLA-DRB1*11 (30.0% and 16.0%) and HLA-DRB4*01 (45.3% and 29.6%). In comparing 6–14 databases of control Caucasians to 267 Caucasian HCL patients, only HLA-DRB1*11 was consistently over-represented in HCL, 31.1% of patients vs 17–19.9% of controls (p=0.0055 to <0.0001) and 16.5% of alleles vs 6.5–12.3% of control alleles (p=0.022 to <0.0001). HLA-DRB1*11 is a known risk factor for acquired thrombotic microangiopathy. Anti-CD22 recombinant immunotoxin BL22 in HCL was associated with a 12% incidence of completely reversible grade 3–4 haemolytic uraemic syndrome (HUS), mainly during the second or third retreatment cycle. Of 49 HCL patients receiving ≥2 cycles of BL22, 7 (14%) had HUS and HLA-DRB1*11 was expressed in 71% of 7 with HUS compared with only 21% of 42 without (p=0.015). These data suggest that DBR1*11 may be a marker for increased susceptibility to HCL and, among HCL patients, could be a risk factor for BL22-induced HUS. PMID:24931452

  18. In Situ Scanning Tunneling Microscopy Topography Changes of Gold (111) in Aqueous Sulfuric Acid Produced by Electrochemical Surface Oxidation and Reduction and Relaxation Phenomena

    NASA Astrophysics Data System (ADS)

    Pasquale, M. A.; Nieto, F. J. Rodríguez; Arvia, A. J.

    The electrochemical formation and reduction of O-layers on gold (111) films in 1 m sulfuric acid under different potentiodynamic routines are investigated utilizing in situ scanning tunneling microscopy. The surface dynamics is interpreted considering the anodic and cathodic reaction pathways recently proposed complemented with concurrent relaxation phenomena occurring after gold (111) lattice mild disruption (one gold atom deep) and moderate disruption (several atoms deep). The dynamics of both oxidized and reduced gold topographies depends on the potentiodynamic routine utilized to form OH/O surface species. The topography resulting from a mild oxidative disruption is dominated by quasi-2D holes and hillocks of the order of 5 nm, involving about 500-600 gold atoms each, and their coalescence. A cooperative turnover process at the O-layer, in which the anion ad-layer and interfacial water play a key role, determines the oxidized surface topography. The reduction of these O-layers results in gold clusters, their features depending on the applied potential routine. A moderate oxidative disruption produces a surface topography of hillocks and holes several gold atoms high and deep, respectively. The subsequent reduction leads to a spinodal gold pattern. Concurrent coalescence appears to be the result of an Ostwald ripening that involves the surface diffusion of both gold atoms and clusters. These processes produce an increase in surface roughness and an incipient gold faceting. The dynamics of different topographies can be qualitatively explained employing the arguments from colloidal science theory. For 1.1 V ≤ E ≅ Epzc weak electrostatic repulsions favor gold atom/cluster coalescence, whereas for E < Epzc the attenuated electrostatic repulsions among gold surfaces stabilize small clusters over the substrate producing string-like patterns.

  19. Controlling the stress of growing GaN on 150-mm Si (111) in an AlN/GaN strained layer superlattice

    NASA Astrophysics Data System (ADS)

    Lin, Po-Jung; Huang, Shih-Yung; Wang, Wei-Kai; Chen, Che-Lin; Chung, Bu-Chin; Wuu, Dong-Sing

    2016-01-01

    For growing a thicker GaN epilayer on a Si substrate, generally, a larger wafer bowing with tensile stress caused by the mismatch of thermal expansion coefficients between GaN and Si easily generates a cracked surface during cool down. In this work, wafer bowing was investigated to control stress by changing the thickness of a GaN layer from 18.6 to 27.8 nm in a 80-paired AlN/GaN strained layer superlattice (SLS) grown on a 150-mm Si (111) substrate. The results indicated that wafer bowing was inversely proportional to the total thickness of epilayer and the thickness of the GaN layer in the AlN/GaN SLS, since higher compressive stress caused by a thicker GaN layer during SLS growth could compensate for the tensile stress generated during cool down. After returning to room temperature, the stress of the AlN/GaN SLS was still compressive and strained in the a-axis. This is due to an unintended AlGaN grading layer was formed in the AlN/GaN SLS. This AlGaN layer reduced the lattice mismatch between AlN and GaN and efficiently accumulated stress without causing relaxation.

  20. TiO 2 chemical vapor deposition on Si(111) in ultrahigh vacuum: Transition from interfacial phase to crystalline phase in the reaction limited regime

    NASA Astrophysics Data System (ADS)

    Karlsson, P. G.; Richter, J. H.; Andersson, M. P.; Johansson, M. K.-J.; Blomquist, J.; Uvdal, P.; Sandell, A.

    2011-07-01

    The interaction between the metal organic precursor molecule titanium(IV) isopropoxide (TTIP) and three different surfaces has been studied: Si(111)-(7 × 7), SiOx/Si(111) and TiO2. These surfaces represent the different surface compositions encountered during TTIP mediated TiO2 chemical vapor deposition on Si(111). The surface chemistry of the titanium(IV) isopropoxide precursor and the film growth have been explored by core level photoelectron spectroscopy and x-ray absorption spectroscopy using synchrotron radiation. The resulting film morphology has been imaged with scanning tunneling microscopy. The growth rate depends on both surface temperature and surface composition. The behavior can be rationalized in terms of the surface stability of isopropoxy and isopropyl groups, confirming that growth at 573 K is a reaction limited process.

  1. [The role of non-NMDA glutamate receptors in the EEG effects of chronic administration of noopept GVS-111 in awake rats].

    PubMed

    Kovalev, G I; Vorob'ev, V V

    2002-01-01

    Participation of the non-NMDA glutamate receptor subtype in the formation of the EEG frequency spectrum was studied in wakeful rats upon a long-term (10 x 0.2 mg/kg, s.c.) administration of the nootropic dipeptide GVS-111 (noopept or N-phenylacetyl-L-prolyglycine ethylate). The EEGs were measured with electrodes implanted into somatosensor cortex regions, hippocampus, and a cannula in the lateral ventricle. The acute reactions (characteristic of nootropes) in the alpha and beta ranges of EEG exhibited inversion after the 6th injection of noopept and almost completely vanished after the 9th injection. Preliminary introduction of the non-NMDA antagonist GDEE (glutamic acid diethyl ester) in a dose of 1 mumole into the lateral ventricle restored the EEG pattern observed upon the 6th dose of GVS-111. The role of glutamate receptors in the course of a prolonged administration of nootropes, as well as the possible mechanisms accounting for a difference in the action of GVS-111 and piracetam are discussed. PMID:12596524

  2. Effect of acid adaptation and acid shock on thermal tolerance and survival of Escherichia coli O157:H7 and O111 in apple juice.

    PubMed

    Usaga, Jessie; Worobo, Randy W; Padilla-Zakour, Olga I

    2014-10-01

    Gradual exposure to moderate acidic environments may enhance the thermal tolerance and survival of Escherichia coli O157:H7 in acid and acidified foods. Limited studies comparing methodologies to induce this phenomenon have been performed. The effects of strain and physiological state on thermal tolerance and survival of E. coli in apple juice were studied. The decimal reduction time (D-value) at 56°C [D56°C] was determined for E. coli O157:H7 strains C7927 and ATCC 43895 and E. coli O111 at four physiological states: unadapted, acid-shocked (two methodologies used), and acid-adapted cells. The effect of acidulant was also evaluated by determining the D56°C for the O157:H7 strains subjected to acid shock during 18 h in Trypticase soy broth (TSB), with pH 5 adjusted with hydrochloric, lactic, and malic acids. Survival of the three strains at four physiological states was determined at 1 ± 1°C and 24 ± 2°C. Experiments were performed in triplicate. For thermal inactivation, a significant interaction was found between strain and physiological state (P < 0.0001). Highest thermal tolerance was observed for the 43895 strain subjected to acid shock during 18 h in TSB acidified with HCl (D56°C of 3.0 ± 0.1 min) and the lowest for the acid-shocked C7927 strain treated for 4 h in TSB acidified with HCl (D56°C of 0.45 ± 0.06 min). Acidulants did not alter the heat tolerance of strain C7927 (D56°C of 1.9 ± 0.1 min; P > 0.05) but significantly affected strain 43895 (P < 0.05), showing the greatest tolerance when malic acid was used (D56°C of 3.7 ± 0.3 min). A significant interaction between strain, storage temperature, and physiological state was noted during the survival experiments (P < 0.05). E. coli O111 was the most resistant strain, surviving 6 and 23 days at 24 and 1°C, respectively. Our findings may assist in designing challenge studies for juices and other pH-controlled products, where Shiga toxin-producing E. coli represents the pathogen of concern. PMID:25285481

  3. Interface and facet control during Czochralski growth of (111) InSb crystals for cost reduction and yield improvement of IR focal plane array substrates

    NASA Astrophysics Data System (ADS)

    Gray, Nathan W.; Perez-Rubio, Victor; Bolke, Joseph G.; Alexander, W. B.

    2014-10-01

    Focal plane arrays (FPAs) made on InSb wafers are the key cost-driving component in IR imaging systems. The electronic and crystallographic properties of the wafer directly determine the imaging device performance. The "facet effect" describes the non-uniform electronic properties of crystals resulting from anisotropic dopant segregation during bulk growth. When the segregation coefficient of dopant impurities changes notably across the melt/solid interface of a growing crystal the result is non-uniform electronic properties across wafers made from these crystals. The effect is more pronounced in InSb crystals grown on the (111) axis compared with other orientations and crystal systems. FPA devices made on these wafers suffer costly yield hits due to inconsistent device response and performance. Historically, InSb crystal growers have grown approximately 9-19 degree off-axis from the (111) to avoid the facet effect and produced wafers with improved uniformity of electronic properties. It has been shown by researchers in the 1960s that control of the facet effect can produce uniform small diameter crystals. In this paper, we share results employing a process that controls the facet effect when growing large diameter crystals from which 4, 5, and 6" wafers can be manufactured. The process change resulted in an increase in wafers yielded per crystal by several times, all with high crystal quality and uniform electronic properties. Since the crystals are grown on the (111) axis, manufacturing (111) oriented wafers is straightforward with standard semiconductor equipment and processes common to the high-volume silicon wafer industry. These benefits result in significant manufacturing cost savings and increased value to our customers.

  4. Enzymatic in situ saccharification of chestnut shell with high ionic liquid-tolerant cellulases from Galactomyces sp. CCZU11-1 in a biocompatible ionic liquid-cellulase media.

    PubMed

    He, Yu-Cai; Liu, Feng; Gong, Lei; Di, Jun-Hua; Ding, Yun; Ma, Cui-Luan; Zhang, Dan-Ping; Tao, Zhi-Cheng; Wang, Cheng; Yang, Bin

    2016-02-01

    In this study, it was the first time to report that the cellulases of Galactomyces sp. CCZU11-1 showed high activity and stability in the culture and reaction media containing IL [Mmim]DMP. Using untreated chestnut shell (CNS) as carbon source in the culture media containing IL [Mmim]DMP (5%, w/v), high activity of FPA (28.6U/mL), xylanase (186.2U/mL), and CMCase (107.3U/mL) were obtained, and 184.9mg/L of total protein was achieved. Furthermore, the changes in the structural features (crystallinity, morphology, and porosity) of the solid residue of CNS utilized with Galactomyces sp. CCZU11-1 were characterized with Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. After was enzymatically hydrolyzed with the prepared crude enzymes in IL diluted to 20% (w/v), a high yield of reducing sugars, 62.1%, was obtained. Significantly, Galactomyces sp. CCZU11-1 showed high potential for the efficient transformation of lignocellulosic materials to glucose in a single-step process. PMID:26642218

  5. Tumour scanning with indium-111 dihaematoporphyrin ether.

    PubMed Central

    Quastel, M. R.; Richter, A. M.; Levy, J. G.

    1990-01-01

    Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection. Images Figure 1 PMID:2147858

  6. Combined bone scintigraphy and indium-111 leukocyte scans in neuropathic foot disease

    SciTech Connect

    Schauwecker, D.S.; Park, H.M.; Burt, R.W.; Mock, B.H.; Wellman, H.N.

    1988-10-01

    It is difficult to diagnose osteomyelitis in the presence of neurotrophic osteoarthropathy. We performed combined (99mTc)MDP bone scans and indium-111 (111In) leukocyte studies on 35 patients who had radiographic evidence of neuropathic foot disease and clinically suspected osteomyelitis. The (111In)leukocyte study determined if there was an infection and the bone scan provided the anatomic landmarks so that the infection could be localized to the bone or the adjacent soft tissue. Seventeen patients had osteomyelitis and all showed increased (111In)leukocyte activity localized to the bone, giving a sensitivity of 100%. Among the 18 patients without osteomyelitis, eight had no accumulation of (111In)leukocytes, seven had the (111In)leukocyte activity correctly localized to the soft tissue, two had (111In)leukocyte activity mistakenly attributed to the bone, and one had (111In)leukocyte accumulation in a proven neuroma which was mistakenly attributed to bone. These three false-positive results for osteomyelitis reduced the specificity to 83%. Considering only the 27 patients with a positive (111In)leukocyte study, the combined bone scan and (111In)leukocyte study correctly localized the infection to the soft tissues or bone in 89%. Uninfected neurotrophic osteoarthropathy does not accumulate (111In)leukocytes. We found the combined bone scan and (111In) leukocyte study useful for the detection and localization of infection to soft tissue or bone in patients with neuropathic foot disease.

  7. Improving the In Vivo Profile of Minigastrin Radiotracers: A Comparative Study Involving the Neutral Endopeptidase Inhibitor Phosphoramidon.

    PubMed

    Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

    2016-02-01

    Minigastrin radiotracers, such as [(111)In-DOTA]MG0 ([(111)In-DOTA-DGlu(1)]minigastrin), have been considered for diagnostic imaging and radionuclide therapy of CCK2R-positive human tumors, such as medullary thyroid carcinoma. However, the high kidney retention assigned to the pentaGlu(2-6) repeat in the peptide sequence has compromised their clinical applicability. On the other hand, truncated des(Glu)(2-6)-analogs, such as [(111)In-DOTA]MG11 ([(111)In-DOTA-DGlu(10),desGlu(2-6)]minigastrin), despite their low renal uptake, show poor bioavailability and tumor targeting. [(111)In]CP04 ([(111)In-DOTA-DGlu(1-6)]minigastrin) acquired by Glu(2-6)/DGlu(2-6) substitution showed promising tumor-to-kidney ratios in rodents. In the present study, we compare the biological profiles of [(111)In]CP04, [(111)In-DOTA]MG11, and [(111)In-DOTA]MG0 during in situ neutral endopeptidase (NEP) inhibition, recently shown to improve the bioavailability of several peptide radiotracers. After coinjection of the NEP inhibitor, phosphoramidon (PA), the stability of [(111)In]CP04 and [(111)In-DOTA]MG0 in peripheral mouse blood increased, with an exceptional >14-fold improvement monitored for [(111)In-DOTA]MG11. In line with these findings, PA treatment increased the uptake of [(111)In]CP04 (8.5 ± 0.4%ID/g to 16.0 ± 2.3%ID/g) and [(111)In-DOTA]MG0 (11.9 ± 2.2%ID/g to 17.2 ± 0.9%ID/g) in A431-CCK2R(+) tumors at 4 hours postinjection, whereas the respective increase for [(111)In-DOTA]MG11 was >6-fold (2.5 ± 0.9%ID/g to 15.1 ± 1.7%ID/g). Interestingly, kidney uptake remained lowest for [(111)In-DOTA]MG11, but unfavorably increased by PA treatment for [(111)In-DOTA]MG0. Thus, overall, the most favorable in vivo profile was displayed by [(111)In-DOTA]MG11 during NEP inhibition, highlighting the need to validate this promising concept in the clinic. PMID:26844849

  8. Use of indium-111 as a red cell label

    SciTech Connect

    AuBuchon, J.P.; Brightman, A.

    1989-02-01

    To select the most promising 111In chelate for use as a second red cell (RBC) label for comparison of the survival of autologous and allogeneic cells, 49 normal RBC samples were studied in vitro after being labeled with 111In-8-hydroxyquinolinol (111In-oxine) prepared by three different methods, 111In-tropolone, and 111In-acetylacetone. Labeling efficiencies reached 99 percent and did not decline when the amount of 111In used was increased from 1.75 to 50 muCi per ml of RBCs. Storage of labeled RBCs in normal AB plasma at 4, 22, and 37 degrees C for up to 48 hours resulted in a similar rate of loss of the label from the RBCs with all labeling methods. These rates were time- and temperature-dependent and were accurate predictions of the rates found in later in vivo experimentation. Fresh RBCs from 11 subjects were labeled with 111In chelated with oxine in the presence of the RBCs or chelated with tropolone just prior to the labeling. RBC mass determinations using these autologous RBCs labeled with 111In accurately reflected the subjects' RBC masses as predicted through standard morphometric formulae. The rate of disappearance of the radionuclide after reinfusion of the autologous RBCs decreased with time. At 24 hours after reinfusion, 89.5 +/- 1.29 percent (mean +/- SEM) of the 111In-tropolone and 87.3 +/- 1.25 percent of the 111In-oxine continued in circulation. 111In is a simple and efficient agent for the labeling of RBCs for blood volume determinations and short-term survivals.

  9. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... replacements shall meet, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at the time... replaced with mirrors meeting, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at... 49 Transportation 5 2013-10-01 2013-10-01 false Rear-vision mirrors. 393.80 Section...

  10. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... replacements shall meet, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at the time... replaced with mirrors meeting, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at... 49 Transportation 5 2014-10-01 2014-10-01 false Rear-vision mirrors. 393.80 Section...

  11. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... replacements shall meet, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at the time... replaced with mirrors meeting, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at... 49 Transportation 5 2012-10-01 2012-10-01 false Rear-vision mirrors. 393.80 Section...

  12. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... replacements shall meet, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at the time... replaced with mirrors meeting, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at... 49 Transportation 5 2011-10-01 2011-10-01 false Rear-vision mirrors. 393.80 Section...

  13. Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease

    SciTech Connect

    De Faucal, P.; Peltier, P.; Planchon, B.; Dupas, B.; Touze, M.D.; Baron, D.; Scaible, T.; Berger, H.J.; Chatal, J.F. )

    1991-05-01

    The potential advantage of using {sup 111}In-antifibrin ({sup 111}In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before {sup 111}In-AF injection). All patients had contrast venography (considered as the gold standard) and {sup 111}In-AF scintigraphy within 24 hr. Two to 3 mCi of {sup 111}In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of {sup 111}In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive {sup 111}In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of {sup 111}In-AF for diagnosing DVT.

  14. Indium-111-leukocyte imaging in acute cholecystitis

    SciTech Connect

    Fink-Bennett, D.; Clarke, K.; Tsai, D.; Nuechterlein, P.; Gora, G. )

    1991-05-01

    Eleven patients with suspected acute cholecystitis underwent sequential {sup 99}mTc-iminodiacetic derivative (IDA) and {sup 111}In-white blood cell (WBC) imaging to determine if {sup 111}In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to {sup 99}mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive {sup 99}mTc-IDA and {sup 111}In-WBC, one an indeterminate {sup 111}In-WBC and true-positive {sup 99}mTc-IDA, and one a true-positive {sup 111}In-WBC and false-negative {sup 99}mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after {sup 99}mTc-IDA administration and none had {sup 111}In-WBC gallbladder wall uptake. Both {sup 111}In-WBC and {sup 99}mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and {sup 111}In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively.

  15. Mechanism of ionophoric transport of indium-111 cations through a lipid bilayer membrane

    SciTech Connect

    Choi, H.O.; Hwang, K.J.

    1987-01-01

    The use of mobile ionophores to facilitate the transport of /sup 111/In through a lipid bilayer membrane has broad applications in liposome technology and cell labeling. However, the mechanism of such ionophore-mediated transport of /sup 111/In through a lipid bilayer membrane is not completely clear. The present report describes the correlations of the behaviors of ionophoric loading of /sup 111/In into liposomes with the lipophilicity and the indium-binding affinity of three ionophores, namely, 8-hydroxyquinoline, acetylacetone, and tropolone. Our results suggest that the mechanism of the ionophoric transport of /sup 111/In through a lipid bilayer membrane involves the rapid exchange of /sup 111/In cations among the ionophores in both the aqueous solution and the lipid bilayer. Furthermore, the effectiveness of an ionophore in facilitating the transport of /sup 111/In from the external aqueous compartment to the entrapped nitrilotriacetic acid depends not only on the lipophilicity of the (/sup 111/In)ionophore complex, but also on the lipophilicity of the free ionophore itself and the competition of /sup 111/In between nitrilotriacetic acid inside the inner aqueous compartment of the liposome and the ionophore imbedded in the lipid bilayer membrane of the liposome.

  16. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... replacements shall meet, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at the time... replaced with mirrors meeting, as a minimum, the requirements of FMVSS No. 111 (49 CFR 571.111) in force at... 49 Transportation 5 2010-10-01 2010-10-01 false Rear-vision mirrors. 393.80 Section...

  17. Appearance of hyperostosis frontalis interna on indium-111 leukocyte scans: potential diagnostic pitfall

    SciTech Connect

    Floyd, J.L.; Jackson, D.E. Jr.; Carretta, R.

    1986-04-01

    The appearance of hyperostosis frontalis interna on an (/sup 111/In)leukocyte scan is reported. Recognition of the potential for normal accumulation of 111In-labeled white blood cells within this common process involving the skull is necessary to avoid misdiagnosis.

  18. Indium-111 leukocyte imaging in patients with rheumatoid arthritis

    SciTech Connect

    Uno, K.; Matsui, N.; Nohira, K.; Suguro, T.; Kitakata, Y.; Uchiyama, G.; Miyoshi, T.; Uematsu, S.; Inoue, S.; Arimizu, N.

    1986-03-01

    This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of (/sup 111/In)leukocytes. No accumulation of (/sup 111/In)leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by (/sup 111/In)leukocyte scintigraphy. There was little correlation between the stage of the disease, as determined by radiography, and (/sup 111/In)leukocyte accumulation. This study suggests that (/sup 111/In)leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response.

  19. Effect of metabolism on retention of indium-111-labeled monoclonal antibody in liver and blood

    SciTech Connect

    Kinuyfa, S.; Jeong, J.M.; Garmestani, K.

    1994-11-01

    The effect of a chelator structure on the metabolic fate of the {sup 111}In-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver. Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaacetic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with {sup 111}In-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products. The biodistribution of {sup 111}In-1B4M-T101 and {sup 111}In-CHX-B-T101 were similar to each other but significantly different from that of {sup 111}In-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact {sup 111}In-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% 1D/g for the cDTPA conjugate and 1.6% lD/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days. The thiourea linkage between T101 and the {sup 111}In-labeled chelates and a higher complex stability and higher lipophilicity of {sup 111}In-1B4M and {sup 111}In-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX conjugates. 31 refs., 3 figs., 1 tab.

  20. The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties

    SciTech Connect

    Rand, J.A.; Brown, M.L. )

    1990-10-01

    Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 ({sup 111}In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after {sup 111}In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The {sup 111}In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties.

  1. Detection of deep venous thrombosis by indium-111 leukocyte scintigraphy

    SciTech Connect

    D'Alonzo, W.A. Jr.; Alavi, A.

    1986-05-01

    Indium-111-labeled leukocyte ((/sup 111/In)WBC) scintigraphy has been used successfully for detection of inflammation. Occasionally, noninflammatory collections of white blood cells such as hematomas or hemorrhage have been localized. We report a case in which unsuspected femoral deep venous thrombosis was diagnosed on an (/sup 111/In)WBC leukocyte scan performed for detection of osteomyelitis. Readers are advised to avoid interpreting all vascular (/sup 111/In)WBC localization as necessarily infectious. This may be of particular significance in patients with vascular grafts.

  2. Characteristic local association of In impurities dispersed in ZnO

    NASA Astrophysics Data System (ADS)

    Sato, W.; Komatsuda, S.; Ohkubo, Y.

    2012-12-01

    Local environments in 0.5 at.% In-doped ZnO were investigated by means of the time-differential perturbed angular correlation (TDPAC) method. In a comparative study, using the 111Cd probe nuclei as the decay products of different parents, 111In and 111mCd, we found that 111In microscopically forms a unique structure with nonradioactive In ion(s) dispersed in ZnO, whereas 111mCd has no specific interaction with the In impurities. The spectral damping of the TDPAC spectra is attributed to the aftereffect following the EC decay of 111In. It was demonstrated from the aftereffect that the local density and/or mobility of conduction electrons at the 111In probe site in the In-doped ZnO is lowered due to the characteristic structure locally formed by the dispersed In ion(s).

  3. Persistent uptake of indium-111-antimyosin monoclonal antibody in patients with myocardial infarction

    SciTech Connect

    Matsumori, A.; Yamada, T.; Tamaki, N.; Kawai, C.; Watanabe, Y.; Yonekura, Y.; Endo, K.; Konishi, J.; Yoshida, A.; Tamaki, S. )

    1990-11-01

    Indium-111(111In)-antimyosin scintigraphy was investigated in 27 patients with myocardial infarction. {sup 111}In-antimyosin Fab was administered intravenously, and planar and single photon emission computed tomographic images were obtained 48 hours later. Uptake of {sup 111}In-antimyosin was present in 9 of 10 patients (90%) studied within 6 days of infarction. During the second week positive scans were seen in 16 of 16 patients (100%) including 13 (81%) who had normal creatine kinase levels. The mechanism of persistent positive antimyosin images in the subacute stage of myocardial infarction remains to be clarified. {sup 111}In-antimyosin scintigraphy may be useful as a noninvasive method for the detection of myocardial injury late and early after a suspected acute myocardial infarction.

  4. Lupus myocarditis: case report

    SciTech Connect

    LaManna, M.M.; Lumia, F.J.; Gordon, C.I.; Sumathisena; Maranhao, V.

    1988-03-01

    Although gallium-67 (/sup 67/Ga) accumulates in both neoplastic and inflammatory tissues, indium-111 (/sup 111/In) labeled leukocytes are seen only in inflammatory cells. Indium-111-labeled leukocytes therefore are a useful agent in the noninvasive differentiation of inflammatory tissue from neoplastic tissue. This case is an interesting example of the use of /sup 111/In-labeled leukocytes to make that differentiation.

  5. In Vivo Detection of Stem Cells Grafted in Infarcted Rat Myocardium

    PubMed Central

    Zhou, Rong; Thomas, Daniel H.; Qiao, Hui; Bal, Harshali S.; Choi, Seok-Rye; Alavi, Abass; Ferrari, Victor A.; Kung, Hank F.; Acton, Paul D.

    2008-01-01

    The evaluation of stem cell–mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of 99mTc-sestamibi to assess myocardial perfusion and of 111In-labeled stem cells to delineate stem cell engraftment. Methods Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1–14.8 MBq (0.3–0.4 mCi) of 111In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. 111In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of 99mTc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image 99mTc-sestamibi uptake simultaneously with 111In to delineate retention of 111In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. Results SPECT of 99mTc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the 111In signal from the labeled stem cells overlapped the perfusion deficits identified from the 99mTc-sestamibi images. The 111In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. Conclusion This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with 99mTc-sestamibi and with 111In-labeled stem cells grafted into the region of the infarct. PMID:15872356

  6. Comparative biodistributions of indium-111-labelled macrocycle chimeric B72.3 antibody conjugates in tumour-bearing mice.

    PubMed Central

    Turner, A.; King, D. J.; Farnsworth, A. P.; Rhind, S. K.; Pedley, R. B.; Boden, J.; Boden, R.; Millican, T. A.; Millar, K.; Boyce, B.

    1994-01-01

    A novel 111In ligand (a C-functionalised derivative of 1,4,7-triazacyclononanetriacetic acid), termed 9N3, was covalently attached to chimeric B72.3, labelled with 111In and compared with 111In-labelled chimeric B72.3 diethylenetriaminepentaacetic acid (DTPA) cyclic anhydride conjugate (cDTPA) and a C-linked derivative of DTPA (CT-DTPA) in athymic mice bearing human colon carcinoma xenografts. Significant differences in biodistribution were observed between 9N3 and cDTPA conjugates especially in the tumour uptake and blood, liver, femur and colon levels at 24, 48 and 144 h. Significantly higher tumour uptake was observed for 111In-cB72.3-9N3 compared with 111In-cB72.3-cDTPA at all time points. Radiolocalisation (RI) indices increased with time for the 9N3 conjugate but remained constant for the cDTPA conjugate. The biodistribution of 111In-labelled cB72.3-CT-DTPA was similar to that of 111In-labelled cB72.3-9N3 except for elevated kidney levels. A 12N4 macrocycle (a C-functionalised derivative of 1,4,7,10-tetraazacyclododecanetetraacetic acid) was also tested for its ability to chelate 111In and its biodistribution examined. Labelled conjugates with this macrocycle were more difficult to prepare in a stable form but gave a very similar biodistribution to the 9N3 macrocycle conjugate. Macrocycle-antibody conjugates of this type offer considerable promise for tumour imaging in patients. PMID:8018538

  7. Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis

    SciTech Connect

    Mountford, P.J.; Kettle, A.G.; O'Doherty, M.J.; Coakley, A.J. )

    1990-03-01

    Technetium-99m-HM-PAO (({sup 99m}Tc)HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr {sup 99m}Tc scan could replace the 24-hr {sup 111}In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr {sup 99}Tc-leukocyte scan, the 4-hr {sup 111}In-leukocyte scan, and the 24-hr {sup 111}In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr {sup 99m}Tc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr {sup 99m}Tc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr {sup 111}In-leukocyte scans. Because of the high incidence of false-positive 4-hr ({sup 99m}Tc)HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr {sup 111}In-leukocyte scans for detecting intraabdominal sepsis, and that serial {sup 99m}Tc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated.

  8. Pulmonary vascular sequestration of neutrophils in endotoxemia is initiated by an effect of endotoxin on the neutrophil in the rabbit

    SciTech Connect

    Haslett, C.; Worthen, G.S.; Giclas, P.C.; Morrison, D.C.; Henson, J.E.; Henson, P.M.

    1987-07-01

    Endotoxemia causes neutrophil sequestration in the pulmonary vascular bed. Such sequestration may be a critical initiating event in the generation of microvascular injury, although the mechanisms that lead to this localization are not understood. To investigate these phenomena, the following study employed intravenous pulses of /sup 111/Indium-tropolonate-labeled neutrophils (/sup 111/In-neutrophils), which circulated in the rabbit with normal kinetics and responded in a manner indistinguishable from unlabeled, circulating neutrophils in response to an intravenous injection of purified endotoxic lipopolysaccharide (LPS) or epinephrine. Pulmonary sequestration of /sup 111/In-neutrophils was assessed by quantitative external gamma camera scintigraphy of a lung suprahilar region of interest. Noninvasive assessment of radioactivity by this method accurately reflected total lung radioactivity, which was shown by autoradiography to be confined to the injected /sup 111/In-neutrophils. Intravenously administered LPS caused a marked, dose-dependent sequestration of /sup 111/In-neutrophils in the pulmonary vasculature, and exhaustive ultrastructural autoradiography showed discretely radiolabeled neutrophils located within pulmonary capillaries. A distinct effect was seen with an intravenous injection of as little as 100 ng per rabbit (i.e., 500 pg/ml blood). A 5-min ex vivo pretreatment of /sup 111/In-neutrophils with 10 ng to 10 micrograms/ml LPS in heat-inactivated plasma also caused dose-dependent pulmonary sequestration of the pretreated /sup 111/In-neutrophils but did not cause generalized neutropenia in recipient rabbits.

  9. Cardiac and vascular imaging with labeled platelets and leukocytes

    SciTech Connect

    Dewanjee, M.K.

    1984-07-01

    The contribution of platelets in atherosclerosis and thrombosis in animal models and in clinical studies has been quantified with 111In-platelet scintigraphy. New in vitro quantitative techniques have been developed using 111In-labeled platelets to determine the number of adherent platelets on deendothelialized surfaces of damaged vessel walls and synthetic vascular grafts. In vivo imaging techniques are semi-quantitative in nature; in these studies 111In radioactivity on thrombotic vessels or graft surfaces of iliac, femoral, or popliteal arteries is compared with contralateral vessels. Background 111In radioactivity in the circulating blood pool of venous and capillary networks and radioactivity in marrow decreases the sensitivity of these techniques. Subtraction of blood pool radioactivity with 99mTc-labeled autologous red cells and calculation of 111In radioactivity associated with platelet thrombus on vessel walls also have been performed for coronary, carotid, and femoral arteries. Although platelet concentrates are used frequently after open heart surgery (one to six per patient), consumption of platelets in the artificial lung or oxygenator, lysis of platelets during pumping, and suction of blood only recently have been quantified with the use of 111In-labeled platelets. These studies also demonstrated far less trauma to platelets with the use of a membrane rather than a bubble oxygenator. Further reduction in platelet consumption and trauma was observed with the use of prostacyclin, a short-acting drug with significant beneficial effect on platelet thrombus reduction and disaggregation of aggregated platelets. The role of polymorphonuclear leukocytes in inflammation, infection and myocardial infarction, and in vivo evaluation with 111In-leukocyte scintigraphy in animals and humans has been described.

  10. Life span and tissue distribution of 111indium-labeled blood platelets in hypomagnesemic lambs

    SciTech Connect

    Schneider, M.D.; Miller, J.K.; White, P.K.; Ramsey, N.

    1983-05-01

    Circulating platelets may be activated by exposed triple-helical collagen in atherosclerotic lesions in Mg-deficient ruminants. Autologous platelets, labeled in vitro with 111In and determined to be active, were injected into 5 hypomagnesemic and 3 control lambs fed semipurified diets with 100 or 2,000 mg of Mg/kg of feed for 3 months. During the first 68 hours, 111In concentrations were 11 times higher in packed cells than in plasma. Packed-cell 111In increased 60% during the first 2 hours, probably due to initial tissue sequestration and later release of labeled platelets. Thereafter, platelet half-life span averaged 60 and 63 hours for hypomagnesemic and control lambs. After 68 hours, lambs were injected with native vascular collagen fibrils at 500 micrograms/kg of body weight to initiate reversible platelet aggregation. Within 1 minute, 83% of packed-cell 111In disappeared from circulation. Thirty minutes later, the lambs were euthanatized and necropsied and in the lungs, liver, and spleen, 111In averaged 24%, 19%, and 9%, respectively, of 111In injected 68 hours earlier. Organ deposits were not affected by Mg intake, but 111In in the lungs was somewhat lower in 2 lambs injected with inactivated collagen. Pathologic changes induced by reversible platelet aggregation were compatible with right ventricular failure complicated by pulmonary edema, similar to changes in hypomagnesemic lambs that died spontaneously. Platelets in blood exposed to vascular lesions in hypomagnesemic ruminants could be a major mortality risk factor in grass tetany disease.

  11. Detection of osteomyelitis at fracture nonunion sites: comparison of two scintigraphic methods

    SciTech Connect

    Seabold, J.E.; Nepola, J.V.; Conrad, G.R.; Marsh, J.L.; Montgomery, W.J.; Bricker, J.A.; Kirchner, P.T.

    1989-05-01

    Forty-nine patients with 50 fracture nonunions 4-48 months after injury underwent technetium-99m methylene diphosphonate (99mTc-MDP) scintigraphy on day 1, combined 99mTc-MDP and indium-111 leukocyte (111In-WBC) scintigraphy on day 2, and gallium-67 (67Ga) scintigraphy on day 3. The results were compared to evaluate the relative abilities of these scintigraphic techniques to detect osteomyelitis. Combined 99mTc-MDP/111In-WBC images were interpreted with the use of two criteria. A positive study by the first criterion required 111In-WBC localization in the region of the nonunion fracture. A positive study by the second criterion required 111In-WBC localization in bone at the fracture site. The first criterion yielded a sensitivity of 84%, specificity of 72%, and accuracy of 74%; the specificity improved to 97% with an accuracy of 88% when the second criterion was used. Ten (25%) of the 40 patients thought not to have osteomyelitis by clinical criteria at the time of imaging had true-positive 99mTc-MDP/111In-WBC studies by biopsy culture results. Gallium-67 studies were interpreted as nondiagnostic if localization of radioisotope at fracture sites was equal to that with 99mTc-MDP, positive if 67Ga localization was greater than that of 99mTc-MDP, and negative if it was less than that of 99mTc-MDP. Twenty-one 67Ga studies were interpreted as nondiagnostic; 11 (52%) of the 21 had culture-positive fracture sites. The accuracy of 67Ga/99mTc-MDP imaging was 39%. Combined 99mTc-MDP/111In-WBC imaging is useful in the detection of osteomyelitis at fracture nonunion sites and improves the specificity of 111In-WBC imaging by differentiating inflammation/infection in adjacent soft tissue from osteomyelitis at the fracture site.

  12. sup 111 Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

    SciTech Connect

    Haslett, C.; Shen, A.S.; Feldsien, D.C.; Allen, D.; Henson, P.M.; Cherniack, R.M. )

    1989-09-01

    Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.

  13. The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma

    PubMed Central

    Iyer, Arun K.; Su, Yang; Feng, Jinjin; Lan, Xiaoli; Zhu, Xiaodong; Liu, Yue; Gao, Dongwei; Seo, Youngho; VanBrocklin, Henry F.; Broaddus, V. Courtney; Liu, Bin; He, Jiang

    2011-01-01

    Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with 111In (111In-IL-M1), along with control non-targeted liposomes (111In-CL). Incubation of 111In-IL-M1 with M28, VAMT-1, and a control non-tumorigenic cell-line (BPH-1) at 37°C for 24 h revealed efficient binding and rapid internalization of ILs into both subtypes of tumor cells but not into the BPH-1 cells; internalization accounted for approximately 81-94% of total cell accumulation in mesothelioma cells compared to 37-55% in control cells. In tumor bearing mice intravenous (i.v.) injection of 111In-IL-M1 led to remarkable tumor accumulation: 4 % and 4.7% injected dose per gram (% ID/g) for M28 and VAMT-1 tumors, respectively, 48 h after injection. Furthermore, tumor uptake of 111In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of 111In-CL in tumor-bearing mice revealed very low uptake in both subtypes of mesothelioma, 48 h after injection. In conclusion, M1 scFv-anchored ILs showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid subtypes of human mesothelioma, demonstrating its potential as a promising vector for enhanced tumor drug targeting. PMID:21255833

  14. Relationship Between Chromatin Structure and Sensitivity to Molecularly Targeted Auger Electron Radiation Therapy

    SciTech Connect

    Terry, Samantha Y.A.

    2012-07-15

    Purpose: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. Methods and Materials: Chromatin structure was altered in MDA-MB-468 and 231-H2N human breast cancer cells by suberoylanilide hydroxamic acid (SAHA), 5-aza-2-deoxycytidine, or hypertonic treatment. The extent and duration of chromatin structural changes were evaluated using the micrococcal nuclease assay. DNA damage ({gamma}H2AX assay) and clonogenic survival were evaluated after exposure to {sup 111}In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, or IR. The intracellular distribution of {sup 111}In-DTPA-hEGF after chromatin modification was investigated in cell fractionation experiments. Results: Chromatin remained condensed for up to 20 minutes after NaCl and in a relaxed state 24 hours after SAHA treatment. The number of {gamma}H2AX foci per cell was greater in MDA-MB-468 and 231-H2N cells after IR (0.5 Gy) plus SAHA (1 {mu}M) compared with IR alone (16 {+-} 0.6 and 14 {+-} 0.3 vs. 12 {+-} 0.4 and 11 {+-} 0.2, respectively). More {gamma}H2AX foci were observed in MDA-MB-468 and 231-H2N cells exposed to {sup 111}In-DTPA-hEGF (6 MBq/{mu}g) plus SAHA vs. {sup 111}In-DTPA-hEGF alone (11 {+-} 0.3 and 12 {+-} 0.7 vs. 9 {+-} 0.4 and 7 {+-} 0.3, respectively). 5-aza-2-deoxycytidine enhanced the DNA damage caused by IR and {sup 111}In-DTPA-hEGF. Clonogenic survival was reduced in MDA-MB-468 and 231-H2N cells after IR (6 Gy) plus SAHA (1 {mu}M) vs. IR alone (0.6% {+-} 0.01 and 0.3% {+-} 0.2 vs. 5.8% {+-} 0.2 and 2% {+-} 0.1, respectively) and after {sup 111}In-DTPA-hEGF plus SAHA compared to {sup 111}In-DTPA-hEGF alone (21% {+-} 0.4% and 19% {+-} 4.6 vs. 33% {+-} 2.3 and 32% {+-} 3.7). SAHA did not affect {sup 111}In-DTPA-hEGF nuclear localization. Hypertonic treatment resulted in fewer {gamma}H2AX foci per cell

  15. Activated Platelets in Carotid Artery Thrombosis in Mice Can Be Selectively Targeted with a Radiolabeled Single-Chain Antibody

    PubMed Central

    Goldschmidt, Jürgen; Pethe, Annette; Hagemeyer, Christoph E.; Neudorfer, Irene; Zirlik, Andreas; Weber, Wolfgang A.; Bode, Christoph; Meyer, Philipp T.

    2011-01-01

    Background Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. Methodology/Principal Findings LIBS as well as an unspecific control single-chain antibody were labeled with 111Indium (111In) via bifunctional DTPA ( = 111In-LIBS/111In-control). Autoradiography after incubation with 111In-LIBS on activated platelets in vitro (mean 3866±28 DLU/mm2, 4010±630 DLU/mm2 and 4520±293 DLU/mm2) produced a significantly higher ligand uptake compared to 111In-control (2101±76 DLU/mm2, 1181±96 DLU/mm2 and 1866±246 DLU/mm2) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of 111In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630±10650 DLU/mm2 vs. 17390±7470 DLU/mm2; P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with 111In-LIBS resulted in a significant increase of the target-to-background ratio compared to 111In-control (1.99±0.36 vs. 1.1±0.24; P<0.01). Conclusions/Significance Nuclear imaging with 111In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis

  16. Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

    SciTech Connect

    Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

    1983-04-01

    We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs.

  17. Localization and visualization of pulmonary emboli with radiolabeled fibrin-specific monoclonal antibody

    SciTech Connect

    Kanke, M.; Matsueda, G.R.; Strauss, H.W.; Yasuda, T.; Liau, C.S.; Khaw, B.A. )

    1991-06-01

    Indium-111-labeled monoclonal antibody 64C5 specific for the beta-chain of fibrin monomer was used to image canine (n = 6) experimental pulmonary emboli (at least one barium-thrombin and one copper-coil induced clot per dog). Uptake of {sup 111}In-64C5 and 125I-control-DIG26-11 were compared in 10 clots (7 barium-thrombin and 3 copper-coil) identified in the lungs. There was no difference in the blood clearance of {sup 111}In-64C5 and 125I-DIG26-11. Uptake of {sup 111}In-64C5 (0.183 {plus minus} 0.105, mean %ID/g) was greater than 125I-DIG26-11 (0.024 {plus minus} 0.025) in pulmonary clots (p less than 0.001). Mean thrombus to blood ratios at 24 hr were 6.78:1 for 64C5 and 0.57:1 for DIG26-11. The clots visualized in vivo were larger (0.315 {plus minus} 0.381 g) than clots not visualized (0.089 {plus minus} 0.098). Negative images were recorded in three dogs with pulmonary emboli, injected with {sup 111}In-labeled control monoclonal antibody 3H3. These data suggest that {sup 111}In-labeled antifibrin can detect large pulmonary emboli in vivo.

  18. Distribution of radiolabeled human and mouse monoclonal IgM antibodies in murine models

    SciTech Connect

    Halpern, S.E.; Hagan, P.L.; Chen, A.; Birdwell, C.R.; Bartholomew, R.M.; Burnett, K.G.; David, G.S.; Poggenburg, K.; Merchant, B.; Carlo, D.J.

    1988-10-01

    The distribution and kinetics of six human and one murine monoclonal IgM antibodies (MoAb) were studied in BALB/c mice. Labeling was with /sup 111/In, /sup 75/Se, and /sup 125/I. The monomers and pentamers of certain MoAbs were studied. Human distribution studies were also performed. The serum containing (/sup 111/In)MoAb was obtained from one of the patients 24 hr after administration and injected into mice which were then killed and assayed for /sup 111/In distribution. In general, the (/sup 75/Se) and (/sup 111/In)MoAbs had distribution and kinetic patterns that were similar while the /sup 125/I-labeled MoAbs dehalogenated after 4 hr. Monomers and pentamers had highly similar distributions suggesting that the distribution of IgMs may be based on factors other than molecular size. The murine IgM showed a somewhat different distribution in mice than did human IgMs. Serum from the patient containing (/sup 111/In)MoAb had a distribution in mice similar to that of the patient with high liver and gastrointestinal uptake. The human imaging indicates that it is possible to target tumor with human IgM MoAbs, but significant problems remain in regard to their clinical use.

  19. Biotinylated polyacrylamide-based metal-chelating polymers and their influence on antigen recognition following conjugation to a trastuzumab Fab fragment.

    PubMed

    Liu, Peng; Boyle, Amanda J; Lu, Yijie; Reilly, Raymond M; Winnik, Mitchell A

    2012-09-10

    We report the synthesis and characterization of metal-chelating polymers (MCPs) with a terminal biotin and a polyacrylamide backbone harboring multiple diethylenetriaminepentaacetic acid (DTPA) chelating sites. These polymers are conjugated to a streptavidin (SAv)-modified Fab fragment of trastuzumab (tmFab) and subsequently complexed with (111)In through DTPA. Trastuzumab has specific targeting ability toward human epidermal growth factor receptor-2 (HER2), which is overexpressed on some types of breast cancer cells and ovarian cancer cells. (111)In can generate Auger electrons which cause lethal DNA double strand breaks. The radioimmunoconjugates (RICs) were designed to target HER2 overexpressing cancer cells and carry multiple copies of (111)In to these cells. The mole maximum specific activities of these polymers were investigated by loading the polymers with (111)In at an increasing (111)In to polymer ratio. The polymers show 55-fold to 138-fold higher maximum specific activity than DTPA modified tmFab-SAv. Moreover, the HER2 immunoreactivities of these RICs were evaluated by measuring their specific binding ability toward HER2 overexpressing SKOV-3 ovarian cancer cells. The results demonstrate that although in the presence of polymer there is increased nonspecific binding, HER2 targeting ability was retained, ensuring the radionuclide delivery ability of these RICs. PMID:22871127

  20. Specificity of indium-111 granulocyte scanning and fecal excretion measurement in inflammatory bowel disease--an autoradiographic study

    SciTech Connect

    Keshavarzian, A.; Price, Y.E.; Peters, A.M.; Lavender, J.P.; Wright, N.A.; Hodgson, H.J.

    1985-12-01

    The validity of /sup 111/In granulocyte scanning and fecal excretion measurement, as a reflection of loss of cells into the gastrointestinal tract, was studied using an autoradiographic technique in 11 patients in whom /sup 111/In granulocyte scan and colonoscopy were carried out simultaneously. /sup 111/In granulocytes were injected 1.5-4 hr prior to colonoscopy, and intraluminal fluid, mucosal brushings, and colonic biopsies were collected during the colonoscopy. In two patients with no histological evidence of inflammatory bowel disease, and four patients with clinically and histologically inactive inflammatory bowel disease, no /sup 111/Indium was detected in fluid, brushing, or biopsies. In five patients with active disease, 85% of the /sup 111/In activity in colonic fluid was precipitated by low-speed centrifugation. Autoradiography confirmed that the label remained attached to whole granulocytes in colonic fluid and mucosal brushings. Studies on biopsies, at intervals up to 4 1/2 hr following labeled granulocyte injection, demonstrated labeled polymorphonuclear neutrophils (PMNs) on the inflamed epithelial surface, with occasional cells in crypt abscesses by 110 min. We conclude that the techniques of /sup 111/In granulocyte scanning and fecal counting in patients with IBD are specifically measuring cell loss; labeled PMNs are capable of migrating through the gastrointestinal mucosa, in active disease, within 2 hr of administration.

  1. Relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled monoclonal antibodies

    SciTech Connect

    Sakahara, H.; Endo, K.; Koizumi, M.; Nakashima, T.; Kunimatsu, M.; Watanabe, Y.; Kawamura, Y.; Nakamura, T.; Tanaka, H.; Kotoura, Y.

    1988-02-01

    The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using /sup 125/I- and /sup 111/In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies--OST6, OST7, and OST15--raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both /sup 125/I- and /sup 111/In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, /sup 125/I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than /sup 125/I-labeled OST7. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of /sup 111/In-labeled OST6 was higher, although not significantly, than that of /sup 111/In-labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either /sup 125/I or /sup 111/In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding.

  2. Comparison of indium-111 nonspecific polyclonal IgG with indium-111-leukocytes in a canine osteomyelitis model

    SciTech Connect

    Schauwecker, D.S.; Carlson, K.A.; Miller, G.A.; Kalasinski, L.A.; Katz, B.P. )

    1991-07-01

    Osteomyelitis was surgically produced in the proximal tibia of ten dogs. A sham operation was performed on the other tibia. Early (3 hr) and late (20 hr) imaging was performed 1, 4, 7, 10, and 13 wk later, while the osteomyelitis progressed from acute to chronic. Indium-111-IgG had a significantly greater accumulation at the osteomyelitis site than 111In-leukocytes, both during early (p = 0.001) and late (p = 0.03) imaging, and at each of the weeks studied (p less than 0.001). During early imaging, both agents gave equivalent lesion to background ratios. On the late images, the 111In-leukocytes gave significantly higher lesion-to-background ratios than 111In-IgG (p less than 0.001) and higher ratios than they did during the early images (p less than 0.001). Both agents had greater accumulation in acute osteomyelitis than in chronic osteomyelitis (p less than 0.02). Osteomyelitis in the surgical site can be distinguished from the uptake in the sham surgery site using 111In-leukocytes, but not when using 111In-IgG.

  3. Indium-111-granulocyte scintigraphy in brain abscess diagnosis: Limitations and pitfalls

    SciTech Connect

    Schmidt, K.G.; Rasmussen, J.W.; Frederiksen, P.B.; Kock-Jensen, C.; Pedersen, N.T. )

    1990-07-01

    The scintigrams and records of 28 patients referred for indium-111-granulocyte scintigraphy (111In-GS) because of a suspected brain abscess were studied retrospectively. The final diagnosis was brain abscess in 8 patients, brain tumor in 18 patients, and infarct and hematoma in 1 patient each. Five patients not on corticosteroid treatment showed intense focal 111In accumulation in abscesses, whereas an abscess patient receiving a high steroid dose showed no uptake. Two patients studied twice showed intense uptake in abscesses when not on steroid therapy or on a low dose, whereas no uptake was seen when they received high or medium doses. Weak or moderate 111In uptake was observed in nine tumors. Microscopically assessed degree of tumor granulocyte infiltration, vessel proliferation, and hemorrhage did not correlate with the outcome of 111In GS. Our results suggest that intense focal cerebral 111In uptake favors the abscess diagnosis. Abscesses may go undetected, however, in patients on high- or medium-dose steroid therapy.

  4. Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.

    PubMed

    Howard, Scott C; Trifilio, Steven; Gregory, Tara K; Baxter, Nadine; McBride, Ali

    2016-03-01

    Effective new treatments are now available for patients with hematologic malignancies. However, their propensity to cause tumor lysis syndrome (TLS) has not been systematically examined. A literature search identified published Phase I-III clinical trials of monoclonal antibodies (otlertuzumab, brentuximab, obinutuzumab, ibritumomab, ofatumumab); tyrosine kinase inhibitors (alvocidib [flavopiridol], dinaciclib, ibrutinib, nilotinib, dasatinib, idelalisib, venetoclax [ABT-199]); proteasome inhibitors (oprozomib, carfilzomib); chimeric antigen receptor (CAR) T cells; and the proapoptotic agent lenalidomide. Abstracts from major congresses were also reviewed. Idelalisib and ofatumumab had no reported TLS. TLS incidence was ≤5 % with brentuximab vedotin (for anaplastic large-cell lymphoma), carfilzomib and lenalidomide (for multiple myeloma), dasatinib (for acute lymphoblastic leukemia), and oprozomib (for various hematologic malignancies). TLS incidences were 8.3 and 8.9 % in two trials of venetoclax (for chronic lymphocytic leukemia [CLL]) and 10 % in trials of CAR T cells (for B-cell malignancies) and obinutuzumab (for non-Hodgkin lymphoma). TLS rates of 15 % with dinaciclib and 42 and 53 % with alvocidib (with sequential cytarabine and mitoxantrone) were seen in trials of acute leukemias. TLS mitigation was employed routinely in clinical trials of alvocidib and lenalidomide. However, TLS mitigation strategies were not mentioned or stated only in general terms for many studies of other agents. The risk of TLS persists in the current era of novel and targeted therapy for hematologic malignancies and was seen to some extent with most agents. Our findings underscore the importance of continued awareness, risk assessment, and prevention to reduce this serious potential complication of effective anticancer therapy. PMID:26758269

  5. Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel approach to radionuclide therapy.

    PubMed

    Panigone, S; Nunn, A D

    2006-12-01

    Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides. PMID:17043628

  6. Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia

    SciTech Connect

    Kochanek, P.M.; Dutka, A.J.; Kumaroo, K.K.; Hallenbech, J.M.

    1987-12-14

    The authors treated four anesthetized dogs with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous /sup 111/In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone administered 5 min prior to ischemia and continuously throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude when compared to controls. They estimated platelet accumulation as /sup 111/In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered /sup 111/In labeled platelet accumulation when compared to controls. Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved. 20 references, 1 figure.

  7. Atomic-level observation of Ag-ion hopping motion in AgI

    NASA Astrophysics Data System (ADS)

    Sato, W.; Komatsuda, S.; Mizuuchi, R.; Irioka, N.; Kawata, S.; Ohkubo, Y.

    2015-04-01

    Applicability of the 111mCd(→111Cd) and 111In(→111Cd) probes to the study of dynamics in polycrystalline silver iodide (AgI) was examined by means of the time-differential perturbed angular correlation technique. It was found that the 111mCd(→111Cd) probe occupies a unique site in γ-AgI and exhibits nuclear relaxation caused by dynamic perturbation arising from Ag + hopping motion in α-AgI; while the residential sites of 111In(→111Cd) vary, suggesting that 111In ions can not settle themselves in a fixed site in the AgI crystal structure. We here demonstrate that 111mCd(→111Cd) can be a potential nucleus to probe the Ag +-ion dynamic motion in α-AgI.

  8. In vivo dissolution measurement with indium-111 summation peak ratios

    SciTech Connect

    Jay, M.; Woodward, M.A.; Brouwer, K.R.

    1985-10-01

    Dissolution of (/sup 111/In)labeled tablets was measured in vivo in a totally noninvasive manner by using a modification of the perturbed angular correlation technique known as the summation peak ratio method. This method, which requires the incorporation of only 10-12 microCi into the dosage form, provided reliable dissolution data after oral administration of (/sup 111/In)lactose tablets. These results were supported by in vitro experiments which demonstrated that the dissolution rate as measured by the summation peak ratio method was in close agreement with the dissolution rate of salicylic acid in a (/sup 111/In)salicylic acid tablet. The method has the advantages of using only one detector, thereby avoiding the need for complex coincidence counting systems, requiring less radioactivity, and being potentially applicable to a gamma camera imaging system.

  9. Imaging of inflammatory processes with labeled cells

    SciTech Connect

    Froelich, J.W.; Swanson, D.

    1984-04-01

    Radionuclide techniques for localizing inflammatory processes had relied heavily upon /sup 67/Ga-citrate until McAfee and Thakur described the technique for the radiolabeling of leukocytes with /sup 111/In-oxine. Since their initial description in 1976 there has been continued development of the radiopharmaceutical, as well as clinical efficacy. At present /sup 111/In-labeled leukocytes continue to be handled as an investigational new drug but this has not greatly limited its clinical availability. Indium-/sup 111/ leukocytes are the agent of choice for evaluation of patients with fever of unknown origin, osteomyelitis, and prosthetic graft infections; and preliminary data shows great promise in the area of detecting reoccurrence of inflammatory bowel disease. This article attempts to review currently accepted uses of 111In leukocytes as well as potential areas of application.

  10. Molecular Design of Bisphosphonate-Modified Proteins for Efficient Bone Targeting In Vivo

    PubMed Central

    Katsumi, Hidemasa; Sano, Jun-ichi; Nishikawa, Makiya; Hanzawa, Keiko; Sakane, Toshiyasu; Yamamoto, Akira

    2015-01-01

    To establish a rational molecular design for bisphosphonate (BP)-modified proteins for efficient bone targeting, a pharmacokinetic study was performed using a series of alendronate (ALN), a nitrogen-containing BP, modified proteins with various molecular weights and varying degrees of modification. Four proteins with different molecular weight—yeast glutathione reductase (GR; MW: 112,000 Da), bovine serum albumin (BSA; MW: 67,000 Da), recombinant human superoxide dismutase (SOD; MW: 32,000 Da), and chicken egg white lysozyme (LZM; MW: 14,000 Da)—were modified with ALN to obtain ALN-modified proteins. Pharmacokinetic analysis of the tissue distribution of the ALN-modified and unmodified proteins was performed after radiolabeling them with indium-111 (111In) by using a bifunctional chelating agent. Calculation of tissue uptake clearances revealed that the bone uptake clearances of 111In-ALN-modified proteins were proportional to the degree of ALN modification. 111In-GR-ALN and BSA-ALN, the two high-molecular-weight proteins, efficiently accumulated in bones, regardless of the degree of ALN modification. Approximately 36 and 34% of the dose, respectively, was calculated to be delivered to the bones. In contrast, the maximum amounts taken up by bone were 18 and 13% of the dose for 111In-SOD-ALN(32) and LZM-ALN(9), respectively, because of their high renal clearance. 111In-SOD modified with both polyethylene glycol (PEG) and ALN (111In-PEG-SOD-ALN) was efficiently delivered to the bone. Approximately 36% of the dose was estimated to be delivered to the bones. In an experimental bone metastasis mouse model, treatment with PEG-SOD-ALN significantly reduced the number of tumor cells in the bone of the mice. These results indicate that the combination of PEG and ALN modification is a promising approach for efficient bone targeting of proteins with a high total-body clearance. PMID:26287482

  11. Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts.

    PubMed

    Gerber, David E; Hao, Guiyang; Watkins, Linda; Stafford, Jason H; Anderson, Jon; Holbein, Blair; Öz, Orhan K; Mathews, Dana; Thorpe, Philip E; Hassan, Gedaa; Kumar, Amit; Brekken, Rolf A; Sun, Xiankai

    2015-01-01

    Bavituximab is a chimeric monoclonal antibody with immune modulating and tumor-associated vascular disrupting properties demonstrated in models of non-small cell lung cancer (NSCLC). The molecular target of Bavituximab, phosphatidylserine (PS), is exposed on the outer leaflet of the membrane bi-layer of malignant vascular endothelial cells and tumor cells to a greater extent than on normal tissues. We evaluated the tumor-targeting properties of Bavituximab for imaging of NSCLC xenografts when radiolabeled with (111)In through conjugation with a bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). In vitro binding of (111)In-DOTA-Bavituximab to PS was determined by enzyme-linked immunosorbent assay (ELISA). Biodistribution of (111)In-DOTA-Bavituximab was conducted in normal rats, which provided data for dosimetry calculation. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed in athymic nude rats bearing A549 NSCLC xenografts. At the molar conjugation ratio of 0.54 DOTA per Bavituximab, the PS binding affinity of (111)In-DOTA-Bavituximab was comparable to that of unmodified Bavituximab. Based on the quantitative SPECT/CT imaging data analysis, (111)In-DOTA-Bavituximab demonstrated tumor-specific uptake as measured by the tumor-tomuscle ratio, which peaked at 5.2 at 72 hr post-injection. In contrast, the control antibody only presented a contrast of 1.2 at the same time point.These findings may underlie the diagnostic efficacy and relative low rates of systemic vascular and immune-related toxicities of this immunoconjugate. Future applications of (111)In-DOTA-bavituximab may include prediction of efficacy, indication of tumor immunologic status, or characterization of radiographic findings. PMID:26550540

  12. Comparison of gallium-67 versus indium-111 monoclonal antibody (96. 5, ZME-018) in detection of human melanoma in athymic mice

    SciTech Connect

    Chan, S.M.; Hoffer, P.B.; Maric, N.; Zoghbi, S.S.; Kirkwood, J.M.; Ernstoff, M.S.; Duray, P.H.; Gerich, B.

    1987-09-01

    We compared the biodistribution of two radiolabeled, whole, tumor selective monoclonal antibodies (( /sup 111/In)96.5, (/sup 111/In)ZME-018) to /sup 67/Ga in nude mice bearing a human melanoma known to express p97 antigen. Localization of gallium was determined 48 hr following i.v. injection. Localization of the radiolabeled antibodies was determined at 3 days and 7 days following i.v. injection. All agents showed more or less similar absolute tumor uptake which varied between 22% and 36% of the injected dose per gram of tumor. Only the tumor uptake of (/sup 111/In)96.5 antibody at 7 days was significantly lower than the /sup 67/Ga uptake at 48 hr. However, uptake in normal tissues was generally higher for both antibodies at 3 and 7 days than for /sup 67/Ga uptake at 48 hr. Therefore, the tumor-to-blood ratio for /sup 67/Ga was tenfold higher than that for either antibody, the tumor-to-muscle ratio was twofold higher. Bone was the only organ in which the tumor-to-organ ratio was consistently higher with radiolabeled antibody than with /sup 67/Ga. The tumor-to-liver and tumor-to-intestine ratios were comparable. Localization of the two tumor selective antibodies was greater than a nonspecific control antibody (( /sup 111/In)CEA) and change in specific activity from 0.17 mCi/mg to 3.3 mCi/mg did not influence localization. From these animal data it may be anticipated that tumor imaging with (/sup 111/In)96.5 or (/sup 111/In)ZME-018 will not be superior to imaging with 67Ga for detection of melanoma.

  13. Indium-111-labeled autologous leukocyte imaging and fecal excretion. Comparison with conventional methods of assessment of inflammatory bowel disease

    SciTech Connect

    Leddin, D.J.; Paterson, W.G.; DaCosta, L.R.; Dinda, P.K.; Depew, W.T.; Markotich, J.; McKaigney, J.P.; Groll, A.; Beck, I.T.

    1987-04-01

    This study was designed to evaluate the role of /sup 111/In-labeled leukocyte imaging and fecal excretion in the assessment of inflammatory bowel disease. We compared these tests to various indices of disease activity in Crohn's disease, to Truelove's grading in ulcerative colitis, and to endoscopy, x-ray, and pathology in both diseases. Eleven controls, 16 patients with Crohn's disease, 13 with ulcerative colitis, and 3 with other types of acute bowel inflammation were studied (positive controls). Indium scanning was performed at 1, 4, and 24 hr. Fourteen of 16 patients with active Crohn's disease had positive scans but in only five was localization accurate. One patient had inactive ulcerative colitis, and the scan was negative. Of 12 patients with active ulcerative colitis, 10 had positive scans but disease localization was accurate in only four. Disease extent was correctly defined in 1 of the 3 Positive Controls. There was no significant difference in the accuracy of scanning at 1, 4, or 24 hr. /sup 111/In fecal excretion was significantly higher in patients with inflammatory bowel disease than in controls, and there was correlation between /sup 111/In fecal excretion and most of the indices of disease activity in Crohn's disease. In ulcerative colitis, /sup 111/In fecal excretion did not correlate with Truelove's grading but reflected colonoscopic assessment of severity. In conclusion, /sup 111/In-labeled leukocyte scanning lacks sensitivity with respect to disease extent, but fecal excretion of /sup 111/In correlates well with disease severity as determined by other methods.

  14. Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts

    PubMed Central

    Gerber, David E; Hao, Guiyang; Watkins, Linda; Stafford, Jason H; Anderson, Jon; Holbein, Blair; Öz, Orhan K; Mathews, Dana; Thorpe, Philip E; Hassan, Gedaa; Kumar, Amit; Brekken, Rolf A; Sun, Xiankai

    2015-01-01

    Bavituximab is a chimeric monoclonal antibody with immune modulating and tumor-associated vascular disrupting properties demonstrated in models of non-small cell lung cancer (NSCLC). The molecular target of Bavituximab, phosphatidylserine (PS), is exposed on the outer leaflet of the membrane bi-layer of malignant vascular endothelial cells and tumor cells to a greater extent than on normal tissues. We evaluated the tumor-targeting properties of Bavituximab for imaging of NSCLC xenografts when radiolabeled with 111In through conjugation with a bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). In vitro binding of 111In-DOTA-Bavituximab to PS was determined by enzyme-linked immunosorbent assay (ELISA). Biodistribution of 111In-DOTA-Bavituximab was conducted in normal rats, which provided data for dosimetry calculation. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed in athymic nude rats bearing A549 NSCLC xenografts. At the molar conjugation ratio of 0.54 DOTA per Bavituximab, the PS binding affinity of 111In-DOTA-Bavituximab was comparable to that of unmodified Bavituximab. Based on the quantitative SPECT/CT imaging data analysis, 111In-DOTA-Bavituximab demonstrated tumor-specific uptake as measured by the tumor-tomuscle ratio, which peaked at 5.2 at 72 hr post-injection. In contrast, the control antibody only presented a contrast of 1.2 at the same time point.These findings may underlie the diagnostic efficacy and relative low rates of systemic vascular and immune-related toxicities of this immunoconjugate. Future applications of 111In-DOTA-bavituximab may include prediction of efficacy, indication of tumor immunologic status, or characterization of radiographic findings. PMID:26550540

  15. Use of a ray-based reconstruction algorithm to accurately quantify preclinical microSPECT images.

    PubMed

    Vandeghinste, Bert; Van Holen, Roel; Vanhove, Christian; De Vos, Filip; Vandenberghe, Stefaan; Staelens, Steven

    2014-01-01

    This work aimed to measure the in vivo quantification errors obtained when ray-based iterative reconstruction is used in micro-single-photon emission computed tomography (SPECT). This was investigated with an extensive phantom-based evaluation and two typical in vivo studies using 99mTc and 111In, measured on a commercially available cadmium zinc telluride (CZT)-based small-animal scanner. Iterative reconstruction was implemented on the GPU using ray tracing, including (1) scatter correction, (2) computed tomography-based attenuation correction, (3) resolution recovery, and (4) edge-preserving smoothing. It was validated using a National Electrical Manufacturers Association (NEMA) phantom. The in vivo quantification error was determined for two radiotracers: [99mTc]DMSA in naive mice (n  =  10 kidneys) and [111In]octreotide in mice (n  =  6) inoculated with a xenograft neuroendocrine tumor (NCI-H727). The measured energy resolution is 5.3% for 140.51 keV (99mTc), 4.8% for 171.30 keV, and 3.3% for 245.39 keV (111In). For 99mTc, an uncorrected quantification error of 28 ± 3% is reduced to 8 ± 3%. For 111In, the error reduces from 26 ± 14% to 6 ± 22%. The in vivo error obtained with 99mTc-dimercaptosuccinic acid ([99mTc]DMSA) is reduced from 16.2 ± 2.8% to -0.3 ± 2.1% and from 16.7 ± 10.1% to 2.2 ± 10.6% with [111In]octreotide. Absolute quantitative in vivo SPECT is possible without explicit system matrix measurements. An absolute in vivo quantification error smaller than 5% was achieved and exemplified for both [99mTc]DMSA and [111In]octreotide. PMID:24824961

  16. Improvement of biodistribution and therapeutic index via increase of polyethylene glycol on drug-carrying liposomes in an HT-29/luc xenografted mouse model.

    PubMed

    Chow, Tong-Hsien; Lin, Yi-Yu; Hwang, Jeng-Jong; Wang, Hsin-Ell; Tseng, Yun-Long; Wang, Shyh-Jen; Liu, Ren-Shyan; Lin, Wuu-Jyh; Yang, Chung-Shi; Ting, Gann

    2009-06-01

    Liposomes modified with a high concentration of polyethylene glycol (PEG) could significantly prolong the retention time of the carried drug in the circulation, thus improving the drug accumulation in the tumor. In this study, 6 mol% rather than 0.9 mol% PEGylated liposomes (100 nm in diameter) encapsulated with indium-111 were used in a human colorectal carcinoma HT-29/luc tumor-bearing mouse model for comparing the PEGylation effect. Pharmacokinetics, biodistribution, passive-targeted assay, bioluminescence imaging (BLI) and tumor growth measurements were used for the spatial and temporal distribution, tumor localization and therapeutic evaluation of the drug. Pharmacokinetic studies indicated that the terminal half-life (T((1/2))lambdaz) and C(max) of 6 mol% PEG (111)In liposomes were similar to those of 0.9 mol% PEG (111)In liposomes. In the blood, the total body clearance (Cl) of 6 mol% PEG (111)In liposomes was about 1.7-fold lower and the area under the curve (AUC) was 1.7-fold higher than those of 0.9 mol% PEG (111)In liposomes. These results showed that the long-term circulation and localization of 6 mol% PEGylated liposomes was more appropriate for use in the tumor-bearing animal model. In addition, the biodistribution of 6 mol% PEG (111)In liposomes showed significantly lower uptake in the liver, spleen, kidneys, small intestine and bone marrow than those of 0.9 mol% PEG (111)In liposomes. The clearance rate of both drugs from the blood decreased with time, with the maximum at 24 h post intravenous (i.v.) injection. Prominent tumor uptake and the highest tumor/muscle ratios were found at 48 h post injection. Both AUC and relative ratio of the AUCs (RR-AUC) also showed that 6 mol% PEGylated liposomes significantly reduced the uptake of drugs in the reticuloendothelial system (RES), yet enhanced the uptake in the tumor. Gamma scintigraphy at 48 h post injection also demonstrated more distinct tumor uptake with 6 mol% PEG (111)In liposomes as compared to

  17. Compatibility tests of materials for a lithium-cooled space power reactor concept

    NASA Technical Reports Server (NTRS)

    Sinclair, J. H.

    1973-01-01

    Materials for a lithium-cooled space power reactor concept must be chemically compatible for up to 50,000 hr at high temperature. Capsule tests at 1040 C (1900 F) were made of material combinations of prime interest: T-111 in direct contact with uranium mononitride (UN), Un in vacuum separated from T-111 by tungsten wire, UN with various oxygen impurity levels enclosed in tungsten wire lithium-filled T-111 capsules, and TZM and lithium together in T-111 capsules. All combinations were compatible for over 2800 hr except for T-111 in direct contact with UN.

  18. Preparation and immunoreactivity of high specific activity indium-111-DTPA labeled monoclonal antibody (MoAb) using ultrapure indium-111

    SciTech Connect

    Zoghbi, S.S.; Neumann, R.D.; Gottschalk, A.

    1986-10-01

    The preparation of high-specific activity /sup 111/In-DTPA-MoAb without increasing the number of DTPA molecules per Ab was investigated. Instant thin layer chromatography was used to assay the relationship between labeling efficiencies and specific activities. With ultrapurified /sup 111/In, the specific activity of the radiolabeled MoAb approached the expected theoretic maximum of 100 muCi/microgram. The bioactivity of such high-specific activity preparation showed no degradation as measured by in vitro cell binding assay.

  19. Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors

    PubMed Central

    Honarvar, Hadis; Westerlund, Kristina; Altai, Mohamed; Sandström, Mattias; Orlova, Anna; Tolmachev, Vladimir; Karlström, Amelie Eriksson

    2016-01-01

    Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera ZHER2:342-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both 125I and 111In. 111In-ZHER2:342-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a KD of 6±2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe 111In-/125I-HP2 to ZHER2:342-SR-HP1 pre-treated cells was demonstrated. 111In-ZHER2:342-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of 111In-ZHER2:342-SR-HP1. The complementary PNA probe 111In/125I-HP2 accumulated in SKOV-3 xenografts when ZHER2:342-SR-HP1 was injected 4 h earlier. The tumor accumulation of 111In/125I-HP2 was negligible without ZHER2:342-SR-HP1 pre-injection. The uptake of 111In-HP2 in SKOV-3 xenografts was 19±2 %ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys. PMID:26722376

  20. Edwardsiella tarda Endocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality

    PubMed Central

    Litton, Kayleigh M.; Rogers, Bret A.

    2016-01-01

    Edwardsiella tarda is a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- (111In-) labeled white blood cell (WBC) scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp.) for diagnosing acute and chronic infection. We describe a case of suspected E. tarda prosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of 111In-labeled WBC scintigraphy. PMID:26885418

  1. Edwardsiella tarda Endocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality.

    PubMed

    Litton, Kayleigh M; Rogers, Bret A

    2016-01-01

    Edwardsiella tarda is a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- ((111)In-) labeled white blood cell (WBC) scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp.) for diagnosing acute and chronic infection. We describe a case of suspected E. tarda prosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of (111)In-labeled WBC scintigraphy. PMID:26885418

  2. Visualization of a prosthetic vascular graft due to platelet contamination during /sup 111/Indium-labeled leukocyte scintigraphy

    SciTech Connect

    Oates, E.; Ramberg, K.

    1988-09-01

    A prosthetic axillo-femoral bypass graft was visualized during /sup 111/In-labeled leukocyte scintigraphy in a patient referred for possible abdominal abscess. The presence of significant cardiac blood-pool activity raised the possibility that this uptake was due to deposition of contaminating labeled platelets rather than labeled leukocytes. An analysis of a small sample of the patient's blood confirmed that the circulating activity was due to labeled platelets. Increased activity along prosthetic vascular grafts in patients undergoing /sup 111/In-labeled leukocyte scintigraphy may be due to adherent platelet, and not indicative of infection.

  3. 18. Historic American Buildings Survey PHOTOCOPY OF SKETCH BY FREDERIK ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. Historic American Buildings Survey PHOTOCOPY OF SKETCH BY FREDERIK GJESSING USED TO ILLUSTRATE HIS ARTICLE 'OBSERVATIONS ON THE OLDEST HOUSE, ST. AUGUSTINE,' (p.111) IN EVOLUTION OF THE OLDEST HOUSE TALLAHASSEE, FLORIDA: DEPARTMENT FLORIDA STATE UNIVERSITY, 1962 - Gonzalez-Alvarez House, 14 Saint Francis Street, Saint Augustine, St. Johns County, FL

  4. Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction

    SciTech Connect

    Jain, D.; Crawley, J.C.; Lahiri, A.; Raftery, E.B. )

    1990-02-01

    The results of indium-111 ({sup 111}In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received {sup 111}In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal {sup 111}In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when {sup 111}In-antimyosin is injected six days postinfarction.

  5. A simple digital TDPAC spectrometer

    NASA Astrophysics Data System (ADS)

    Webb, T. A.; Nikkinen, Leo; Gallego, Juan; Ryan, D. H.

    2013-05-01

    We present a simplified digital time differential perturbed γ - γ angular correlation (TDPAC) spectrometer that demonstrates that such instruments can be built using primarily commercial components and with relatively modest coding effort. The system handles data rates of 70 kcps/detector with a timing resolution of better than 500 ps, and has been used with both 111In and 181Hf.

  6. Magnetic properties of rare-earth permanent magnets under a high radiation environment

    NASA Astrophysics Data System (ADS)

    Tanigaki, M.; Takamiya, K.; Komeno, Y.; Taniguchi, A.; Ohkubo, Y.

    An study on the demagnetization of rare-earth permanent magnets under high radiation environment is started from the microscopic point of view. The demagnetization of NEOMAX is successfully induced by the well defined neutron field produced by the 5 MW reactor in Kyoto University. Preliminary TDPAC measurement of 111Cd(←111In) in NEOMAX, including demagnetized one, is reported.

  7. Magnetic properties of rare-earth permanent magnets under a high radiation environment

    NASA Astrophysics Data System (ADS)

    Tanigaki, M.; Takamiya, K.; Komeno, Y.; Taniguchi, A.; Ohkubo, Y.

    2007-04-01

    An study on the demagnetization of rare-earth permanent magnets under high radiation environment is started from the microscopic point of view. The demagnetization of NEOMAX is successfully induced by the well defined neutron field produced by the 5 MW reactor in Kyoto University. Preliminary TDPAC measurement of 111Cd(←111In) in NEOMAX, including demagnetized one, is reported.

  8. Chelate conjugates of monoclonal antibodies for imaging lymphoid structures in the mouse

    SciTech Connect

    Goodwin, D.A.; Meares, C.F.; McCall, M.J.; Haseman, M.K.; McTigue, M.; Diamanti, C.I.; Chaovapong, W.

    1985-05-01

    Radiolabeling of a mouse monoclonal antibody (MoAb) specific for the mouse histocompatibility alloantigen lA/sup k/ expressed by the B lymphocytes of BALB/k and C3H mice but not BALB/c mice was performed by mixing the chelate-labeled anti (..cap alpha..) lA/sup k/ MoAb with purified, no-carrier-added /sup 111/In citrate. The organ, spleen, and lymph node distribution of intravenously and subcutaneously administered /sup 111/In..cap alpha..lA/sup k/ MoAb was compared in mice, two lA/sup k/ positive and one lA/sup k/ negative strains, and to /sup 125/l..cap alpha..lA/sup k/ MoAb in one 1A/sup K/ positive strain. The /sup 111/In..cap alpha.. 1A/sup K/ MoAb was more stable in vivo compared to /sup 125/I..cap alpha.. 1A/sup K/ MoAb as shown by a much slower excretion and a higher absolute uptake in lymph nodes and spleen. Potential clinical applications of /sup 111/In..cap alpha.. lymphocyte MoAb include localization of normal lymph nodes and T and B cell leukemias and lymphomas, as well as detecting lymphatic metastases of other cancers.

  9. In vivo kinetics of radiolabeled monoclonal anti-CEA antibodies in animal models

    SciTech Connect

    Hagan, P.L.; Halpern, S.E.; Chen, A.; Krishnan, L.; Frincke, J.; Bartholomew, R.M.; David, G.S.; Carlo, D.

    1985-12-01

    Studies were performed to determine the effect of the radiolabel and circulating carcinoembryonic antigen (CEA) on the pharmacodynamics of monoclonal anti-CEA antibodies (MoAbs). The studies were performed in normal BALB/c mice and in nude mice bearing human colon tumors. Three different tumors were used, each of which produced CEA levels characteristic of that particular tumor's secretory rate. The CEJ-326 MoAb labeled with either 111In or 125I was used in all studies. Circulating CEA induced the removal of 125I and 111In MoAbs from the vascular compartment. Liver concentrations of 111In increased and 125I levels decreased as the CEA secretory rate of the tumor rose. This indicates that circulating CEA complexes form in the vascular compartment which, in an animal model, are removed by the liver and spleen. This results in decreased tumor uptake of the labeled MoAb. The iodinated MoAb complexes are dehalogenated while the 111In is retained by the liver. This dehalogenation may account for the relatively low liver activity observed in radioimmunoimaging with intact radioiodinated anti-CEA MoAbs, provided the CEA complexes are similarly removed from the vascular compartment by the human liver.

  10. In vivo integrity of polymer-coated gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Kreyling, Wolfgang G.; Abdelmonem, Abuelmagd M.; Ali, Zulqurnain; Alves, Frauke; Geiser, Marianne; Haberl, Nadine; Hartmann, Raimo; Hirn, Stephanie; de Aberasturi, Dorleta Jimenez; Kantner, Karsten; Khadem-Saba, Gülnaz; Montenegro, Jose-Maria; Rejman, Joanna; Rojo, Teofilo; de Larramendi, Idoia Ruiz; Ufartes, Roser; Wenk, Alexander; Parak, Wolfgang J.

    2015-07-01

    Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles (198Au) and engineered an 111In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for 198Au and 111In showed partial removal of the polymer shell in vivo. While 198Au accumulates mostly in the liver, part of the 111In shows a non-particulate biodistribution similar to intravenous injection of chelated 111In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

  11. Localization of Neuroendocrine Tumors Using Somatostatin Receptor Imaging With Indium-111-Pentetreotide (OctreoScan).

    PubMed

    Ellison; Schirmer; Olsen; Pozderac; Hinkle; Hill; O'Dorisio; O'Dorisio

    1997-01-01

    BACKGROUND: Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. METHODS: The authors have investigated the use of 111-In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. RESULTS: The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111-In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111-In-pentetreotide was a 4-mm duodenal tumor. CONCLUSIONS: Scintigraphy with 111-In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases. PMID:10763002

  12. Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

    SciTech Connect

    Kulkarni, P.V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R.W.; Mathews, D.; Mason, R.P.; Oz, O.K.

    2003-08-26

    Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga)

  13. Detection of cardiac transplant rejection with radiolabeled lymphocytes. [Rats

    SciTech Connect

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-03-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.

  14. Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

    SciTech Connect

    Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

    1987-01-01

    We performed the biodistribution and imaging studies of /sup 111/In and /sup 67/Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of /sup 67/Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both /sup 111/In and /sup 67/Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of /sup 67/Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of /sup 67/Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of /sup 67/Ga citrate. The imaging studies performed with /sup 111/In T4NMPYP and /sup 67/Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of /sup 111/In T4NMPYP. 15 refs., 3 figs., 5 tabs.

  15. Use of indium 111-labeled white blood cell scan in the diagnosis of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram

    SciTech Connect

    Chinsky, K.; Goodenberger, D.M. )

    1991-03-01

    Opportunistic infections are common in patients after renal transplantation. This report describes a case of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram and normal arterial oxygenation. An abnormal 111In-white blood cell scan led to the discovery of a pulmonary source of his recurrent fevers.

  16. Service Learning in an Undergraduate Social Work Research Course

    ERIC Educational Resources Information Center

    Postlethwait, Ariana

    2012-01-01

    The current study examined student experiences (n = 111) in an undergraduate social work (BSW) research seminar in which a service learning (SL) project was the primary focus. Student groups of approximately six or seven worked with local agencies to develop a research plan for the agency. Students found the SL project to be a positive experience.…

  17. Indium-111-leukocyte/technetium-99m-MDP bone and magnetic resonance imaging: Difficulty of diagnosing osteomyelitis in patients with neuropathic osteoarthropathy

    SciTech Connect

    Seabold, J.E.; Flickinger, F.W.; Kao, S.C.; Gleason, T.J.; Kahn, D.; Nepola, J.V.; Marsh, J.L. )

    1990-05-01

    Fourteen patients (16 sites) with clinical and/or radiographic evidence of neuropathic osteoarthropathy (Charcot joints) were evaluated with combined indium-111-leukocyte ({sup 111}In-WBC) and technetium-99m-methylene diphosphonate ({sup 99m}Tc-MDP) bone imaging for suspected osteomyelitis. Magnetic resonance (MR) images were obtained in seven patients. Using a positive bone culture as the criterion for the presence of osteomyelitis, there were four true-positive studies, six true-negative sites, and one false-negative {sup 111}In-WBC study. Five of 16 sites (31%) had false-positive {sup 111}In-WBC uptake at noninfected sites. There were four true-positive and three false-positive MR studies. All false-positives showed at least moderately abnormal findings by both techniques at sites of rapidly progressing osteoarthropathy of recent onset. In this preliminary study, both techniques appear to be sensitive for detection of osteomyelitis, and a negative study makes osteomyelitis unlikely. However, the findings of {sup 111}In-WBC/{sup 99m}Tc-MDP and MR images at sites of rapidly progressing, noninfected neuropathic osteoarthropathy may be indistinguishable from those of osteomyelitis.

  18. Indium-111-chloride and three-phase bone scintigraphy: A comparison for imaging experimental osteomyelitis

    SciTech Connect

    Hoskinson, J.J.; Daniel, G.B.; Patton, C.S. )

    1991-01-01

    To investigate the utility of indium-111-chloride ({sup 111}In-Cl) imaging in detecting osteomyelitis complicating surgical or fracture sites, the proximal tibia of 11 dogs were experimentally infected with Staphylococcus aureus after creation of a cortical defect. The contralateral limb served as a sham-operated control. Animals were serially imaged by radiography, three-phase technetium-99m-methylene diphosphonate (99mTc-MDP) scintigraphy, and {sup 111}In-Cl scintigraphy. There was a significant difference between infected (1.93) and noninfected (1.32) limb's tibia/femur count density ratios on 24-hr (p = 0.0001) and 72-hr (p = 0.0001) {sup 111}In-Cl images. A smaller difference was found for 99mTc-MDP bone-phase tibia/femur ratios (p = 0.0199). Using receiver operator characteristic analysis of tibia/femur ratios, a sensitivity of 61%, specificity of 88%, and positive (75%) and negative (79%) predictive values were determined for the 24-hr {sup 111}In-Cl images. Indium-111-chloride was superior to 99mTc-MDP in differentiating infected and noninfected operative sites.

  19. Indium-111-labeled leukocyte scintigraphy: diagnosis of subperiosteal abscesses complicating osteomyelitis in a child

    SciTech Connect

    Outwater, E.; Oates, E.; Sarno, R.C.

    1988-11-01

    Preoperative /sup 111/In-labeled leukocyte scintigraphy demonstrated extensive subperiosteal abscesses complicating acute bilateral tibial osteomyelitis in a child. Plain radiographs showed only marked soft-tissue swelling; three-phase bone scintigraphy depicted both hot and cold areas consistent with acute osteomyelitis.

  20. Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion

    SciTech Connect

    Saverymuttu, S.H.; Camilleri, M.; Rees, H.; Lavender, J.P.; Hodgson, H.J.; Chadwick, V.S.

    1986-05-01

    Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease. The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation. We now report a prospective study comparing 111In-granulocyte scanning with endoscopy, histology, and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease. In 52 patients with Crohn's disease or ulcerative colitis, disease extent and severity were assessed macroscopically, histologically, or by scanning using a numerical grading system. Excellent correlations were found between both endoscopy and histology and 111In scans (r = 0.90 (endoscopy) and r = 0.90 (histology) for extent; r = 0.86 and r = 0.91 for disease activity). Severity graded by scanning also showed a close correlation with fecal 111In-granulocyte excretion (r = 0.90). Indium 111-granulocyte scans are a rapid, accurate, noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease.

  1. Radioimmunoimaging of lung vessels: An approach using indium-111-labeled monoclonal antibody to angiotensin-converting enzyme

    SciTech Connect

    Danilov, S.M.; Martynov, A.V.; Klibanov, A.L.; Slinkin, M.A.; Sakharov, I.Yu.; Malov, A.G.; Sergienko, V.B.; Vedernikov, A.Yu.; Muzykantov, V.R.; Torchilin, V.P.

    1989-10-01

    A murine monoclonal antibody against human angiotensin-converting enzyme was radiolabeled with {sup 111}In via diethylenetriaminepentaacetic acid without substantial loss of antigen-binding capacity. This monoclonal antibody designated 9B9 cross-reacted with rat and monkey angiotensin-converting enzyme. Indium-111-labeled 9B9 selectively accumulated 10-20 times greater in the lung than in blood or other organs following intravenous administration in rats. Kinetics of lung accumulation and blood clearance were studied for {sup 111}In-9B9-antibody and compared to that of {sup 125}I-labeled 9B9 in rat. Highly specific accumulation of {sup 111}In-9B9-antibody in the lung of Macaca Rhesus monkeys after intravenous injection was monitored by gamma-imaging. Images of {sup 111}In-labeled antibody 9B9 biodistribution in monkey lung noticeably differ from the images of biodistribution of {sup 99m}Tc-labeled albumin microspheres. This difference may provide information concerning the state of the endothelium of lung capillaries, which is different from the blood flow characteristics determined with routine microsphere technique.

  2. Vacuum synthesis of magnetic aluminum phthalocyanine on Au(111).

    PubMed

    Hong, I-Po; Li, Na; Zhang, Ya-Jie; Wang, Hao; Song, Huan-Jun; Bai, Mei-Lin; Zhou, Xiong; Li, Jian-Long; Gu, Gao-Chen; Zhang, Xue; Chen, Min; Gottfried, J Michael; Wang, Dong; Lü, Jing-Tao; Peng, Lian-Mao; Hou, Shi-Min; Berndt, Richard; Wu, Kai; Wang, Yong-Feng

    2016-08-16

    Air-unstable magnetic aluminum phthalocyanine (AlPc) molecules are prepared by an on-surface metalation reaction of phthalocyanine with aluminum (Al) atoms on Au(111) in ultrahigh vacuum. Experiments and density functional theory calculations show that an unpaired spin is located on the conjugated isoindole lobes of the molecule rather than at the Al position. PMID:27406881

  3. Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis

    SciTech Connect

    Williams, K.J.; Vallabhajosula, S.; Rahman, I.U.; Donnelly, T.M.; Parker, T.S.; Weinrauch, M.; Goldsmith, S.J.

    1988-01-01

    The metabolism of infused /sup 111/In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t/sub 1/2/) for clearance of /sup 111/In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits. By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue sores. Disappearance of excess plasma cholesterol was > 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative ..gamma.. camera imaging, hepatic trapping of /sup 111/In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance. Aortic uptake of /sup 111/In was < 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, the results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia.

  4. Role of phosphate-containing compounds in the transfer of indium-111 and gallium-67 from transferrin to ferritin.

    PubMed

    Weiner, R E

    1989-01-01

    Physiologic concentrations of ATP stimulate the translocation of gallium-67 (67Ga) from human transferrin (TF) to horse ferritin (HoFE). The mechanism of this translocation was examined. One millimolar ATP did not speed the binding of 67Ga or indium-111 (111In) to HoFE. ATP and pyrophosphate (PPi) at 1 mM, did not form high affinity complexes with 67Ga or 111In. ATP and PPi interacted directly with the [67Ga]TF complex and could within minutes increase the amount of nonprotein-bound 67Ga. Serum HCO3- concentration, 30 mM, prevented the ATP-induced dissociation of 67Ga from TF, whereas intracellular concentrations (0.4 and 5 mM) did not. Using a dialysis technique, ATP also stimulated the translocation of 111In from TF to HoFE; however, this process was much slower than with 67Ga. ATP caused an increase in the nonprotein-bound 111In compared to the control. These results suggest the formation of nonprotein-bound nuclide by these phosphate-containing compounds in a kinetically labile form is important to the translocation mechanism. PMID:2536083

  5. High Efficiency Diffusion Molecular Retention Tumor Targeting

    PubMed Central

    Guo, Yanyan; Yuan, Hushan; Cho, Hoonsung; Kuruppu, Darshini; Jokivarsi, Kimmo; Agarwal, Aayush; Shah, Khalid; Josephson, Lee

    2013-01-01

    Here we introduce diffusion molecular retention (DMR) tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT) injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding) and RAD (control) probes were synthesized bearing DOTA (for 111 In3+), a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or IV methods was assessed by surface fluorescence, biodistribution of [111In] RGD and [111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by IV). The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide), which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters) for radiotherapy, or the delivery of photosensitizers to tumors accessible to light. PMID:23505478

  6. Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

    NASA Astrophysics Data System (ADS)

    Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

    2003-08-01

    Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

  7. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    SciTech Connect

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-03-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with /sup 125/I or /sup 111/In was compared to that of (/sup 67/Ga)citrate and (/sup 99m/Tc)albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, (/sup 111/In)IgG showed greater accumulation at the lesion than (/sup 99m/Tc)HSA (p less than 0.01). Both (/sup 125/I)IgG and (/sup 111/In)IgG showed greater accumulation than (/sup 67/Ga)citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of (/sup 67/Ga)citrate or (/sup 99m/Tc)HSA (p less than 0.01). At all imaging times, (/sup 67/Ga)citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, (/sup 111/In)IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.

  8. Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer

    PubMed Central

    Ciprotti, Marika; Tebbutt, Niall C.; Lee, Fook-Thean; Lee, Sze-Ting; Gan, Hui K.; McKee, David C.; O'Keefe, Graeme J.; Gong, Sylvia J.; Chong, Geoffrey; Hopkins, Wendie; Chappell, Bridget; Scott, Fiona E.; Brechbiel, Martin W.; Tse, Archie N.; Jansen, Mendel; Matsumura, Manabu; Kotsuma, Masakatsu; Watanabe, Rira; Venhaus, Ralph; Beckman, Robert A.; Greenberg, Jonathan; Scott, Andrew M.

    2015-01-01

    Purpose CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC). Patients and Methods Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 (111In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days. Results Nineteen patients were enrolled. 111In-CS-1008 uptake in tumor was observed in only 12 patients (63%). 111In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. 111In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti–CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with 111In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor–5 expression in archived tumor samples did not correlate with 111In-CS-1008 uptake (P = .5) or tumor response (P = .6). Conclusion Death-receptor–5 imaging with 111In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC. PMID:26124477

  9. Immunospecific saturable clearance mechanisms for indium-111-labeled anti-melanoma monoclonal antibody 96. 5 in humans

    SciTech Connect

    Murray, J.L.; Lamki, L.M.; Shanken, L.J.; Blake, M.E.; Plager, C.E.; Benjamin, R.S.; Schweighardt, S.; Unger, M.W.; Rosenblum, M.G.

    1988-08-01

    Liver uptake of 111In-labeled monoclonal antibodies (MoAb) remains a significant problem in radioimaging studies to date. To determine if the observed liver uptake of an 111In-labeled anti-melanoma antibody 96.5 (111In-96.5) was dependent on the presence of hepatic antigen or on recognition of circulating murine antibody, escalating doses of an unlabeled nonimmunoreactive MoAb (NIR-MoAb) were administered to 18 patients with metastatic malignant melanoma either 1 or 24 h prior to an infusion of 1 mg of 111In-96.5. The number of metastases imaged, pharmacokinetics, and the ratio of radioactivity (expressed as average counts/pixel) in liver (L), spleen (S), bone (B), and kidney (K) compared to blood pool (heart = H) were examined. Results were prospectively compared with data from six patients who received immunoreactive unlabeled 96.5 prior to 111In-96.5. Increasing dose or changes in the preinfusion time of NIR-MoAb had no significant effect on the biodistribution of 111In-96.5. In contrast, patients who received unlabeled, immunoreactive 96.5 prior to 111In-96.5 infusion demonstrated a significant drop (P less than 0.001) in the liver/heart ratio of radioactivity (2.81 +/- 0.35 (SEM)) compared to patients receiving the identical dose of NIR-MoAb (10.35 +/- 1.33). Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t1/2 both decreased when 96.5 was administered compared to NIR-MoAb. In addition, a 4-fold increase in concentration X time was obtained after 96.5 antibody was administered compared to NIR-MoAb. More metastases were imaged in patients receiving preinfusions of 96.5 (23 of 28) than in patients receiving NIR-MoAb (10 of 18; P less than 0.05).

  10. Development of antibody directed nanoparticles for cancer therapy

    NASA Astrophysics Data System (ADS)

    Ivkov, R.; DeNardo, S. J.; Meirs, L. A.; Natarajan, A.; DeNardo, G. L.; Gruettner, C.; Foreman, A. R.

    2007-02-01

    The pharmacokinetics, tumor uptake, and biologic effects of inductively heating 111In-chimeric L6 (ChL6) monoclonal antibody (mAb)-linked iron oxide nanoparticle (bioprobes) by externally applied alternating magnetic fields (AMF) were studied in athymic mice bearing human breast cancer HBT 3477 xenografts. In addition, response was correlated with calculated total deposited heat dose. Methods: Using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide HCl, 111In-7,10-tetraazacyclododecane-N, N',N'',N'''-tetraacetic acid-ChL6 was conjugated to the carboxylated polyethylene glycol on dextran-coated iron oxide 20-nm particles, one to two mAbs per nanoparticle. After magnetic purification and sterile filtration, pharmacokinetics, histopathology, and AMF/bioprobe therapy were done using 111In-ChL6 bioprobe doses (20 mcg/2.2 mg ChL6/ bioprobe), i.v. with 50 mcg ChL6 in athymic mice bearing HBT 3477; a 153 kHz AMF was given 72 hours postinjection for therapy with amplitudes of 1,300, 1,000, or 700 Oe. Weights, blood counts, and tumor size were monitored and compared with control mice receiving nothing, or AMF, or bioprobes alone. Results: 111In-ChL6 bioprobe binding in vitro to HBT 3477 cells was 50% to 70% of that of 111In-ChL6. At 48 hours, tumor, lung, kidney, and marrow uptakes of the 111In-ChL6 bioprobes were not different from that observed in prior studies of 111In-ChL6. Significant therapeutic responses from AMF/bioprobe therapy were shown compared with no treatment. In addition, greatest therapeutic benefit was observed for the 700 Oe treatment cohort. Toxicity was only seen in the 1,300 Oe AMF cohort, with 4 of 12 immediate deaths associated with skin erythema and petechiae. Conclusion: This study shows that mAb-conjugated nanoparticles (bioprobes), when given i.v., escape into the extravascular space and bind to cancer cell membrane antigen.Thus, bioprobes can be used in concert with externally applied AMF to deliver thermoablative cancer therapy. Therapeutic benefit

  11. Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate.

    PubMed

    Zhang, Libin; Zhang, Rui; Yang, Jiyuan; Wang, Jiawei; Kopeček, Jindřich

    2016-08-10

    Recently, we developed 2nd generation backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates which contain enzymatically cleavable sequences (GFLG) in both polymeric backbone and side-chains. This design allows using polymeric carriers with molecular weights above renal threshold without impairing their biocompatibility, thereby leading to significant improvement in therapeutic efficacy. For example, 2nd generation HPMA copolymer-epirubicin (EPI) conjugates (2P-EPI) demonstrated complete tumor regression in the treatment of mice bearing ovarian carcinoma. To obtain a better understanding of the in vivo fate of this system, we developed a dual-labeling strategy to simultaneously investigate the pharmacokinetics and biodistribution of the polymer carrier and drug EPI. First, we synthesized two different types of dual-radiolabeled conjugates, including 1) (111)In-2P-EPI-(125)I (polymeric carrier 2P was radiolabeled with (111)In and drug EPI with (125)I), and 2) (125)I-2P-EPI-(111)In (polymeric carrier 2P was radiolabeled with (125)I and drug EPI with (111)In). Then, we compared the pharmacokinetics and biodistribution of these two dual-labeled conjugates in female nude mice bearing A2780 human ovarian carcinoma. There was no significant difference in the blood circulation between polymeric carrier and payload; the carriers ((111)In-2P and (125)I-2P) showed similar retention of radioactivity in both tumor and major organs except kidney. However, compared to (111)In-labeled payload EPI, (125)I-labeled EPI showed lower radioactivity in normal organs and tumor at 48h and 144h after intravenous administration of conjugates. This may be due to different drug release rates resulting from steric hindrance to the formation of enzyme-substrate complex as indicated by cleavage experiments with lysosomal enzymes (Tritosomes). A slower release rate of EPI(DTPA)(111)In than EPI(Tyr)(125)I was observed. It may be also due to in vivo catabolism and

  12. Synergism of peptide receptor-targeted Auger electron radiation therapy with anti-angiogenic compounds in a mouse model of neuroendocrine tumors

    PubMed Central

    2014-01-01

    Background Neuroendocrine tumors are well vascularized and express specific cell surface markers, such as somatostatin receptors and the glucagon-like peptide-1 receptor (GLP-1R). Using the Rip1Tag2 transgenic mouse model of pancreatic neuroendocrine tumors (pNET), we have investigated the potential benefit of a combination of anti-angiogenic treatment with targeted internal radiotherapy. Methods [Lys40(Ahx-DTPA-111In)NH2]-exendin-4, a radiopeptide that selectively binds to GLP-1R expressed on insulinoma and other neuroendocrine tumor cells, was co-administered with oral vatalanib (an inhibitor of vascular endothelial growth factor receptors (VEGFR)) or imatinib (a c-kit/PDGFR inhibitor). The control groups included single-agent kinase inhibitor treatments and [Lys40(Ahx-DTPA-natIn)NH2]-exendin-4 monotherapy. For biodistribution, Rip1Tag2 mice were pre-treated with oral vatalanib or imatinib for 0, 3, 5, or 7 days at a dose of 100 mg/kg. Subsequently, [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 was administered i.v., and the biodistribution was assessed after 4 h. For therapy, the mice were injected with 1.1 MBq [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 and treated with vatalanib or imatinib 100 mg/kg orally for another 7 days. Tumor volume, tumor cell apoptosis and proliferation, and microvessel density were quantified. Results Combination of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 and vatalanib was significantly more effective than single treatments (p < 0.05) and reduced the tumor volume by 97% in the absence of organ damage. The pre-treatment of mice with vatalanib led to a reduction in the tumor uptake of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4, indicating that concomitant administration of vatalanib and the radiopeptide was the best approach. Imatinib did not show a synergistic effect with [Lys40(Ahx-DTPA-111In)NH2]-exendin-4. Conclusion The combination of 1.1 MBq of [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 with 100 mg/kg vatalanib had the same effect on a neuroendocrine tumor

  13. Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas

    PubMed Central

    Brom, Maarten; Joosten, Lieke; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C.

    2012-01-01

    For peptide receptor targeting usually internalizing agonists are selected. There is increasing evidence that non-internalizing receptor antagonists can be used for this purpose. We investigated whether the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin(9-39) can be used for in vivo targeting of GLP-1R expressing tumours and compared the in vitro and in vivo characteristics to the GLP-1R agonists exendin-3 and exendin-4. The binding and internalization kinetics of labelled [Lys40(DTPA)]exendin-3, [Lys40(DTPA)]exendin-4 and [Lys40(DTPA)]exendin(9-39) were determined in vitro using INS-1 cells. The in vivo targeting properties of [Lys40(111In-DTPA)]exendin-3, [Lys40(111In-DTPA)]exendin-4 and [Lys40(111In-DTPA)]exendin(9-39) were examined in BALB/c nude mice with subcutaneous INS-1 tumours. natIn-labelled [Lys40(DTPA)]exendin-3, [Lys40(DTPA)]exendin-4 and [Lys40(DTPA)]exendin(9-39) exhibited similar IC50 values (13.5, 14.4 and 13.4 nM, respectively) and bound to 26 × 103, 41 × 103 and 37 × 103 receptors/cell, respectively. [Lys40(111In-DTPA)]exendin-3 and [Lys40(111In-DTPA)]exendin-4 showed rapid in vitro binding and internalization kinetics, whereas [Lys40(111In-DTPA)]exendin(9-39) showed lower binding and minimal internalization in vitro. In mice, high specific uptake of [Lys40(111In-DTPA)]exendin-3 (25.0 ± 6.0 %ID/g) in the tumour was observed at 0.5 h p.i. with similar uptake up to 4 h p.i.. [Lys40(111In-DTPA)]exendin-4 showed higher tumour uptake at 1 and 4 h p.i. (40.8 ± 7.0 and 41.9 ± 7.2 %ID/g, respectively). Remarkably, [Lys40(111In-DTPA)]exendin(9-39) showed only low specific uptake in the tumour at 0.5 h p.i. (3.2 ± 0.7 %ID/g), rapidly decreasing over time. In conclusion, the GLP-1R agonists [Lys40(DTPA)]exendin-3 and [Lys40(DTPA)]exendin-4 labelled with 111In could be useful for in vivo GLP-1R targeting, whereas [Lys40(DTPA)]exendin(9-39) is not suited for in vivo targeting of the GLP-1R. PMID:22434628

  14. Indium-111-Photofrin-II scintillation scan

    SciTech Connect

    Origitano, T.C.; Karesh, S.M.; Reichman, O.H.; Henkin, R.E.; Caron, M.J.

    1989-04-01

    Photodynamic therapy is under intense investigation as an adjuvant treatment for malignant glial tumors of the central nervous system. Photofrin-II (HpD-II) is currently the most actively investigated photosensitizing agent. A crucial issue regarding the safe and efficacious usage of HpD-II-based photodynamic therapy is the individual in vivo kinetics of tumor uptake and retention, compared with normal brain clearance. The optimal time for photoactivation of sensitized tumor must be known to ensure a high target-to-nontarget ratio, resulting in the maximal tumor destruction while preserving normal brain. Our laboratory developed a radionuclide scan based on 111indium (111In)-labeled HpD-II to evaluate HpD-II localization and clearance noninvasively within a canine model of intracerebral gliosarcoma. Synthesis of the 111In-HpD-II complex in greater than 90% yield is achieved by a simple, rapid labeling method. Radiochemical purity and stability were verified by high-performance liquid chromatography. Using the canine model of intracerebral gliosarcoma, we followed the uptake of 111In-HpD-II in tumors with serial scintillation scanning. Localization of the tumor by 111In-HpD-II has been verified by contrast-enhanced computed tomographic scan followed by gross and histological examination of the enhancing brain region. Total body biodistribution of 111In-HpD-II at various times after injection has been evaluated. The ratio of uptake in tumor compared with surrounding brain peaked at 72 hours after injection. The knowledge of regional distribution and concentration of a photosensitizing agent within a tumor mass and surrounding brain allows for the most efficacious timing and localization of a photoactivating source.

  15. Targeting HER2

    PubMed Central

    Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W

    2010-01-01

    The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama. PMID:20716957

  16. Evaluation of primary lung cancer with indium 111 anti-carcinoembryonic antigen (type ZCE-025) monoclonal antibody scintigraphy

    SciTech Connect

    Krishnamurthy, S.; Morris, J.F.; Antonovic, R.; Ahmed, A.; Galey, W.T.; Duncan, C.; Krishnamurthy, G.T. )

    1990-02-01

    A study was undertaken to test whether indium 111 (111In)-labeled anti-carcinoembryonic antigen (CEA) (type ZCE 025) monoclonal intact antibody (MoAb) would concentrate in primary lung cancer enabling its detection and localization by scintigraphy. The scintigraphic results were correlated with chest radiograph, computed tomograph (CT), bronchoscopy, surgical resection, and tumor CEA analysis. Twenty adult male patients with clinical suspicion of primary lung cancer were studied. Each subject was infused with 4 to 5 mCi of 111In anti-CEA ZCE 025 MoAb, and planar and tomographic scintiphotos were obtained on days 3 and 6 or 7 postinfusion. The scintigraphy was true-positive in 12 of 16 patients with primary lung cancer, eight of nine patients with squamous cell carcinoma, and four of seven with adenocarcinoma; it was true-negative in three of four patients with benign lung disease with an overall accuracy of 75%. In seven patients with confirmed primary lung cancer, but with negative bronchoscopic findings, the scintigraphy was true-positive in four. In 11 patients with definitely positive or suspicious malignancy by bronchoscopy the monoclonal scintigraphy was positive in eight. In true-positive cases, the location and size of the lesion by 111In anti-CEA ZCE 025 MoAb imaging correlated well with CT findings and also tumor mass at surgery. Only one of 12 tumors stained positive for CEA had serum CEA levels greater than 10 ng/ml, indicating nonleakage of the tumor antigen into general circulation in early lung cancer. It is concluded that 111In anti-CEA ZCE 025 MoAb planar and tomographic imaging shows potential to serve as a noninvasive diagnostic test in the evaluation of primary lung cancer. The lung lesion is likely to be malignant if it concentrates 111In anti-CEA ZCE 025 MoAb and benign if it does not.

  17. Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor-imaging studies

    SciTech Connect

    Brechbiel, M.W.; Gansow, O.A.; Atcher, R.W.; Schlom, J.; Esteban, J.; Simpson, D.E.; Colcher, D.

    1986-07-30

    To investigate the /sup 111/In labeling of tumor-localizing monoclonal antibodies (MoAb), the chelate 1-(p-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid (p-SCN-Bz-DPTA) (1) and its EDTA analogue (2) have been synthesized. By the use of a MoAb (B72.3) specific for a high molecular weight antigen (TAG-72) on cells of a colorectal carcinoma grown in nude mice, optimal chemical conditions for MoAb conjugation of those ligands and of the dicyclic and isobutylcarboxy carbonic anhydrides of DTPA and subsequent /sup 111/In labeling were determined. All conjugates were shown by a competitive binding assay to retain their specificity and activity in vitro when less than one ligand is protein coupled both prior to and after /sup 111/In labeling. Chemical methods for purification of the MoAb were systematically investigated by injection of purified immunoprotein into athymic mice bearing LS-174T tumors that express the TAG-72 antigen. Tissue distribution studies revealed that simple addition of EDTA to labeled immunoglobulins was ineffective at complexing indium not linked to protein by chelates. Similarly, gel chromatography (Sephadex G-50) was not sufficient; rather, size exclusion HPLC had to be employed to remove unreacted /sup 111/In and aggregated antibody. To compare the relative utility of the four chelates for /sup 111/In diagnostic radioimmunoimaging, scintigraphic images of tumor-bearing mice were obtained and evaluated along with tissue distributions. Results showed that clear images of these solid tissue tumors free of extraneous radiation could be obtained only by using p-SCN-Bz-DTPA purified by HPLC. Methods developed are now being employed in clinical trials for diagnosis of human colorectal cancer. 71 references, 5 figures, 1 table.

  18. Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018

    SciTech Connect

    Murray, J.L.; Rosenblum, M.G.; Lamki, L.; Glenn, H.J.; Krizan, Z.; Hersh, E.M.; Plager, C.E.; Bartholomew, R.M.; Unger, M.W.; Carlo, D.J.

    1987-01-01

    Radioimmunolocalization of an /sup 111/In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single. i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi /sup 111/In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel, testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p less than 0.005). A significant correlation was observed between tumor uptake of /sup 111/In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T1/2 of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of /sup 111/In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with /sup 111/In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

  19. Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis.

    PubMed Central

    Williams, K J; Vallabhajosula, S; Rahman, I U; Donnelly, T M; Parker, T S; Weinrauch, M; Goldsmith, S J

    1988-01-01

    The metabolism of infused 111In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t1/2) for clearance of 111In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits (means +/- SEM; n = 4). By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue stores. Disappearance of excess plasma cholesterol was greater than 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative gamma camera imaging, hepatic trapping of 111In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance, acquiring 22.0% +/- 1.7% (WHHL) and 16.8% +/- 1.0% (normal of total 111In. Aortic uptake of 111In was less than 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, our results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia. PMID:3422421

  20. Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer

    NASA Astrophysics Data System (ADS)

    Hoang, Nu Bryan

    Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes. This thesis describes the synthesis and characterization of a targeted block copolymer micelle system based on poly(ethylene glycol)-block -poly(epsilon-caprolactone) labeled with the radionuclide Indium-111 (111In). The incorporation of the imageable component, 111In permits pursuit of image-guided drug delivery for real-time monitoring of tumor localization and intratumoral distribution. Intracellular trafficking of drugs and therapies such as Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. HER2 specific antibodies (trastuzumab fab fragments) and nuclear localization signal peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake was HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS resulted in a significant increase in nuclear uptake of the radionuclide 111In. Successful nuclear targeting was shown to improve the antiproliferative effect of the Auger electrons. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and 111In in all breast cancer cell lines evaluated. Imaging enabled the accurate quantification of the specific tumor uptake of the micelles and visualization of their degree of tumor penetration in relation to

  1. Contribution of endothelial selectins and alpha 4 integrins to eosinophil trafficking in allergic and nonallergic inflammatory reactions in skin.

    PubMed

    Teixeira, M M; Hellewell, P G

    1998-09-01

    The role of endothelial selectins in mediating eosinophil recruitment was assessed using the trafficking of 111In-labeled blood eosinophils in mouse skin. An intradermal injection of chemoattractants (leukotriene B4, macrophage inflammatory protein-l alpha, and eotaxin) resulted in a rapid accumulation of 111In eosinophils that was reduced 49 to 91% by anti-P-selectin mAb. An anti-E-selectin mAb was ineffective, although a combined E- and P-selectin blockade resulted in >95% inhibition of all responses. The accumulation of a pulse of 111In eosinophils at sites of active cutaneous anaphylaxis (ACA) at 4 to 8 h and at 20 to 24 h after Ag challenge was completely dependent upon E- and P-selectin in combination, but not in isolation. In contrast, at 20 to 24 h after Ag challenge in a delayed-type hypersensitivity (DTH) reaction in skin, 111In eosinophil accumulation was largely independent of endothelial selectins, even when L-selectin was also blocked. An anti-alpha 4 integrin mAb significantly reduced 111In eosinophil trafficking in both allergic reactions but was slightly more effective in the DTH reaction compared with the ACA reaction. These results show that P-selectin and to a lesser extent E-selectin mediate eosinophil recruitment in skin in acute inflammatory reactions. In allergic, late-onset inflammatory reactions, neither P- nor E-selectin alone are sufficient to mediate eosinophil accumulation; when combined, they are essential for trafficking in ACA but are less important in the DTH reaction. Whether alpha 4 integrin-based strategies will be more effective than selectin-based strategies at inhibiting eosinophil recruitment in human disease remains to be determined. PMID:9725251

  2. Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

    PubMed

    Schillaci, Orazio; DeNardo, Gerald L; DeNardo, Sally J; Goldstein, Desiree S; Kroger, Linda A; O'Donnell, Robert T; Lamborn, Kathleen R

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes. PMID:17803447

  3. LCP nanoparticle for tumor and lymph node metastasis imaging

    NASA Astrophysics Data System (ADS)

    Tseng, Yu-Cheng

    A lipid/calcium/phosphate (LCP) nanoparticle formulation (particle diameter ˜25 nm) has previously been developed to delivery siRNA with superior efficiency. In this work, 111In was formulated into LCP nanoparticles to form 111In-LCP for SPECT/CT imaging. With necessary modifications and improvements of the LCP core-washing and surface-coating methods, 111In-LCP grafted with polyethylene glycol exhibited reduced uptake by the mononuclear phagocytic system. SPECT/CT imaging supported performed biodistribution studies, showing clear tumor images with accumulation of 8% or higher injected dose per gram tissue (ID/g) in subcutaneous, human-H460, lung-cancer xenograft and mouse-4T1, breast cancer metastasis models. Both the liver and the spleen accumulated ˜20% ID/g. Accumulation in the tumor was limited by the enhanced permeation and retention effect and was independent of the presence of a targeting ligand. A surprisingly high accumulation in the lymph nodes (˜70% ID/g) was observed. In the 4T1 lymph node metastasis model, the capability of intravenously injected 111In-LCP to visualize the size-enlarged and tumor-loaded sentinel lymph node was demonstrated. By analyzing the SPECT/CT images taken at different time points, the PK profiles of 111In-LCP in the blood and major organs were determined. The results indicated that the decrement of 111In-LCP blood concentration was not due to excretion, but to tissue penetration, leading to lymphatic accumulation. Larger LCP (diameter ˜65 nm) nanoparticles were also prepared for the purpose of comparison. Results indicated that larger LCP achieved slightly lower accumulation in the tumor and lymph nodes, but much higher accumulation in the liver and spleen; thus, larger nanoparticles might not be favorable for imaging purposes. We also demonstrated that LCP with a diameter of ˜25 nm were better able to penetrate into tissues, travel in the lymphatic system and preferentially accumulate in the lymph nodes due to 1) small

  4. Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours

    NASA Astrophysics Data System (ADS)

    Gnanasegaran, Gopinath

    Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the

  5. Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings.

    PubMed

    Adams, S; Baum, R P; Hertel, A; Schumm-Draeger, P M; Usadel, K H; Hör, G

    1998-09-01

    Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node

  6. Pretargeted dual-modality immuno-SPECT and near-infrared fluorescence imaging for image-guided surgery of prostate cancer.

    PubMed

    Lütje, Susanne; Rijpkema, Mark; Goldenberg, David M; van Rij, Catharina M; Sharkey, Robert M; McBride, William J; Franssen, Gerben M; Frielink, Cathelijne; Helfrich, Wijnand; Oyen, Wim J G; Boerman, Otto C

    2014-11-01

    Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either (111)In-RDC018 or (111)In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of (111)In-RDC018 and (111)In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 ± 3.7% ID/g at 2 hours postinjection), comparable with (111)In-IMP288 (9.1 ± 2.8% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label (111)In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by image-guided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dual-modality imaging approach in prostate cancer. PMID:25252911

  7. Bifunctional Phage-Based Pretargeted Imaging of Human Prostate Carcinoma Bifunctional Phage Based Pretargeted Imaging

    PubMed Central

    Newton-Northup, Jessica R.; Figueroa, Said D.; Quinn, Thomas P.; Deutscher, Susan L.

    2009-01-01

    Introduction Two-step and three-step pretargeting systems utilizing biotinylated prostate tumor-homing bacteriophage (phage) and 111In-radiolabeled- streptavidin or biotin were developed for use in cancer radioimaging. The in vivo selected prostate carcinoma-specific phage (G1) displaying up to five copies of the peptide IAGLATPGWSHWLAL, was the focus of the present study. Methods The ability of G1 phage to extravasate and target prostate tumor cells was investigated using immunohistochemistry. G1 phage were biotinylated, streptavidin was conjugated to diethylenetriaminepentaacetic acid (DTPA), and biotin was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Biodistribution studies and single photon emission computed tomography (SPECT)/CT imaging of xenografted PC-3 tumors via two-step pretargeted 111In-labeled streptavidin and three-step pretargeted 111In-labeled biotin were performed in SCID mice to determine the optimal pretargeting method. Results The ability of G1 phage to extravasate the vasculature and bind directly to human PC-3 prostate carcinoma tumor cells in vivo was demonstrated via immunocytochemical analysis. Comparative biodistribution studies of the two-step and three-step pretargeting strategies indicated increased PC-3 human prostate carcinoma tumor uptake in SCID mice of 4.34 ±0.26 %ID/g at 0.5 hours post-injection of 111In radiolabeled biotin (utilized in a three-step protocol) compared to that of 0.67 ±0.06 %ID/g at twenty four hour postinjection of 111In radiolabeled streptavidin (employed in a two-step protocol). In vivo SPECT/CT imaging of xenografted PC-3 tumors in SCID mice with the three-step pretargeting method was superior to that of the two-step pretargeting method, and, importantly, blocking studies demonstrated specificity of tumor uptake of 111In-labeled biotin in the three-step pretargeting scheme. Conclusion This study demonstrates the use of multivalent bifunctional phage in a three

  8. SPECT assay of radiolabeled monoclonal antibodies

    SciTech Connect

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  9. SPECT assay of radiolabeled monoclonal antibodies. Comprehensive progress report, September 1989--February 1992

    SciTech Connect

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  10. Biomedical research with cyclotron produced radionuclides. Progress report, February 1, 1981-December 31, 1981

    SciTech Connect

    Laughlin, J.S.

    1981-09-01

    Progress is reported in the following areas: evaluation of chemotherapeutic regimens in solid tumors using /sup 13/N-labelled amino acids; organ imaging with /sup 13/N-labelled L-amino acids; imaging with /sup 111/In-labelled-autologous platelets; synthesis and biological studies of /sup 111/In-labelled ammonia and L-amino acids; synthesis and evaluation for pancreatic imaging of /sup 11/C-labelled amino acides; radioisotope monitoring of myocardiol function; synthesis of /sup 11/C-labelled precursor compounds; reduction of radiation exposure through automation and remote control; development of an anhydrous /sup 18/F target; evaluation of radiolabelled 5-fluorouracils for scintigraphy; and methods of data analysis, modeling, and unproving instrumentation for positron-emission tomography. (EDB)

  11. Dual-radiolabeled nanoparticle SPECT probes for bioimaging

    NASA Astrophysics Data System (ADS)

    Black, Kvar C. L.; Akers, Walter J.; Sudlow, Gail; Xu, Baogang; Laforest, Richard; Achilefu, Samuel

    2014-12-01

    A gold nanoparticle was radiolabeled with 125I and 111In and functionalized with an MMP9-cleavable peptide to form a multispectral SPECT imaging contrast agent. Peptide cleavage from the nanoprobe by MMP9 was observed in vitro, and distinct pharmacokinetic properties of the contrast agent were observed between tumors with high or low MMP9 expression.A gold nanoparticle was radiolabeled with 125I and 111In and functionalized with an MMP9-cleavable peptide to form a multispectral SPECT imaging contrast agent. Peptide cleavage from the nanoprobe by MMP9 was observed in vitro, and distinct pharmacokinetic properties of the contrast agent were observed between tumors with high or low MMP9 expression. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05269b

  12. TDPAC study of Cd-doped SnO

    NASA Astrophysics Data System (ADS)

    Muñoz, E. L.; Carbonari, A. W.; Errico, L. A.; Bibiloni, A. G.; Petrilli, H. M.; Rentería, M.

    The combination of hyperfine techniques and ab initio calculations has been shown to be a powerful tool to unravel structural and electronic characterizations of impurities in solids. A recent example has been the study of Cd-doped SnO, where ab initio calculations questioned previous TDPAC assignments of the electric-field gradient (EFG) in 111In-implanted Sn-O thin films. Here we present new TDPAC experiments at 111In-difused polycrystalline SnO. A reversible temperature dependence of the EFG was observed in the range 295--900 K. The TDPAC results were compared with theoretical calculations performed with the full-potential linearized augmented plane wave (FP-LAPW) method, in the framework of the density functional theory. Through the comparison with the theoretical results, we infer that different electronic surroundings around Cd impurities can coexist in the SnO sample.

  13. TDPAC study of Cd-doped SnO

    NASA Astrophysics Data System (ADS)

    Muñoz, E. L.; Carbonari, A. W.; Errico, L. A.; Bibiloni, A. G.; Petrilli, H. M.; Rentería, M.

    2007-07-01

    The combination of hyperfine techniques and ab initio calculations has been shown to be a powerful tool to unravel structural and electronic characterizations of impurities in solids. A recent example has been the study of Cd-doped SnO, where ab initio calculations questioned previous TDPAC assignments of the electric-field gradient (EFG) in 111In-implanted Sn-O thin films. Here we present new TDPAC experiments at 111In-difused polycrystalline SnO. A reversible temperature dependence of the EFG was observed in the range 295-900 K. The TDPAC results were compared with theoretical calculations performed with the full-potential linearized augmented plane wave (FP-LAPW) method, in the framework of the density functional theory. Through the comparison with the theoretical results, we infer that different electronic surroundings around Cd impurities can coexist in the SnO sample.

  14. Uptake of indium-111-labeled monoclonal antibody ZME-018 as a function of tumor size in a patient with melanoma

    SciTech Connect

    Macey, D.J.; Denardo, S.J.; Denardo, G.L.; Goodnight, J.K.; Unger, M.W.

    1988-01-01

    The accumulation of an Indium-111-labeled monoclonal antibody (MoAb), ZME-018, in melanoma tumors in a patient was determined by sequential, quantitative gamma camera imaging. The amount and concentration of In-111 in each tumor changed in a characteristic pattern with time, reaching a peak at day 3 followed by a steady clearance. The concentration of In-111 in the tumor and the ratios of tumor to whole-body or blood decreased as the size of the tumor increased. These results were interpreted to indicate that the fraction of active, perfused tumor decreased as the melanoma lesions increased in size. The maximum number of MoAb molecules bound per melanoma cell was calculated to be abut 35,000. The implications of these observations for radioimmunoimaging and therapy are significant.

  15. In vivo targeting of HER2-positive tumor using 2-helix affibody molecules.

    PubMed

    Ren, Gang; Webster, Jack M; Liu, Zhe; Zhang, Rong; Miao, Zheng; Liu, Hongguang; Gambhir, Sanjiv S; Syud, Faisal A; Cheng, Zhen

    2012-07-01

    Molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression has drawn significant attention because of the unique role of the HER2 gene in diagnosis, therapy and prognosis of human breast cancer. In our previous research, a novel cyclic 2-helix small protein, MUT-DS, was discovered as an anti-HER2 Affibody analog with high affinity through rational protein design and engineering. MUT-DS was then evaluated for positron emission tomography (PET) of HER2-positive tumor by labeling with two radionuclides, 68Ga and 18F, with relatively short half-life (t1/2<2 h). In order to fully study the in vivo behavior of 2-helix small protein and demonstrate that it could be a robust platform for labeling with a variety of radionuclides for different applications, in this study, MUT-DS was further radiolabeled with 64Cu or 111In and evaluated for in vivo targeting of HER2-positive tumor in mice. Design 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated MUT-DS (DOTA-MUT-DS) was chemically synthesized using solid phase peptide synthesizer and I2 oxidation. DOTA-MUT-DS was then radiolabeled with 64Cu or 111In to prepare the HER2 imaging probe (64Cu/111In-DOTA-MUT-DS). Both biodistribution and microPET imaging of the probe were evaluated in nude mice bearing subcutaneous HER2-positive SKOV3 tumors. DOTA-MUT-DS could be successfully synthesized and radiolabeled with 64Cu or 111In. Biodistribution study showed that tumor uptake value of 64Cu or 111In-labeled DOTA-MUT-DS was 4.66±0.38 or 2.17±0.15%ID/g, respectively, in nude mice bearing SKOV3 xenografts (n=3) at 1 h post-injection (p.i.). Tumor-to-blood and tumor-to-muscle ratios for 64Cu-DOTA-MUT-DS were attained to be 3.05 and 3.48 at 1 h p.i., respectively, while for 111In-DOTA-MUT-DS, they were 2.04 and 3.19, respectively. Co-injection of the cold Affibody molecule ZHER2:342 with 64Cu-DOTA-MUT-DS specifically reduced the SKOV3 tumor uptake of the probe by 48%. 111In

  16. Electric quadrupole interactions in nano-structured SnO 2 as measured with PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Ramos, J. M.; Carbonari, A. W.; Costa, M. S.; Saxena, R. N.

    2010-04-01

    Measurements of the electric quadrupole interaction were used to characterize pure and cobalt-doped samples of SnO2 prepared by the sol-gel method. Perturbed gamma-gamma angular correlation (PAC) spectroscopy using 111In-111Cd probe nuclei was employed for these measurements. A methodology was developed for sample preparation that were prepared by sol-gel method from pure metallic Sn (99.9999%) and Co (99.9998%) as starting materials. Carrier-free 111In was added to the precursor sol-gel solution prior to the formation of gel. PAC measurements were carried out to follow the formation of the SnO2. PAC measurements were carried out in the temperature range from 10 k to 1123 K and the results show that the electric quadrupole frequency depends on the annealing temperature.

  17. A weak magnetism observed in SnO2 doped with Fe by means of Perturbed Gamma-Gamma Angular Correlation and Mössbauer Spectroscopy

    NASA Astrophysics Data System (ADS)

    Ramos, J. M.; Carbonari, A. W.; Martucci, T.; Costa, M. S.; Cabrera-Pasca, G. A.; Macedo, M. A. V.; Saxena, R. N.

    Nano-structured samples of SnO2 doped with Fe prepared by the sol-gel method were studied by the Perturbed Gamma-Gamma Angular Correlation (PAC) Spectroscopy using 111In (111Cd) probe nuclei as well as by 57Fe Mšssbauer spectroscopy. The samples were prepared from very pure metallic Sn and Fe. Carrier-free 111In nuclei were introduced during the sol-gel process of sample preparation for PAC measurements. The PAC measurements were carried out after annealing the samples at different temperatures and the results show a combined electric quadrupole and magnetic dipole interaction for probe nuclei that do not occupy the regular Sn sites. The hyperfine parameters revealed weak magnetic interactions.

  18. New cross section data and review of production routes of medically used 110mIn

    NASA Astrophysics Data System (ADS)

    Tárkányi, F.; Takács, S.; Ditrói, F.; Hermanne, A.; Baba, M.; Mohsena, B. M. A.; Ignatyuk, A. V.

    2015-05-01

    Evaluation of nuclear data for production routes of 110mIn is in progress in the frame of an IAEA Coordinated Research Project (CRP). New experimental cross section data for the indirect natIn(p,x)110Sn-110mIn and for the direct 107Ag(α,n)110mIn and 109Ag(3He,2n)110mIn production routes and for the satellite impurity reactions 107Ag(α,xn)110g,109In and 109Ag(3He,xn)110g,111,109In have been measured by using the activation method, stacked foil irradiation technique and gamma-ray spectrometry. Additional data are reported for production of the 111In diagnostic gamma-emitter via the 109Ag(α,2n)111In reaction. The earlier experimental data were critically reviewed in order to prepare recommended data and optimal production parameters for the different routes.

  19. Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: The effect of antibiotic treatment

    SciTech Connect

    Chung, C.J.; Hicklin, O.A.; Payan, J.M.; Gordon, L. )

    1991-01-01

    To determine the sensitivity and specificity of the indium-111-({sup 111}In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed. Of 41 consecutive {sup 111}In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics. The average duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans for graft infection were found. By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%.

  20. Indium-111-labeled leukocyte scintigraphy in hemodialysis access-site infection

    SciTech Connect

    Palestro, C.J.; Vega, A.; Kim, C.K.; Vallabhajosula, S.; Goldsmith, S.J. )

    1990-03-01

    Bacterial sepsis, a significant complication of chronic hemodialysis, is generally the result of infection at the vascular access site. We retrospectively reviewed the utility of indium-111-(111In) labeled autologous leukocyte scintigraphy in 26 patients (30 scans) with synthetic vascular grafts, on chronic hemodialysis, in whom hemodialysis access site infection was a diagnostic consideration. Leukocyte scintigraphy correctly identified all fifteen access-site infections; there was one false-positive study, for an overall sensitivity and specificity of 100% and 93%, respectively. Of particular significance is the fact that in nine (60%) of the fifteen access-site infections, physical examination was normal. Our data indicate that 111In-labeled leukocyte scintigraphy is a useful procedure for the diagnosis of hemodialysis access-site infection, and it is especially valuable when physical examination of the access site is normal.

  1. A sensitive new method of ex vivo platelet deposition

    SciTech Connect

    Badimon, L.; Fuster, V.; Dewanjee, M.K.; Romero, J.C.

    1982-10-01

    In 1978, an in vivo quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, researches labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, researches quantitated the /sup 111/In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. Researchers found that the /sup 111/In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system.

  2. Substance P-induced inflammatory responses in guinea-pig skin: the effect of specific NK1 receptor antagonists and the role of endogenous mediators.

    PubMed Central

    Walsh, D T; Weg, V B; Williams, T J; Nourshargh, S

    1995-01-01

    1. The sensory neuropeptide substance P (SP), when released from sensory nerves, has been implicated in the development of neurogenic inflammation. In the present study, using an in vivo model system, we have characterized and investigated the mechanisms underlying SP-induced leukocyte accumulation and oedema formation in the guinea-pig. 2. Intradermally injected SP (i.d., 10(-13) - 10(-9) mol per site), induced a dose- and time-dependent accumulation of 111In-neutrophils, 111In-eosinophils and oedema formation as measured by the local accumulation of i.v. injected 125I-albumin. The leukocyte accumulation evoked by SP was significant at 10(-10) and 10(-9) mol per site, whereas oedema formation was significant at the lowest dose tested (10(-13) mol per site). 3. The NK1 receptor antagonists, CP-96,345 (1 mg kg-1, i.v.) and RP-67,580 (10 micrograms per site, i.d.), significantly attenuated the oedema formation induced by the lower doses of SP. Oedema formation and leukocyte accumulation induced by 10(-9) mol per site SP were unaffected by either antagonist. 4. SP-elicited responses were not significantly affected by the platelet activating factor (PAF) receptor antagonist, UK-74,505 (2.5 mg kg-1, i.v.) or the H1 histamine receptor antagonist, chlorpheniramine (10(-8) mol per site, i.d.). However, the 111In-eosinophil accumulation, but not the 111In-neutrophil accumulation or oedema formation, induced by SP was significantly inhibited by the specific 5-lipoxygenase (5-LO) inhibitor, ZM-230,487 (10(-8) mol per site, i.d.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541689

  3. Relationship between intestinal permeability to ( sup 51 Cr)EDTA and inflammatory activity in asymptomatic patients with Crohn's disease

    SciTech Connect

    Pironi, L.; Miglioli, M.; Ruggeri, E.; Levorato, M.; Dallasta, M.A.; Corbelli, C.; Nibali, M.G.; Barbara, L. )

    1990-05-01

    The relationship between intestinal permeability to an oral dose (100 mu Ci) of (51CR)EDTA and the inflammatory activity of Crohn's disease was studied in 63 adult patients (32 unresected and 31 resected) who underwent 162 evaluations. The results of the (51CR)EDTA test were compared with the serum levels of the acute-phase reactant proteins (APRP) and with the result of the (111In)leukocyte scanning, respectively, as an indirect and direct method to assess intestinal inflammation. In a group of healthy adult controls, the upper normal value for the 24-hr urinary (51CR)EDTA excretion was 3.61 (97.5% percentile) and the mean coefficient of variation was 21%. Sensitivity and specificity of the (51CR)EDTA test in identifying active inflammation expressed by increased serum levels of APRP were, respectively, 97% and 54% in the unresected group and 68% and 52% in the resected group of patients. The low specificity of the test was due to the presence of increased (51CR)EDTA urinary excretion in about half the cases with normal serum levels of APRP. The (111In)leukocyte scanning was performed in a subgroup of 11 patients (three unresected and eight resected) with normal serum levels of APRP, six with increased and five with normal (51CR)EDTA urinary excretion. All six patients with increased intestinal permeability had a positive 111In image of mild to moderate degree of activity. A positive 111In scan was present in two of the five patients with normal permeability; these were two resected patients.

  4. Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas

    PubMed Central

    Kryza, David; Debordeaux, Frédéric; Azéma, Laurent; Hassan, Aref; Paurelle, Olivier; Schulz, Jürgen; Savona-Baron, Catherine; Charignon, Elsa; Bonazza, Pauline; Taleb, Jacqueline; Fernandez, Philippe; Janier, Marc; Toulmé, Jean Jacques

    2016-01-01

    The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor. PMID:26901393

  5. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor–Positive Tumors

    PubMed Central

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J.G.; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C.

    2011-01-01

    In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor–positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET–computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor–mediated uptake (p = .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor–positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor–positive tumors in humans. PMID:21439259

  6. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery

    PubMed Central

    Woods, A.; Patel, A.; Spina, D.; Riffo-Vasquez, Y.; Babin-Morgan, A.; de Rosales, R.T.M.; Sunassee, K.; Clark, S.; Collins, H.; Bruce, K.; Dailey, L.A.; Forbes, B.

    2015-01-01

    The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin nanoparticles was investigated following a single administration of 2, 20, and 390 μg/mouse, showing no inflammatory response (TNF-α and IL-6, cellular infiltration and protein concentration) compared to vehicle controls at the two lower doses, but elevated mononucleocytes and a mild inflammatory effect at the highest dose tested. The biodistribution and clearance of 111In labelled albumin solution and nanoparticles over 48 h following a single pulmonary administration to mice was investigated by single photon emission computed tomography and X-ray computed tomography imaging and terminal biodistribution studies. 111In labelled albumin nanoparticles were cleared more slowly from the mouse lung than 111In albumin solution (64.1 ± 8.5% vs 40.6 ± 3.3% at t = 48 h, respectively), with significantly higher (P < 0.001) levels of albumin nanoparticle-associated radioactivity located within the lung tissue (23.3 ± 4.7%) compared to the lung fluid (16.1 ± 4.4%). Low amounts of 111In activity were detected in the liver, kidneys, and intestine at time points > 24 h indicating that small amounts of activity were cleared from the lungs both by translocation across the lung mucosal barrier, as well as mucociliary clearance. This study provides important information on the fate of albumin vehicles in the lungs, which may be used to direct future formulation design of inhaled nanomedicines. PMID:25980621

  7. Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases

    SciTech Connect

    Patt, Y.Z.; Lamki, L.M.; Shanken, J.; Jessup, J.M.; Charnsangavej, C.; Ajani, J.A.; Levin, B.; Merchant, B.; Halverson, C.; Murray, J.L. )

    1990-07-01

    We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.

  8. Imaging findings and pharmacokinetics of 111-indium ZME-018 monoclonal antibody (MoAb) in malignant melanoma

    SciTech Connect

    Murray, J.L.; Rosenblum, M.; Lamki, L.; Haynie, T.P.; Glenn, H.; Jahns, M.; Plager, C.; Hersh, E.M.; Unger, M.; Carlo, D.L.

    1985-05-01

    13 patients with metastatic melanoma were studied using 5 mCi of In-111 labeled MoAb ZME-018 which reacts with GP 240 melanoma-associated antigen. The MoAb was infused over 2 h at doses of 2.5 mg (5 pts), 5 mg (5 pts), and 10 mg (3 pts). Total body tomograms and planar spot views with region of interest analysis were performed at 4, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours when the background activity was less. 20 of 46 (43%) previously documented metastases were identified. More sites imaged with increasing concentrations of MoAB, I.E., 25% at 2.5 mg; 67% at 5 mg; 70% at 10 mg. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg. In two instances, uptake of 111-In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for 111-In in plasma was 24.5 +- 2.7 hours. The apparent volume of distribution (Vd) was 4.03 +- 5iota similar to the plasma value, and the calculated clearance rate for 111-In label was 0.0259 + 0.002 ml/kg/min. Mean urinary excretion of 111-In label was 8.7 +- 0.6% of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. ZME 018 was cleared more rapidly from plasma, compared to previous studies with P97 antimelanoma MoAb.

  9. Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas.

    PubMed

    Kryza, David; Debordeaux, Frédéric; Azéma, Laurent; Hassan, Aref; Paurelle, Olivier; Schulz, Jürgen; Savona-Baron, Catherine; Charignon, Elsa; Bonazza, Pauline; Taleb, Jacqueline; Fernandez, Philippe; Janier, Marc; Toulmé, Jean Jacques

    2016-01-01

    The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor. PMID:26901393

  10. Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF.

    PubMed

    Kareem, Heewa; Sandström, Karl; Elia, Ronny; Gedda, Lars; Anniko, Matti; Lundqvist, Hans; Nestor, Marika

    2010-04-01

    Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of (125)I-labeled EGF. The anti-EGFR Affibody molecule (Z(EGFR:955))(2) was then assessed as a blocking agent of (111)In-labeled EGF in a dual isotope study (50, 100, and 200 microg, preadministered 30 or 60 min before (111)In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased (125)I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 microg (Z(EGFR:955))(2) as a blocking agent 30 min before the (111)In-EGF decreased the uptake of (111)In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (Z(EGFR:955))(2) shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging. PMID:20358420

  11. Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer.

    PubMed

    Josefsson, Anders; Nedrow, Jessie R; Park, Sunju; Banerjee, Sangeeta Ray; Rittenbach, Andrew; Jammes, Fabien; Tsui, Benjamin; Sgouros, George

    2016-01-15

    The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radionuclide Indium-111 ((111)In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of (111)In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Coinjection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of (111)In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of (111)In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. PMID:26554829

  12. A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

    PubMed Central

    Raubitschek, Andrew; Yamauchi, Dave; Williams, Lawrence E.; Wu, Anna M.; Yazaki, Paul; Shively, John E.; Colcher, David; Somlo, George

    2010-01-01

    Abstract Purpose The purposes of this study were to evaluate the organ biodistribution, pharmacokinetics, immunogenicity, and tumor uptake of 111Indium (111In)-MxDTPA-trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers and to determine whether 90Y-MxDTPA-trastuzumab should be evaluated in subsequent clinical therapy trials. Experimental Design Patients with HER2-overexpressing breast cancers who were to undergo planned trastuzumab therapy first received unlabeled trastuzumab (4–8 mg/kg IV), followed 4 hours later by 5 mCi 111In-MxDTPA-trastuzumab (10 mg antibody). Serial blood samples, 24-hour urine collections, and nuclear scans were performed at defined time points for 7 days. Results Eight (8) patients received 111In-MxDTPA-trastuzumab, which was well tolerated with no adverse side-effects. Three (3) of 7 patients with known lesions demonstrated positive imaging on nuclear scans. No antiantibody responses were observed for 2 months postinfusion. Organ doses (cGy/mCi) assuming radiolabeling with 90Y were 19.9 for heart wall, 17.6 for liver, 4.6 for red marrow, and 2.8 for the whole body. Tumor doses ranged from 24 to 172 cGy/mCi. Conclusions In summary, results from this study indicate that 90Y-MxDTPA-trastuzumab is an appropriate agent to evaluate in therapy trials. No evidence of an immune response to 111In-MxDTPA-trastuzumab was detected, predicting for the ability to administer multiple cycles. With the exception of cardiac uptake, pharmacokinetics and organ biodistribution were comparable to other 90Y-labeled monoclonal antibodies previously evaluated in the clinic. Cardiac uptake was comparable to hepatic uptake and therefore predicted to not be prohibitively high as to result in dose-limiting cardiotoxicity. PMID:20707718

  13. OctreoScan 111 for imaging of a somatostatin receptor-positive islet cell tumor in rat.

    PubMed

    Bruns, C; Stolz, B; Albert, R; Marbach, P; Pless, J

    1993-01-01

    Somatostatin (SRIF) receptors are present in a variety of human tumors such as pituitary and endocrine pancreatic tumors, brain tumors, small cell lung cancers and malignant breast tumors. The 111In-labeled SRIF analog SDZ 215-811 (OctreoScan 111) binds with a high affinity to somatostatin receptors and exhibits SRIF-like biological properties, as demonstrated by the inhibition of growth hormone release from pituitary cells. We report here the in vitro characterization of SDZ 215-811 and the in vivo imaging of an islet cell tumor grown in rats using [111In]SDZ 215-811. In vitro autoradiographies revealed a high density of SRIF receptors on the pancreatic tumor tissue. As early as 5 min after intravenous injection of [111In]SDZ 215-811 into tumor-bearing rats, the tumors were clearly localized by gamma-camera scintigraphy. Even 24 h post injection, the islet cell tumor was still detectable. The radioligand was mainly cleared from the circulation via the kidneys, with a rapid alpha-phase (t1/2 = 5.6 min) and a slow elimination phase (t1/2 = 7.3 h). Biodistribution studies revealed a relatively high accumulation of radioactivity in the kidneys, but low uptake into the liver and the intestine. High uptake of [111In]SDZ 215-811 was observed for the tumor tissue (0.92 +/- 0.07% ID/g; 1 h post injection). Interestingly, a tumor load of 0.14 +/- 0.01% ID/g was still measured after 24 h. The tumor/blood ratio was 4.93 after 24 h, indicating specific accumulation of radioactivity in the islet cell tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8392488

  14. Bladder pheochromocytoma: case presentation and the use of OctreoScan for localization of extra-adrenal tumor sites in a pediatric patient.

    PubMed

    Fournier, José R; Baez-Trinidad, Luis; Acosta, Alex; Marrero, Miguel; Correa-Rivas, María; Rodríguez-Becerra, Javier; Nieves, Francisco

    2008-03-01

    An eleven year old boy presented with headaches and dizziness associated to micturition. On radiologic imaging, he was found with a bladder mass. The biochemical work up was suggestive of pheochromocytoma. An OctreoScan (111In-pentreotide) was used to rule out metastatic extension or other extra-adrenal locations of the pheochromocytoma. OctreoScan data correlated well with other radiologic studies, operative findings and with the final diagnosis, validating its use on pediatric patients. PMID:18450243

  15. Influence of Histidine-Containing Tags on the Biodistribution of ADAPT Scaffold Proteins.

    PubMed

    Lindbo, Sarah; Garousi, Javad; Åstrand, Mikael; Honarvar, Hadis; Orlova, Anna; Hober, Sophia; Tolmachev, Vladimir

    2016-03-16

    Engineered scaffold proteins (ESP) are high-affinity binders that can be used as probes for radionuclide imaging. Histidine-containing tags enable both efficient purification of ESP and radiolabeling with (99m)Tc(CO)3. Earlier studies demonstrated that the use of a histidine-glutamate-histidine-glutamate-histidine-glutamate (HE)3-tag instead of the commonly used hexahistidine (H6)-tag reduces hepatic uptake of radiolabeled ESP and short peptides. Here, we investigated the influence of histidine-containing tags on the biodistribution of a novel type of ESP, ADAPTs. A series of anti-HER2 ADAPT probes having H6- or (HE)3-tags in the N-termini were prepared. The constructs, (HE)3-ADAPT6 and H6-ADAPT6, were labeled with two different nuclides, (99m)Tc or (111)In. The labeling with (99m)Tc(CO)3 utilized the histidine-containing tags, while (111)In was attached through a maleimido derivative of DOTA conjugated to the N-terminus. For (111)In-labeled ADAPTs, the use of (HE)3 provided a significantly (p < 0.05) lower hepatic uptake at 1 h after injection, but there was no significant difference in hepatic uptake of (111)In-(HE)3-ADAPT6 and H6-ADAPT6 at later time points. Interestingly, in the case of (99m)Tc, (99m)Tc(CO)3-H6-ADAPT6 provided significantly (p < 0.05) lower uptake in a number of normal tissues and was more suitable as an imaging probe. Thus, the influence of histidine-containing tags on the biodistribution of the novel ADAPT scaffold proteins was different compared to its influence on other ESPs studied so far. Apparently, the effect of a histidine-containing tag on the biodistribution is highly dependent on the scaffold composition of the ESP. PMID:26781756

  16. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    SciTech Connect

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  17. 40 CFR 63.11502 - What definitions apply to this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...), subpart WW (§ 63.1061), 40 CFR 60.111b, subpart F (§ 63.101), subpart G (§ 63.111), subpart FFFF (§ 63.2550), as specified after each term: Administrator (§ 63.2) Article (40 CFR 372.3) Boiler (§ 63.111... in the CAA, § 63.2, subpart SS (§ 63.981), subpart WW (§ 63.1061), 40 CFR 60.111b, subpart F (§...

  18. The CO/Pt(111) Puzzle

    SciTech Connect

    FEIBELMAN,PETER J.; HAMMER,B.; NORSHOV,J.K.; WAGNER,F.; SCHEFFLER,M.; STUMPF,R.; DUMESIC,J.; WATWE,R.

    2000-07-12

    Notwithstanding half a dozen theoretical publications, well-converged density-functional calculations, whether based on a local or generalized-gradient exchange-correlation potential, whether all-electron or employing pseudopotentials underestimate CO's preference for low-coordination binding sites on Pt(111) and vicinals to it. For example, they imply that CO should prefer hollow- to atop-site adsorption on Pt(111), in apparent contradiction to a host of low temperature experimental studies.

  19. Differentiation between meningiomas and other CNS tumors by simultaneous somatostatin receptor and brain scintigraphy

    SciTech Connect

    Haldemann, A.R.; Luescher, D.; Sulzer, M.

    1994-05-01

    Since the differentiation between meningiomas and some other CNS tumors may be difficult in certain localizations, biopsy is mandatory, even in patients with meningiomas who are to be treated with percutaneous radiotherapy alone. The high density of somatostatin receptors (SSR) in meningiomas has led us to compare patients with meningiomas and other CNS tumors by simultaneous SSR and brain scintigraphy (BS) using 74 MBq 111In octreotide and 740 MBq 99mTc DTPA injected two hours later. SPECT was performed on a 3-head gamma camera 4 hours after 111In octreotide injection in multiple peak acquisition mode in 35 patients with radiologically documented CNS tumors. In positive scans, a tumor ROI was defined manually in the transverse 111In slice with highest tumor contrast and the identical tumor ROI was transferred to the corresponding 99mTc slice. A SSR to BS index was then calculated from the ratio of 111In to 99mTc counts after normalizing for identical total counts in the slices. in negative scans, the SSR to BS index was set to be 1.0. In 7 meningiomas, the SSR to BS index was 2.64{plus_minus}0.76. In 28 other CNS tumors (7 gliomas I-111, 4 neurinomas, 3 glial reactions, 3 metastases, 3 gliomas IV, 2 ependymomas, 1 chordoma, 1 NHL; plus 4 inoperable, radiologically diagnosed glioblastomas) 1.06{plus_minus}0.13. Thus, a highly significant difference was found between these two groups (p<0.0001). It is concluded that combined SSR and BS allows excellent discrimination between meningiomas and other CNS tumors and may become a non-invasive alternative to biopsy in selected clinical situations.

  20. Method for preparing radionuclide-labeled chelating agent-ligand complexes

    DOEpatents

    Meares, Claude F.; Li, Min; DeNardo, Sally J.

    1999-01-01

    Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

  1. Uptake of indium-111-labeled platelets and indium-111 oxine by murine kidneys after total-body irradiation

    SciTech Connect

    Ebbe, S.; Taylor, S.; Maurer, H.; Kullgren, B.

    1996-08-01

    Radiation nephropathy is a well-known late manifestation of renal irradiation in human beings and experimental animals. Its pathogenesis is unclear, but vascular injury may play a role. Endothelial cells have been demonstrated to manifest a variety of abnormalities within hours of exposure to radiation. In the present experiments mice were exposed to lethal doses of whole-body radiation, and the distribution of {sup 111}In-labeled platelets was evaluated during the first week after irradiation. The purpose was to determine if early abnormalities of endothelial cells would be manifested by altered sequestration of platelets in kidneys and other organs. It was found that the indium accumulated in the kidneys of irradiated mice to a greater extent than in nonirradiated mice, but the pattern of accumulation differed from that seen after injection of radiolabeled platelets. Renal hyperemia was not demonstrable with {sup 51}Cr-labeled red cells, renal vascular permeability was not detected with {sup 125}I-labeled albumin, and the pattern of renal uptake of plasma proteins labeled albumin, and the pattern of renal uptake of plasma proteins labeled with {sup 59}Fe {sup 111}In did not coincide with that seen from {sup 111}In administered as labeled platelets or oxine. Renal uptake of {sup 111}In-oxine was not associated with alterations in urinary or fecal excretion or an increase in total-body retention of the radioisotope. The findings are consistent with the notion that renal vascular injury at the time of irradiation results in accumulation of platelets or platelet constituents during the first week after total-body irradiation of mice. 29 refs., 5 figs., 3 tabs.

  2. Image-Guided Radiotherapy for Prostate Cancer: A Prospective Trial of Concomitant Boost Using Indium-111-Capromab Pendetide (ProstaScint) Imaging

    SciTech Connect

    Wong, William W.; Schild, Steven E.; Vora, Sujay A.; Ezzell, Gary A.; Nguyen, Ba D.; Ram, Panol C.; Roarke, Michael C.

    2011-11-15

    Purpose: To evaluate, in a prospective study, the use of {sup 111}In-capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. Methods and Materials: From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and {sup 111}In-capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in {sup 111}In-capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10-20 ng/mL or Gleason 7 disease. Results: Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. Conclusion: Concomitant boost to areas showing increased uptake in {sup 111}In-capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years.

  3. Shifting the Voltage Drop in Electron Transport Through a Single Molecule.

    PubMed

    Karan, Sujoy; Jacob, David; Karolak, Michael; Hamann, Christian; Wang, Yongfeng; Weismann, Alexander; Lichtenstein, Alexander I; Berndt, Richard

    2015-07-01

    A Mn-porphyrin was contacted on Au(111) in a low-temperature scanning tunneling microscope (STM). Differential conductance spectra show a zero-bias resonance that is due to an underscreened Kondo effect according to many-body calculations. When the Mn center is contacted by the STM tip, the spectrum appears to invert along the voltage axis. A drastic change in the electrostatic potential of the molecule involving a small geometric relaxation is found to cause this observation. PMID:26182113

  4. Comparison of the reversed passive Arthus and local Shwartzman reactions of rabbit skin: effects of the long-acting PAF antagonist UK-74,505

    PubMed Central

    Norman, Keith E; Williams, Timothy J; Rossi, Adriano G

    1997-01-01

    By using the selective, potent and long acting platelet-activating factor (PAF) antagonist, UK-74,505, we investigated the role of PAF in a local Shwartzman reaction (LSR) and a reversed passive Arthus (RPA) reaction in rabbit skin. For comparison, we also studied the effect of the PAF antagonist on neutrophil aggregation in vitro and on acute inflammatory responses induced by intradermally (i.d.) injected lipopolysaccharide (LPS), PAF, bradykinin and zymosan-activated plasma.Neutrophil aggregation was assessed photometrically. Haemorrhage, oedema formation, platelet deposition and neutrophil accumulation were quantified in rabbit skin by measuring the accumulation of i.v. injected 51Cr-labelled red blood cells (RBC), 125I-labelled human serum albumin, 111In-labelled platelets and 111In-labelled neutrophils respectively.UK-74,505 inhibited in vitro neutrophil aggregation induced by PAF but not by leukotriene B4. When injected i.v. into rabbits UK-74,505 suppressed oedema formation in response to i.d. PAF for up to 4 h but had no effect on oedema induced by bradykinin or zymosan-activated plasma.Oedema formation, but not neutrophil accumulation, produced during the RPA reaction was significantly inhibited by i.v. UK-74,505. The PAF antagonist also suppressed 111In-platelet but not 111In-neutrophil accumulation in response to i.d. LPS. UK-74,505 did not affect haemorrhage or oedema formation produced during the LPS-mediated LSR.The results demonstrate that PAF is an important mediator of oedema formation, but not neutrophil accumulation, in the immune-complex mediated RPA reaction in rabbit skin. PAF also appears to be required for platelet, but not neutrophil, accumulation in response to locally injected LPS. Our studies do not suggest a role for PAF in the LPS-mediated LSR. PMID:9105704

  5. 90Y-Labeled Anti-ROBO1 Monoclonal Antibody Exhibits Antitumor Activity against Small Cell Lung Cancer Xenografts

    PubMed Central

    Fujiwara, Kentaro; Koyama, Keitaro; Suga, Kosuke; Ikemura, Masako; Saito, Yasutaka; Hino, Akihiro; Iwanari, Hiroko; Kusano-Arai, Osamu; Mitsui, Kenichi; Kasahara, Hiroyuki; Fukayama, Masashi; Kodama, Tatsuhiko; Hamakubo, Takao; Momose, Toshimitsu

    2015-01-01

    Introduction ROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that 90Y-labeled anti-ROBO1 monoclonal antibody (90Y-anti-ROBO1 IgG) showed an antitumor effect against ROBO1-positive tumors. In this study, we performed a biodistribution study and radioimmunotherapy (RIT) against ROBO1-positive small cell lung cancer (SCLC) models. Methods For the biodistribution study, 111In-labeled anti-ROBO1 monoclonal antibody (111In-anti-ROBO1 IgG) was injected into ROBO1-positive SCLC xenograft mice via the tail vein. To evaluate antitumor effects, an RIT study was performed, and SCLC xenograft mice were treated with 90Y-anti-ROBO1 IgG. Tumor volume and body weight were periodically measured throughout the experiments. The tumors and organs of mice were then collected, and a pathological analysis was carried out. Results As a result of the biodistribution study, we observed tumor uptake of 111In-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of 111In-labeled anti-ROBO1. In the RIT study, 90Y-anti-ROBO1 IgG significantly reduced tumor volume compared with baseline. Pathological analyses of tumors revealed coagulation necrosis and fatal degeneration of tumor cells, significant reduction in the number of Ki-67-positive cells, and an increase in the number of apoptotic cells. A transient reduction of hematopoietic cells was observed in the spleen, sternum, and femur. Conclusions These results suggest that RIT with 90Y-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC. PMID:26017283

  6. Unexpected side products in the conjugation of an amine-derivatized morpholino oligomer with p-isothiocyanate benzyl DTPA and their removal.

    PubMed

    Liu, Guozheng; Dou, Shuping; Liu, Yuxia; Liang, Minmin; Chen, Ling; Cheng, Dengfeng; Greiner, Dale; Rusckowski, Mary; Hnatowich, Donald J

    2011-02-01

    In connection with pretargeting, an amine-derivatized morpholino phosphorodiamidate oligomer (NH(2)-cMORF) was conjugated conventionally with p-isothiocyanate benzyl-DTPA (p-SCN-Bn-DTPA). However, after (111)In radiolabeling, unexpected label instability was observed. To understand this instability, the NH(2)-cMORF and, as control, the native cMORF without the amine were conjugated in the conventional manner. Surprisingly, the (111)In labeling of the native cMORF conjugate was equally effective as that of the NH(2)-cMORF conjugate (>95%) despite the absence of the amine group. Furthermore, heating the radiolabeled NH(2)-cMORF and native cMORF conjugates resulted in a 35% loss and a complete loss of the label, respectively. Since the (111)In labeled DTPA is known to be stable, the instability in both cases must be due to some unstable association of DTPA to the cMORF, presumably unstable association to some endogenous sites in cMORF. Based on this assumption, a postconjugation-prepurification heating step was introduced, and labeling efficiency and stability were again investigated. By introducing the heating step, the side products were dissociated, and after purification and labeling, the NH(2)-cMORF conjugate provided a stable label and high labeling efficiency with no need for postlabeling purification. The biodistribution of this radiolabeled conjugate in normal mice showed significantly lower backgrounds compared with the labeled unstable native cMORF conjugate. In conclusion, the conventional conjugation procedure to attach the p-SCN-Bn-DTPA to NH(2)-cMORF resulted in side product(s) that were responsible for the (111)In label instability. Adding a postconjugation-prepurification heating step dissociated the side products, improved the label stability and lowered tissue backgrounds in mice. PMID:21315270

  7. Indium-111 leukocyte scintigraphic detection of myocardial abscess formation in patients with endocarditis

    SciTech Connect

    Cerqueira, M.D.; Jacobson, A.F.

    1989-05-01

    Myocardial abscess formation in patients with bacterial endocarditis in most clinical settings, especially in patients with prosthetic valves, is a primary indicator for surgical valve replacement. We report the detection of myocardial abscesses using /sup 111/In leukocyte scintigraphy in three patients with prosthetic or native valve endocarditis and nondiagnostic echocardiograms. Leukocyte scintigraphy may allow identification of myocardial abscess formation earlier than other imaging modalities.

  8. Clinical Utility of Indium 111–Labeled White Blood Cell Scintigraphy for Evaluation of Suspected Infection

    PubMed Central

    Lewis, Sarah S.; Cox, Gary M.; Stout, Jason E.

    2014-01-01

    Background  We sought to characterize the clinical utility of indium 111 (111In)–labeled white blood cell (WBC) scans by indication, to identify patient populations who might benefit most from this imaging modality. Methods  Medical records for all patients who underwent 111In-labeled WBC scans at our tertiary referral center from 2005 to 2011 were reviewed. Scan indication, results, and final diagnosis were assessed independently by 2 infectious disease physicians. Reviewers also categorized the clinical utility of each scan as helpful vs not helpful with diagnosis and/or management according to prespecified criteria. Cases for which clinical utility could not be determined were excluded from the utility assessment. Results  One hundred thirty-seven scans were included in this analysis; clinical utility could be determined in 132 (96%) cases. The annual number of scans decreased throughout the study period, from 26 in 2005 to 13 in 2011. Forty-one (30%) scans were positive, and 85 (62%) patients were ultimately determined to have an infection. Of the evaluable scans, 63 (48%) scans were deemed clinically useful. Clinical utility varied by scan indication: 111In-labeled WBC scans were more helpful for indications of osteomyelitis (35/50, 70% useful) or vascular access infection (10/15, 67% useful), and less helpful for evaluation of fever of unknown origin (12/35, 34% useful). Conclusions  111In-labeled WBC scans were useful for patient care less than half of the time at our center. Targeted ordering of these scans for indications in which they have greater utility, such as suspected osteomyelitis and vascular access infections, may optimize test utilization. PMID:25734155

  9. Ectopic Corticotropin-Producing Neuroendocrine Tumor of the Pancreas Treated With 177Lu DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy.

    PubMed

    Makis, William; McCann, Karey; Riauka, Terence A; McEwan, Alexander J B

    2016-01-01

    A 57-year-old woman diagnosed with ectopic Cushing syndrome was found to have a 111In-octreotide-avid corticotropin-producing pancreatic neuroendocrine tumor with liver metastases. She was treated with 4 induction and 4 maintenance cycles of 177Lu-DOTATATE, which normalized her serum corticotropin levels and dramatically reduced the size of the pancreatic primary and liver metastases. PMID:26359569

  10. Rapid migration of /sup 111/indium-labeled granulocytes to sites of infection

    SciTech Connect

    Dutcher, J.P.; Schiffer, C.A.; Johnston, G.S.

    1981-03-05

    Results are reported of studies with homologous, ABO-matched, /sup 111/In-labeled granulocytes given to 14 granulocytopenic patients with specific, known sites of infection. In 13 of these patients, radioactivity was noted at the site of infection after only 30 minutes. Subsequent scans at four hours or 24 hours or both were all positive at the same site. This technique provides a method for rapid diagnosis of occult infection in this patient population.

  11. Fate of gamma-interferon-activated killer blood monocytes adoptively transferred into the abdominal cavity of patients with peritoneal carcinomatosis

    SciTech Connect

    Stevenson, H.C.; Keenan, A.M.; Woodhouse, C.; Ottow, R.T.; Miller, P.; Steller, E.P.; Foon, K.A.; Abrams, P.G.; Beman, J.; Larson, S.M.

    1987-11-15

    Five patients with colorectal cancer widely metastatic to peritoneal surfaces have been treated i.p. with infusions of autologous blood monocytes made cytotoxic by in vitro incubation with human gamma-interferon. The monocytes were purified by a combination of cytapheresis and counter-current centrifugal elutriation procedures; each week approximately 350 million activated monocytes were given to patients as adoptive immunotherapy by a single i.p. instillation. On the eighth cycle of treatment the trafficking of i.p. infused blood monocytes was studied in two patients by prelabeling the cells with /sup 111/In. These activated cells became distributed widely within the peritoneal cavity. Two and 5 days after infusion their position within the peritoneum had not changed. When peritoneal specimens were obtained 36 h after /sup 111/In-labeled monocyte infusion, labeled monocytes were demonstrated to be associated with the serosal surfaces by autoradiographic analysis. Scintiscanning structures outside the abdominal cavity revealed that /sup 111/In-labeled monocytes infused i.p. did not traffic to other organs during the 5 days of the study. We conclude that i.p. adoptive transfer of autologous killer blood monocytes is an effective way of delivering these cytotoxic cells to sites of tumor burden on peritoneal surfaces in these cancer patients.

  12. Graft revascularization is essential for non-invasive monitoring of transplanted islets with radiolabeled exendin.

    PubMed

    Eter, Wael A; Bos, Desirée; Frielink, Cathelijne; Boerman, Otto C; Brom, Maarten; Gotthardt, Martin

    2015-01-01

    Islet transplantation is a novel promising strategy to cure type 1 diabetes. However, the long-term outcome is still poor, because both function and survival of the transplant decline over-time. Non-invasive imaging methods have the potential to enable monitoring of islet survival after transplantation and the effects of immunosuppressive drugs on transplantation outcome. (111)In-labeled exendin-3 is a promising tracer to visualize native and transplanted islets by SPECT (Single Photon Emission Computed Tomography). In the present study, we hypothesized that islet microvasculature plays an important role determining the uptake of exendin-3 in islets when monitoring transplant survival. We observed (111)In-exendin-3 accumulation in the transplant as early as three days after transplantation and an increase in the uptake up to three weeks post-transplantation. Islet-revascularization correlated with the increase in (111)In-exendin-3 uptake, whereas fully re-established islet vasculature coincided with a stabilized uptake of the radiotracer in the transplant. Here, we demonstrate the importance of islet vasculature for in vivo delivery of radiotracers to transplanted islets and we demonstrate that optimal and stable uptake of exendin four weeks after transplantation opens the possibility for long-term monitoring of islet survival by SPECT imaging. PMID:26490110

  13. Lipid-Calcium Phosphate Nanoparticles for Delivery to the Lymphatic System and SPECT/CT Imaging of Lymph Node Metastases

    PubMed Central

    Tseng, Yu-Cheng; Xu, Zhenghong; Guley, Kevin; Yuan, Hong; Huang, Leaf

    2014-01-01

    A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter ~25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of 111In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted 111In-LCP preferentially accumulated in the lymph nodes at ~70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only ~25% ID/g. Larger LCP (diameter ~67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected 111In-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed. PMID:24613050

  14. Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents

    SciTech Connect

    McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Roskopf, M.; Hellwig, B.

    1988-09-01

    The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included (/sup 99m/Tc)DTPA, (/sup 131/I)hippuran, (/sup 111/In)lysozyme, (/sup 99m/Tc)glucoheptonate (GHA), (/sup 99m/Tc)dimercaptosuccinate (DMS) and (/sup 111/In)aminated dextran (amdex). A small dose of (/sup 99m/Tc)- or (/sup 111/In)DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

  15. Feasibility Evaluation of Radioimmunoguided Surgery of Breast Cancer

    PubMed Central

    Ravi, Ananth; Reilly, Raymond M.; Holloway, Claire M. B.; Caldwell, Curtis B.

    2012-01-01

    Breast-conserving surgery involves completely excising the tumour while limiting the amount of normal tissue removed, which is technically challenging to achieve, especially given the limited intraoperative guidance available to the surgeon. This study evaluates the feasibility of radioimmunoguided surgery (RIGS) to guide the detection and delineation of tumours intraoperatively. The 3D point-response function of a commercial gamma-ray-detecting probe (GDP) was determined as a function of radionuclide (131I, 111In, 99mTc), energy-window threshold, and collimator length (0.0–3.0-cm). This function was used to calculate the minimum detectable tumour volumes (MDTVs) and the minimum tumour-to-background activity concentration ratio (T:B) for effective delineation of a breast tumour model. The GDP had larger MDTVs and a higher minimum required T:B for tumour delineation with 131I than with 111In or 99mTc. It was shown that for 111In there was a benefit to using a collimator length of 0.5-cm. For the model used, the minimum required T:B required for effective tumour delineation was 5.2 ± 0.4. RIGS has the potential to significantly improve the accuracy of breast-conserving surgery; however, before these benefits can be realized, novel radiopharmaceuticals need to be developed that have a higher specificity for cancerous tissue in vivo than what is currently available. PMID:22518303

  16. Graft revascularization is essential for non-invasive monitoring of transplanted islets with radiolabeled exendin

    PubMed Central

    Eter, Wael A.; Bos, Desirée; Frielink, Cathelijne; Boerman, Otto C.; Brom, Maarten; Gotthardt, Martin

    2015-01-01

    Islet transplantation is a novel promising strategy to cure type 1 diabetes. However, the long-term outcome is still poor, because both function and survival of the transplant decline over-time. Non-invasive imaging methods have the potential to enable monitoring of islet survival after transplantation and the effects of immunosuppressive drugs on transplantation outcome. 111In-labeled exendin-3 is a promising tracer to visualize native and transplanted islets by SPECT (Single Photon Emission Computed Tomography). In the present study, we hypothesized that islet microvasculature plays an important role determining the uptake of exendin-3 in islets when monitoring transplant survival. We observed 111In-exendin-3 accumulation in the transplant as early as three days after transplantation and an increase in the uptake up to three weeks post-transplantation. Islet-revascularization correlated with the increase in 111In-exendin-3 uptake, whereas fully re-established islet vasculature coincided with a stabilized uptake of the radiotracer in the transplant. Here, we demonstrate the importance of islet vasculature for in vivo delivery of radiotracers to transplanted islets and we demonstrate that optimal and stable uptake of exendin four weeks after transplantation opens the possibility for long-term monitoring of islet survival by SPECT imaging. PMID:26490110

  17. In vitro and in vivo properties of human/mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen

    SciTech Connect

    Saga, T.; Endo, K.; Koizumi, M.; Kawamura, Y.; Watanabe, Y.; Konishi, J.; Ueda, R.; Nishimura, Y.; Yokoyama, M.; Watanabe, T. )

    1990-06-01

    A human/mouse chimeric monoclonal antibody specific for a common acute lymphocytic leukemia antigen was efficiently obtained by ligating human heavy-chain enhancer element to the chimeric heavy- and light-chain genes. Cell binding and competitive inhibition assays of both radioiodine and indium-111- (111In) labeled chimeric antibodies demonstrated in vitro immunoreactivity identical with that of the parental murine monoclonal antibodies. The biodistribution of the radiolabeled chimeric antibody in tumor-bearing nude mice was similar to that of the parental murine antibody. Tumor accumulation of radioiodinated parental and chimeric antibodies was lower than that of {sup 111}In-labeled antibodies, probably because of dehalogenation of the radioiodinated antibodies. Indium-111-labeled chimeric antibody clearly visualized xenografted tumor. These results suggest that a human/mouse chimeric antibody can be labeled with {sup 111}In and radioiodine without the loss of its immunoreactivity, and that chimeric antibody localizes in vivo in the same way as the parental murine antibody.

  18. The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease

    SciTech Connect

    Teahon, K.; Smethurst, P.; Pearson, M.; Levi, A.J.; Bjarnason, I. )

    1991-07-01

    This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability (24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% {plus minus} 0.6% (mean {plus minus} SE); normal, less than 3.0%) and by high fecal excretion of 111In-labeled leukocytes (14.2% {plus minus} 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% {plus minus} 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% {plus minus} 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

  19. Autoradiographic method for quantitation of radiolabeled proteins in tissues using indium-111

    SciTech Connect

    Morrell, E.M.; Tompkins, R.G.; Fischman, A.J.; Wilkinson, R.A.; Burke, J.F.; Rubin, R.H.; Strauss, H.W.; Yarmush, M.L. )

    1989-09-01

    A quantitative autoradiographic method was developed to measure 111In-labeled proteins in extravascular tissues with a spatial resolution sufficient to associate these proteins with tissue morphology. A linear relationship between measured grain density and isotope concentration was demonstrated with uniformly-labeled standard sources of epoxy-embedded gelatin containing (111In)albumin; half-distance of spatial resolution was 0.6 micron. The technique was illustrated by measuring 24-hr accumulation of diethylenetriaminepentaacetic acid-coupled 111In-labeled human polyclonal IgG and human serum albumin (HSA) in a thigh infection model in the rat. Gamma camera images localized the infection and showed target-to-background ratios of 2.5 {plus minus} 0.3 for IgG and 1.4 {plus minus} 0.02 for human serum albumin (mean {plus minus} s.d., n = 3). Using quantitative autoradiography, significantly higher average tissue concentrations were found in the infected thighs at 4 to 4.5% of the initial plasma concentrations as compared to 0.2 to 0.3% of initial plasma concentrations in the noninfected thigh (p less than 0.05); these radiolabeled proteins were not inflammatory cell associated and localized primarily within the edematous interstitial spaces of the infection.

  20. Characterization of ZnO and Zn0.95Co0.05O prepared by sol-gel method using PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Mercurio, M. E.; Carbonari, A. W.; Cordeiro, M. R.; Saxena, R. N.

    The measurement of the electric field gradient (efg) with PAC spectroscopy was used to follow the heat treatment during the preparation of ZnO samples using sol-gel method. In particular, the investigation was carried out on samples of intrinsically n-type II-VI wurtzite semiconductor ZnO and Co-doped Zn0.95Co0.05O samples prepared by sol-gel methodology from pure metallic Zn(99.9999%). Carrier-free 111In nuclei were introduced in the samples by thermal diffusion. 111In solution was added to the precursor sol-gel solution prior to the formation of gel material. PAC measurements were carried out to follow the formation of the ZnO. Two undoped ZnO samples, which were heated in air and argon atmosphere, show different results. PAC measurements were also used to follow the 111In diffusion in a commercially purchased ZnO (99.99%) sample as well as to compare the results with the measurements taken with sol-gel prepared samples. The results show that samples prepared by sol-gel process followed by heating in argon produce better quality ZnO samples. The results also show that the Co atoms in Zn0.95Co0.05O are in substitutional sites.

  1. Characterization of ZnO and Zn0.95Co0.05O prepared by sol-gel method using PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Mercurio, M. E.; Carbonari, A. W.; Cordeiro, M. R.; Saxena, R. N.

    2007-07-01

    The measurement of the electric field gradient (efg) with PAC spectroscopy was used to follow the heat treatment during the preparation of ZnO samples using sol-gel method. In particular, the investigation was carried out on samples of intrinsically n-type II-VI wurtzite semiconductor ZnO and Co-doped Zn0.95Co0.05O samples prepared by sol-gel methodology from pure metallic Zn(99.9999%). Carrier-free 111In nuclei were introduced in the samples by thermal diffusion. 111In solution was added to the precursor sol-gel solution prior to the formation of gel material. PAC measurements were carried out to follow the formation of the ZnO. Two undoped ZnO samples, which were heated in air and argon atmosphere, show different results. PAC measurements were also used to follow the 111In diffusion in a commercially purchased ZnO (99.99%) sample as well as to compare the results with the measurements taken with sol-gel prepared samples. The results show that samples prepared by sol-gel process followed by heating in argon produce better quality ZnO samples. The results also show that the Co atoms in Zn0.95Co0.05O are in substitutional sites.

  2. Development of PEGylated Cysteine-Modified Lysine Dendrimers with Multiple Reduced Thiols To Prevent Hepatic Ischemia/Reperfusion Injury.

    PubMed

    Katsumi, Hidemasa; Nishikawa, Makiya; Hirosaki, Rikiya; Okuda, Tatsuya; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru; Sakane, Toshiyasu; Yamamoto, Akira

    2016-08-01

    To inhibit hepatic ischemia/reperfusion injury, we developed polyethylene glycol (PEG) conjugated (PEGylated) cysteine-modified lysine dendrimers with multiple reduced thiols, which function as scavengers of reactive oxygen species (ROS). Second, third, and fourth generation (K2, K3, and K4) highly branched amino acid spherical lysine dendrimers were synthesized, and cysteine (C) was conjugated to the outer layer of these lysine dendrimers to obtain K2C, K3C, and K4C dendrimers. Subsequently, PEG was reacted with the C residues of the dendrimers to obtain PEGylated dendrimers with multiple reduced thiols (K2C-PEG, K3C-PEG, and K4C-PEG). Radiolabeled K4C-PEG ((111)In-K4C-PEG) exhibited prolonged retention in the plasma, whereas (111)In-K2C-PEG and (111)In-K3C-PEG rapidly disappeared from the plasma. K4C-PEG significantly prevented the elevation of plasma alanine aminotransferase (ALT) activity, an index of hepatocyte injury, in a mouse model of hepatic ischemia/reperfusion injury. In contrast, K2C-PEG, K3C-PEG, l-cysteine, and glutathione, the latter two of which are classical reduced thiols, hardly affected the plasma ALT activity. These findings indicate that K4C-PEG with prolonged circulation time is a promising compound to inhibit hepatic ischemia/reperfusion injury. PMID:27336683

  3. Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

    SciTech Connect

    Srivastava, S.C.; Mease, R.C.; Meinken, G.E.; Mausner, L.F.; Steplewski, Z.

    1988-01-01

    High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs.

  4. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition

    SciTech Connect

    McCarthy, K.; Velchik, M.G.; Alavi, A.; Mandell, G.A.; Esterhai, J.L.; Goll, S.

    1988-06-01

    Forty-six patients (23M, 23F) ranging in age from 19 to 79 yr with a clinical history of a nonunion fracture, surgery, diabetes or a soft-tissue infection were studied with (/sup 111/In)oxine WBCs to detect osteomyelitis. There were 27 true-positive, nine true-negative, two false-positive and one false-negative. The false-positives and the false-negative occurred in patients with soft-tissue infections overlying the area of interest. All diagnoses were confirmed by intraoperative bone biopsies and cultures. Bone biopsy and scan were performed within 2 days of each other in 39 patients. The overall sensitivity was 97% (27/28), specificity, 82% (9/11) and the diagnostic accuracy, 92% (36/39). The remaining seven patients had negative (/sup 111/In)WBC scans several months after positive bone biopsies and definite antibiotic treatment. This suggests that (In)WBC scans become negative after appropriate therapy is undertaken. Interobserver data was obtained from four nuclear physicians of varying experience blinded to clinical information. A high degree of agreement was found in over 90% of the cases. This study demonstrates the utility of (/sup 111/In)WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation.

  5. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging

    SciTech Connect

    Datz, F.L.; Thorne, D.A.

    1987-05-01

    Although photon deficient defects on bone scan have received a great deal of interest, such defects in bones on Indium-111 (/sup 111/In) leukocyte imaging have not been as well recognized. We therefore undertook a retrospective review to determine the frequency and significance of such cold defects on /sup 111/In-labeled leukocyte imaging. Three hundred thirty-two scans on 290 patients were reviewed and 40 cases of decreased activity involving bone were found, for an incidence of 12%. The causes of the defects were: fracture (eight), nontraumatic avascular necrosis (eight), solid tumor (six), prostheses and other orthopedic hardware (four), advanced age (four), radiation (three), leukemia (two), osteomyelitis (two), myelofibrosis (one), postlaminectomy (one), and idiopathic (one). To determine the frequency of cold defects in osteomyelitis, all 15 cases of osteomyelitis in this series were reviewed and 12 showed increased activity, two were cold, and one was normoactive. Thus, 14% of cases of osteomyelitis presented as cold defects. We conclude that cold bone defects do occur on /sup 111/In-labeled leukocyte scans and that the causes of such defects are similar to those reported for bone and bone marrow scanning.

  6. In vivo kinetics of canine leukocytes labeled with technetium-99m HM-PAO and indium-111 tropolonate

    SciTech Connect

    Mock, B.H.; Schauwecker, D.S.; English, D.; Young, K.A.; Wellman, H.N.

    1988-07-01

    Two weeks after the introduction of osteomyelitis in three dogs, autologous leukocytes were dual-labeled with both (/sup 99m/Tc)HM-PAO and (/sup 111/In)tropolonate, and reinjected. Blood sampling and imaging were then performed. Two weeks later, the same dogs received simultaneous injections of singly-labeled (/sup 99m/Tc)WBC and (/sup 111/In)WBC for comparison. For both studies, blood samples were drawn over 6 hr to determine the respective blood clearance half-time (TB) and % recovery (%R0) of cell-bound radioactivity. There were no significant differences in the average TB results of the /sup 99m/Tc and /sup 111/In groups, either within or between the dual- and singly-labeled studies. The %R0 of singly-labeled (/sup 99m/Tc)WBC was about half that of the other groups (p less than 0.01); however, this difference was attributed to the dissimilar radiochemical purity of the (/sup 99m/Tc)HM-PAO reagents. Region of interest analysis of the 6 and 24 hr images revealed no significant differences between either cell label in the relative or absolute in vivo uptake at known sites of osteomyelitis, noninfected surgery, and normal bone marrow.

  7. Extraction, radiolabeling, and in vivo catabolism of autologous-origin equine fibrinogen and platelets in the healthy and exercise-stressed horse

    SciTech Connect

    Coyne, C.P.

    1986-01-01

    Three separate techniques were evaluated for the extraction of autologous-origin fibrinogen from whole equine plasma. Rapid extraction of equine fibrinogen with ammonium sulfate-sodium phosphate buffer, in combination with saturated glycine buffer, provided the most practical means of obtaining a protein extract with the highest degree of biological activity and sufficiently high iodine-125 (/sup 125/I) radiolabeling efficiencies using monochloroiodine reagent (ICI). A technique was developed for the in vitro radiolabeling of equine platelets suspended in plasma. This entailed the use of the isotope, indium-111 (/sup 111/In), together with the lipophilic ligand, 2-(mercaptopyridine-N-oxide). This labeling technique achieved labeling efficiencies between 75% and 96%, and in vitro aggregability of /sup 111/In-merc radiolabeled platelets was comparable to that of unlabeled cell isolates. In the final phase of the investigation, autologous-origin /sup 125/I-labeled fibrinogen and /sup 111/In-labeled platelets were applied in a series of equine exercise physiology studies. Elimination of these two radiobiologicals was evaluated in the resting and exercise-stressed horse. Results from these investigations revealed no long-term influence of exercise conditioning on the in vivo kinetics of radiolabeled fibrinogen or platelets.

  8. Annexin A5-Functionalized Nanoparticle for Multimodal Imaging of Cell Death

    PubMed Central

    Zhang, Rui; Huang, Miao; Zhou, Min; Wen, Xiaoxia; Huang, Qian; Li, Chun

    2013-01-01

    Techniques for visualizing cell death can provide noninvasive assessment of both disease states and response to therapeutic intervention. The purpose of this study was to develop and evaluate a multimodal imaging nanoplatform for the detection of cell death. Method In this study, we evaluated 111In-labeled Annexin A5-conjugated core-crosslinked polymeric micelles (CCPM) for multimodal imaging of cell death in various disease models. Three different models were conducted, including tumor apoptosis, hepatic apoptosis and inflammation. Both micro-single photon emission tomography/computed tomography (µSPECT/CT) and fluorescence molecular tomography (FMT) were performed. Biodistribution and immunohistochemistry assays were carried out to validate selectivity of cell death imaging. Result In all disease models, cell death was clearly visualized by both µSPECT/CT and FMT. In contrast, there was relatively low signal in the corresponding tissues of control mice. Moreover, the radioactive signal from 111In-labeled annexin A5-CCPM colocalized with its fluorescence signal, and both signals were confined to regions of dying cells. Conclusion 111In-labeled annexin A5-CCPM allows visualization of cell death by both nuclear and optical techniques at whole-body level as well as at microscopic level. It has the potential to aid diagnosis of disease states or tissue responses involving abnormal cell death. PMID:23490444

  9. Fluorescence-enhanced europium complexes for the assessment of renal function

    NASA Astrophysics Data System (ADS)

    Chinen, Lori K.; Galen, Karen P.; Kuan, K. T.; Dyszlewski, Mary E.; Ozaki, Hiroaki; Sawai, Hiroaki; Pandurangi, Raghootama S.; Jacobs, Frederick G.; Dorshow, Richard B.; Rajagopalan, Raghavan

    2008-02-01

    Real-time, non-invasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu 3+ complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via the intramolecular ligand-metal fluorescence resonance energy transfer (FRET) process. The results show that Eu-DTPA-monoamide complex 13a, which contains a quinoxanlinyl antenna, exhibits large (c.a. 2700-fold) Eu 3+ fluorescence enhancement over Eu-DTPA (4c). Indeed, complex 13a exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance profile of the corresponding radioactive 111In complex 13c is similar to that of 111In-DTPA, albeit 13c clears slower than 111In-DTPA. The biodistribution data indicates that 13c, and, by inference, 13a clear via a complex mechanism that includes glomerular filtration.

  10. From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

    PubMed Central

    Pawlak, Dariusz; Rangger, Christine; Peitl, Petra Kolenc; Garnuszek, Piotr; Maurin, Michał; Ihli, Laura; Kroselj, Marko; Maina, Theodosia; Maecke, Helmut; Erba, Paola; Kremser, Leopold; Hubalewska-Dydejczyk, Alicja; Mikołajczak, Renata; Decristoforo, Clemens

    2016-01-01

    Introduction A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA–DGlu–DGlu–DGlu–DGlu–DGlu–DGlu– Ala–Tyr–Gly–Trp–Met–Asp–Phe–NH2 (CP04) after labelling with 111In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze-dried formulation of the precursor CP04 for a first multi-centre clinical trial with 111In-CP04 in MTC patients. Materials and methods The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 μg) were prepared and radiolabelled with 111In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. Results Use of ascorbic acid buffer (pH 4.5) allowed freeze-drying of the kit formulation with satisfactory pellet-formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met11-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 μg formulation. The final formulations contained 10 or 50 μg CP04, 25 mg ascorbic acid, 0.5 mg gentisic acid and 5 mg l-methionine. The radiolabelling performed by incubation of 200–250 MBq 111InCl3 at 90 °C for 15 min resulted in reproducible radiochemical purity (RCP) >94%. Kit-stability was proven for >6

  11. Effect of tumor mass and antigenic nature on the biodistribution of labeled monoclonal antibodies in mice

    SciTech Connect

    Watanabe, Y.; Endo, K.; Koizumi, M.; Kawamura, Y.; Saga, T.; Sakahara, H.; Kuroki, M.; Matsuoka, Y.; Konishi, J.

    1989-06-01

    The effect of tumor mass and antigenic nature on the biodistribution of 111In- and 125I-labeled monoclonal antibodies (MoAbs) was studied using F(ab')2 fragments of three representative anti-tumor MoAbs and SW1116 human colorectal carcinoma grown in nude mice. The 19-9, F33-104 anti-CEA, and 17-1A MoAbs showed specific binding to SW1116 cells. The former two MoAbs recognize circulating CA 19-9 with molecular weights of more than 5,000,000 and CEA of Mr 170,000-180,000, respectively, whereas 17-1A reacts with a nonshedding antigen. Both percentage injected dose per gram tumor and tumor-to-blood ratios were inversely proportional to the tumor mass in nude mice administered 111In- and 125I-labeled 19-9, but liver uptake increased as tumor size increased. Analysis of serum samples and tumor homogenates demonstrated the presence of a high-molecular-weight species, probably due to the antibody binding to CA 19-9. In the case of 111In-labeled anti-CEA MoAb, tumor uptake also decreased and liver uptake increased with tumor size, but this effect was less obvious than that of 19-9. In contrast, tumor and liver uptake of 125I-labeled anti-CEA MoAb, 111In- and 125I-labeled 17-1A and control antibodies were independent of tumor mass. The absolute tumor uptake and tumor-to-blood ratios of all 125I-labeled antibodies were lower than those of the 111In-labeled ones. And the effect of tumor mass was also weaker with 125I-labeled antibodies, probably due to in vivo dehalogenation. These results indicate that the effect of tumor size on the incorporation of labeled MoAb into tumors is dependent on the antigenic nature to be targeted and/or radionuclides used for labeling and that high concentrations of circulating high molecular weight antigens may limit in vivo use of MoAb conjugates.

  12. Radiolabeled Antibodies in Prostate Cancer: A Case Study Showing the Effect of Host Immunity on Antibody Bio-distribution

    PubMed Central

    Vilhelmsson-Timmermand, Oskar; Santos, Elmer; Thorek, Daniel LJ; Evans-Axelsson, Susan; Bjartell, Anders; Lilja, Hans; Larson, Steven M; Strand, Sven-Erik; Tran, Thuy A.; Ulmert, David

    2015-01-01

    Objectives Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissimilarity in bio-distribution of 111In-DTPA-5A10, which targets free Prostate Specific Antigen (fPSA), in two animal models. Methods In vivo bio-distribution studies of 111In-DTPA-5A10 were performed in immunodeficient BALB/c-nu or NMRI-nu mice with subcutaneous (s.c.) LNCaP tumors. Targeting-specificity of the tracer was assessed by quantifying the uptake in (a) mice with s.c. xenografts of PSA-negative DU145 cells as well as (b) BALB/c-nu or NMRI-nu mice co-injected with an excess of non-labeled 5A10. Finally, the effect of neonatal Fc-receptor (FcRn) inhibition on the bio-distribution of the conjugate was studied by saturating FcRn-binding capacity with nonspecific IgG1. Results The inherent biological attributes of the mouse model substantially influenced the bio-distribution and pharmacokinetics of 111In-DTPA-5A10. With LNCaP xenografts in BALB/c-nu mice (with intact B and NK cells but with deficient T cells) versus NMRI-nu mice (with intact B cells, increased NK cells and absent T cells), we observed a significantly higher hepatic accumulation (26±3.9 versus 3.5±0.4 %IA/g respectively), and concomitantly lower tumor uptake (25±11 versus 52±10 %IA/g respectively) in BALB/c-nu mice. Inhibiting FcRn by administration of nonspecific IgG1 just prior to 111In-DTPA-5A10 did not change tumor accumulation significantly. Conclusions We demonstrated that the choice of immunodeficient mouse model importantly influence the bio-distribution of 111In-DTPA-5A10. This study further highlighted important considerations in the evaluation of preclinical tracers, with

  13. Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies.

    SciTech Connect

    Shen, Shang; Forero, Andres; LoBuglio, Albert F.; Breitz, H; Khazaeli, M B.; Fisher, Darrell R.; Wang, W Q.; Meredith, Ruby F.

    2005-04-01

    Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor (90)Y doses were calculated based on (111)In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. RESULTS: The (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean (90)Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body

  14. (R)-NODAGA-PSMA: A Versatile Precursor for Radiometal Labeling and Nuclear Imaging of PSMA-Positive Tumors

    PubMed Central

    Gourni, Eleni; Canovas, Coline; Goncalves, Victor; Denat, Franck; Meyer, Philipp T.; Maecke, Helmut R.

    2015-01-01

    Purpose The present study aims at developing and evaluating an urea-based prostate specific membrane antigen (PSMA) inhibitor suitable for labeling with 111In for SPECT and intraoperative applications as well as 68Ga and 64Cu for PET imaging. Methods The PSMA-based inhibitor-lysine-urea-glutamate-coupled to the spacer Phe-Phe-D-Lys(suberoyl) and functionalized with the enantiomerically pure prochelator (R)-1-(1-carboxy-3-carbotertbutoxypropyl)-4,7-carbotartbutoxymethyl)-1,4,7-triazacyclononane ((R)-NODAGA(tBu)3), to obtain (R)-NODAGA-Phe-Phe-D-Lys(suberoyl)-Lys-urea-Glu (CC34). CC34 was labeled with 111In, 68Ga and 64Cu. The radioconjugates were further evaluated in vitro and in vivo in LNCaP xenografts by biodistribution and PET studies. Biodistribution studies were also performed with 68Ga-HBED-CC-PSMA (HBED-CC: N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid) and 111In-PSMA-617 for comparison. Results 68Ga-CC34, 64Cu-CC34, and 111In-CC34 were prepared in radiochemical purity >95%. 68/natGa-CC34, 64/natCu-CC34, 111/natIn-CC34, 68/natGa-HBED-CC-PSMA, and 111/natIn-PSMA-617 exhibited high affinity for the LNCaP cells, with Kd values of 19.3±2.5 nM, 27.5±2.7 nM, 5.5±0.9 nM, 2.9±0.6 nM and 5.4±0.8 nM, respectively. They revealed comparable internalization profiles with approximately 75% of the total cell associated activity internalized after 3 h of incubation. 68Ga-CC34 showed very high stability after its administration in mice. Tumor uptake of 68Ga-CC34 (14.5±2.9% IA/g) in LNCaP xenografts at 1 h p.i. was comparable to 68Ga-HBED-CC-PSMA (15.8±1.4% IA/g) (P = 0.67). The tumor-to-normal tissue ratios at 1 and 2 h p.i of 68Ga-CC34 were also comparable to 68Ga-HBED-CC-PSMA (P>0.05). Tumor uptake of 111In-CC34 (28.5±2.6% IA/g) at 1 h p.i. was lower than 111In-PSMA-617 (52.1±6.5% IA/g) (P = 0.02). The acquisition of PET-images with 64Cu-CC34 at later time points showed wash-out from the kidneys, while tumor uptake still remained

  15. Magnetic and Structural Properties of LANTHANUM(2-X) Strontium(x) Copper OXYGEN(4+DELTA) Studied with Time - Perturbed Angular Correlations

    NASA Astrophysics Data System (ADS)

    Saylor, Janet Marie

    Structural and magnetic properties of the high temperature superconductor La_{2-x}Sr_{x} CuO_{4-y} have been studied with ^{111} In/^{111}Cd perturbed angular gammagamma-correlations (PAC). In these measurements ppm of the radioactive probe, ^{111}In, is diffused into small samples by heat treatment. During the 2.8 day half-life of ^{111}In, the hyperfine spectrum of the I = 5/2, 85 ns. excited state of ^{111}Cd can be studied. A number of complex combined magnetic-dipole -electric-quadrupole interactions are observed. These depend simply on the sample preparation which controls the types and concentration of oxygen defects which exist in the sample. In particular, we have found that vacuum annealing results in a unique PAC spectrum. In this case, which only occurs when the samples are nearly exactly oxygen stoichiometric, the ^{111}Cd probe sits at the La site with no oxygen defects nearby. The principle axis of the electric field gradient ( omega_{o} = 240 Mrad/s) is found to be nearly parallel to the tetragonal c-axis and perpendicular to the hyperfine field ( omega_{L} = 10 Mrad/s). The temperature dependence and orientation of the hyperfine field, the electric field gradient and its asymmetry parameter (eta~ 0.1) have been studied for lightly doped La_{2-x }Sr_{x}CuO _4. We found first that hyperfine field is proportional to bulk magnetization, and second that eta is proportional orthorhombic distortion (To = 530 K). This unique sensitivity of our probe to both the magnetic and structural phase transitions in La _2CuO_{4+delta }, combined with the microscopic information on oxygen stoichiometry it can provide, have made ^{111}In/^{111 }Cd PAC ideal for studies of complex phase diagram of La_{2-x}Sr _{x}CuO _4. Results from these investigations include the first microscopic determination of the oxygen stoichiometry of La_{2-x}Sr _{x}CuO _4 and observation of the maximum Neel temperature; measurement of the magnetic critical exponent, beta = 0.50(4), and the

  16. Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

    PubMed Central

    2013-01-01

    Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well as registration accuracy between SPECT and CT can be influenced by several factors. Here we investigate how such inaccuracies influence micro-SPECT quantification. Methods Effects of (1) misalignments between micro-SPECT and micro-CT through shifts and rotation, (2) globally altered attenuation coefficients and (3) combinations of these were evaluated. Tests were performed with a NEMA NU 4–2008 phantom and with rat cadavers containing sources with known activity. Results Changes in measured activities within volumes of interest in phantom images ranged from <1.5% (125I) and <0.6% (201Tl, 99mTc and 111In) for 1-mm shifts to <4.5% (125I) and <1.7% (201Tl, 99mTc and 111In) with large misregistration (3 mm). Changes induced by 15° rotation were smaller than those by 3-mm shifts. By significantly altering attenuation coefficients (±10%), activity changes of <5.2% for 125I and <2.7% for 201Tl, 99mTc and 111In were induced. Similar trends were seen in rat studies. Conclusions While getting sufficient accuracy of attenuation maps in clinical imaging is highly challenging, our results indicate that micro-SPECT quantification is quite robust to various imperfections of attenuation maps. PMID:23369630

  17. In vivo characterization of the novel CD44v6-targeting Fab fragment AbD15179 for molecular imaging of squamous cell carcinoma: a dual-isotope study

    PubMed Central

    2014-01-01

    Background Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties to detect small tumours and metastases. Imaging methods available are not sufficient, and radio-immunodiagnostics could increase specificity and sensitivity of diagnostics. The objective of this study was to evaluate, for the first time, the in vivo properties of the radiolabelled CD44v6-targeting fragment AbD15179 and to assess its utility as a targeting agent for radio-immunodiagnostics of CD44v6-expressing tumours. Methods The fully human CD44v6-targeting Fab fragment AbD15179 was labelled with 111In or 125I, as models for radionuclides suitable for imaging with SPECT or PET. Species specificity, antigen specificity and internalization properties were first assessed in vitro. In vivo specificity and biodistribution were then evaluated in tumour-bearing mice using a dual-tumour and dual-isotope setup. Results Both species-specific and antigen-specific binding of the conjugates were demonstrated in vitro, with no detectable internalization. The in vivo studies demonstrated specific tumour binding and favourable tumour targeting properties for both conjugates, albeit with higher tumour uptake, slower tumour dissociation, higher tumour-to-blood ratio and higher CD44v6 sensitivity for the 111In-labelled fragment. In contrast, the 125I-Fab demonstrated more favourable tumour-to-organ ratios for liver, spleen and kidneys. Conclusions We conclude that AbD15179 efficiently targets CD44v6-expressing squamous cell carcinoma xenografts, and particularly, the 111In-Fab displayed high and specific tumour uptake. CD44v6 emerges as a suitable target for radio-immunodiagnostics, and a fully human antibody fragment such as AbD15179 can enable further clinical imaging studies. PMID:24598405

  18. Relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons

    SciTech Connect

    Savage, B.; McFadden, P.R.; Hanson, S.R.; Harker, L.A.

    1986-08-01

    The relationship between platelet density and platelet age has been studied using continuous linear Percoll density gradients and 111In-labeling of autologous platelets in baboons. To investigate changes in platelet density during senescence in the circulation, baboons were infused with 111In-labeled autologous platelets, and blood was collected at one hour postinfusion and twice daily thereafter for six days. Platelets were isolated from these samples in high yield (greater than 95%) and separated in continuous linear Percoll density gradients following density equilibrium centrifugation. Although at one hour postinfusion the density distribution of radiolabeled platelets coincided closely with the distribution of the total platelet population, a detectable symmetrical shift toward higher densities was observed after five days. The relative specific radioactivity (RSR) of high-density platelets (1.064 to 1.067 g/mL) decreased at a slower rate than that of the total platelet population (platelets of all densities), whereas the RSR of low-density platelets (1.053 to 1.056 g/mL) showed a more immediate and rapid decrease. These results give rise to one of two interpretations: (1) low-density platelets have a shorter survival time than more dense platelets and are therefore cleared from the circulation at a faster rate, or (2) platelets of all densities increase in density upon aging in the circulation. To determine the explanation for changing RSR of different density fractions we studied the in vivo disappearance characteristics of low- and high-density 111In-labeled platelets. There were no significant differences between the mean survival times of low-density platelets (5.0 +/- 0.49 days, +/- 1 SD, n = 6), high-density platelets (4.9 +/- 0.56 days, n = 6), or control platelets representing platelets of all densities (4.9 +/- 0.38 days, n = 6).

  19. Thromboembolic potential of synthetic vascular grafts in baboons

    SciTech Connect

    Schneider, P.A.; Kotze, H.F.; Heyns, A.D.; Hanson, S.R.

    1989-07-01

    We have compared in baboons the capacity of two types of synthetic vascular grafts to accumulate thrombus, activate circulating platelets, and generate occlusive platelet microemboli. Grafts were incorporated into femoral arterial-arterial shunts placed unilaterally in 10 baboons; the unoperated contralateral limbs served as controls. The accumulation of indium 111 (111In)-labeled platelets onto the grafts (expanded polytetrafluoroethylene (ePTFE) or knitted Dacron, 4 mm inner diameter) and the appearance of 111In radioactivity in distal microcirculatory beds (calf and foot) were quantified by dynamic scintillation camera imaging. After 1 hour total platelet deposition per graft was higher with Dacron (49.0 +/- 8.0 x 10(9) platelets) than with ePTFE (3.7 +/- 0.6 x 10(9) platelets, p less than 0.01). Platelet counts decreased and beta-thromboglobulin levels increased with Dacron graft placement but were unaffected by ePTFE graft placement (p less than 0.05 and p less than 0.01, respectively). Emboli shed from Dacron grafts were detected as multifocal, irregular, and changing deposits in the calves and feet. Indium 111 platelet activity in the feet distal to the Dacron grafts increased 81.1% +/- 21.4% from baseline values over 1 hour, whereas the activities in the feet distal to the ePTFE grafts were unchanged (p less than 0.05). The increase 111In-platelet radioactivity above the control limb values (excess radioactivity) was higher for the Dacron graft group than for the ePTFE group in both the feet (139.6% +/- 46.9% vs 6.2%, p less than 0.05) and the calves (86.7% +/- 21.7% vs 7.3% +/- 3.6%, p less than 0.05).

  20. Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma

    SciTech Connect

    Sandrock, D.; Blossey, H.C.; Steinroeder, M.; Munz, D.L.

    1989-01-01

    We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG.

  1. Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging.

    PubMed

    Kanazaki, Kengo; Sano, Kohei; Makino, Akira; Yamauchi, Fumio; Takahashi, Atsushi; Homma, Tsutomu; Ono, Masahiro; Saji, Hideo

    2016-03-28

    Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG ((111)In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5-40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method ((111)In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using (111)In-DTPA-PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging. PMID:26869546

  2. Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA-peptide in tumor-bearing mice

    SciTech Connect

    DeNardo, S.J.; Zhong, G.R.; Salako, Q.

    1995-05-01

    A bifunctional chelating agent, DOTA-Gly{sub 3}-L-(p-isothiocyanato)-phenylalanine amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer xenografts (HBT 3477) to determine its potential for radioimmunoconjugate therapy. Indium-111 and yttrium-90 were attached to an anti-adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by purification. The unique characteristic of the DOTA-peptide-NCS to form neutral complexes with trivalent metals was utilized to separate the resulting {sup 111}In and {sup 90}Y radiochelates from excess chelating agent and other anionic by-products resulting from metal impurities. The purified radiochelates were then conjugated to ChL6. The paramacokinetics of {sup 111}In- and {sup 90}Y-DOTA-peptide-ChL6 were obtained for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results were compared with the pharmacokinetics of {sup 125}I-ChL6 obtained in the same mouse model. The whole-body clearance of {sup 125}I-ChL6, {sup 90}Y-and {sup 111}In-DOTA-peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr, respectively. Blood clearances of the three radiopharmaceuticals were biphasic. The radiometal immunoconjugates had greater tumor uptake and slower clearances. Indium-111- and {sup 90}Y-DOTA-peptide-ChL6 can be produced at high specific activity with fewer than one chelate per MAb by using a pre-labeling method that permits radiochelate purification by charge selection. Studies in mouse xenografts indicate that tumor uptake in enhanced and a favorable therapeutic index is achieved using these agents. 29 refs., 7 figs., 2 tabs.

  3. The mechanism of hepatic uptake of a radiolabelled monoclonal antibody.

    PubMed

    Boyle, C C; Paine, A J; Mather, S J

    1992-04-01

    Clinical and experimental scintigraphic studies have found that radiolabelled antibodies are not only taken up by tumour(s) but also by normal liver. The accumulation of radionuclides in this organ poses a major problem to the use of radiolabelled antibodies as diagnostic and therapeutic tools. In an attempt to understand the mechanism of hepatic uptake and clearance of radiolabelled antibodies, the intrahepatic biodistribution of an 111In-labelled MAb (HMFG1), was determined following i.v. administration to normal male rats. Two hours after administration the liver contained 15% of the injected dose, with most of the remaining radioactivity in the blood. The hepatic burden of the 111In MAb remained constant over the next 72 hr in the face of decreasing blood levels of radioactivity as well as its urinary and faecal excretion. At 2 and 72 hr after injection, 50% and 10% respectively of the hepatic radiolabel was due to blood borne antibody. Following a collagenase-cell isolation procedure, only 23% of the amount remaining in the liver at 2 hr was found to be cell-associated; 66% was lost during the cell isolation and purification procedure. Cellular uptake increased with time so that, by 72 hr after administration, 58% was cell-associated and 29% freely removable. At all timepoints, the parenchymal cells contained more activity than non-parenchymal cells. No evidence of antibody-receptor interactions could be obtained either in vivo or in cultures of hepatic parenchymal and non-parenchymal cells. Our data suggest that the bulk of the hepatic burden of 111In MAb results from extravascular pooling of the antibody. PMID:1555890

  4. Diffuse nesidioblastosis with hypoglycemia mimicking an insulinoma: a case report

    PubMed Central

    2012-01-01

    Introduction We describe a case of diffuse nesidioblastosis in an adult patient who presented with exclusively fasting symptoms and a focal pancreatic 111In-pentetreotide uptake mimicking an insulinoma. Case presentation A 23-year-old Caucasian man had severe daily fasting hypoglycemia with glucose levels below 2mmol/L. Besides rare neuroglycopenic symptoms (confusion, sleepiness), he was largely asymptomatic. His investigations revealed low venous plasma glucose levels, high insulin and C-peptide levels and a 72-hour fast test that were all highly suggestive for an insulinoma. Abdominal computed tomography and magnetic resonance imaging did not reveal any lesions. The sole imagery that was compatible with an insulinoma was a 111In-somatostatin receptor scintigraphy that showed a faint but definite focal tracer between the head and the body of the pancreas. However, this lesion could not be confirmed by endoscopic ultrasonography of the pancreas. Following duodenopancreatectomy, the histological findings were consistent with diffuse nesidioblastosis. Postoperatively, the patient continued to present with fasting hypoglycemia and was successfully treated with diazoxide. Conclusion In the absence of gastrointestinal surgery, nesidioblastosis is very rare in adults. In addition, nesidioblastosis is usually characterized by post-prandial hypoglycemia, whereas this patient presented with fasting hypoglycemia. This case also illustrates the risk for a false positive result of 111In-pentetreotide scintigraphy in the case of nesidioblastosis. Selective arterial calcium stimulation and venous sampling is the most reliable procedure for the positive diagnosis of insulinoma or nesidioblastosis and should be used to confirm any suspicion based on imaging modalities. PMID:23031644

  5. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  6. Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration.

    PubMed

    Patel, Aateka; Woods, A; Riffo-Vasquez, Yanira; Babin-Morgan, Anna; Jones, Marie-Christine; Jones, Stuart; Sunassee, Kavitha; Clark, Stephen; T M de Rosales, Rafael; Page, Clive; Spina, Domenico; Forbes, Ben; Dailey, Lea Ann

    2016-08-10

    Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5±0.9h (R(2)=0.995) and 10.6±0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation. PMID:27180635

  7. Clinical comparison of indium-111 acetylacetone and indium-111 tropolone granulocytes

    SciTech Connect

    Schauwecker, D.S.; Burt, R.W.; Park, H.M.; Mock, B.H.; Witt, R.M.; Tobolski, M.M.; Wellman, H.N.

    1986-11-01

    This clinical study compares the efficacy of two /sup 111/In white blood cells preparations. Seventy-six patients were imaged after an injection of granulocytes (GRAN) isolated on a Ficoll-Hypaque gradient and labeled with (/sup 111/In)acetylacetone (ACAC) in saline; 105 patients were imaged after an injection of GRAN isolated on a metrizamide-plasma gradient and labeled with (/sup 111/In)tropolone (TROP) in plasma. Early (2-4 hr), intermediate (4-6 hr), and delayed (24 hr) images were obtained. The specificity was quite high (94-100%) in both preparations and no statistical differences could be found. The sensitivity for ACAC-GRAN for the early, intermediate, and delayed images were 39%, 63%, and 64%, respectively; for TROP-GRAN it was 80%, 89%, and 92%, respectively. In all cases the TROP-GRAN images were significantly more sensitive than the ACAC-GRAN images obtained at the same time after injection (p less than 0.001 for early and delayed images, 0.01 less than p less than 0.025 for intermediate images). For ACAC-GRAN the intermediate and delayed images were significantly more sensitive than the early images, while no significant difference could be found for TROP-GRAN. In a blinded experiment, the ability of TROP-GRAN to demonstrate a lesion was compared to that of ACAC-GRAN. TROP-GRAN demonstrated the lesions better than ACAC-GRAN, both in the early and late images (p less than 0.001). TROP-GRAN visualization scores at 4-6 hr equaled those obtained 24 hr after injection. In conclusion, GRAN separated and labeled in plasma with TROP are superior to those separated and labeled in saline with ACAC in three ways: higher visualization scores, earlier visualization of the lesion, and greater sensitivity.

  8. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  9. A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

    PubMed Central

    Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Azad, Babak Behnam; Pomper, Martin G.; Nimmagadda, Sridhar

    2016-01-01

    Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID:26848870

  10. Spectral functions of isolated Ce adatoms on paramagnetic surfaces.

    PubMed

    Gardonio, S; Wehling, T O; Petaccia, L; Lizzit, S; Vilmercati, P; Goldoni, A; Karolak, M; Lichtenstein, A I; Carbone, C

    2011-07-01

    We report photoemission experiments revealing the full valence electron spectral function of Ce adatoms on Ag(111), W(110), and Rh(111) surfaces. A transfer of Ce 4f spectral weight from the ionization peak towards the Fermi level is demonstrated upon changing the substrate from Ag(111) to Rh(111). In the intermediate case of Ce on W(110) the ionization peak is found to be split. This evolution of the spectra is explained by means of first-principles theory, which clearly demonstrates that a reliable understanding of magnetic adatoms on metal surfaces requires simultaneous low and high energy spectroscopic information. PMID:21797632

  11. Radionuclide evaluation of renal transplants

    SciTech Connect

    Dubovsky, E.V.; Russell, C.D.

    1988-07-01

    In this review article, the following topics are treated: the radiopharmaceuticals /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA), /sup 131/I-orthoiodohippurate (OIH), /sup 99m/Tc-mercaptoacetyltriglycine (MAG3), /sup 67/Ga-citrate, radioiodinated fibrinogen, /sup 99m/Tc-sulfur colloid, 111In-labelled white cells and platelets; gamma camera methods based on images, on first pass and on tubular transit; blood clearance methods; and the diagnosis of surgical complications, acute rejection (AR), acute tubular necrosis (ATN), chronic rejection (CR), and cyclosporine-A (CYA) toxicity. 94 references.

  12. Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

    SciTech Connect

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.; Adams, M.B.; Isitman, A.T.; Hellman, R.S.; Hoffmann, R.G.; Rao, S.A.; Joestgen, T.; Krohn, L.

    1986-08-01

    A prospective evaluation of /sup 111/In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined (/sup 99m/Tc)DTPA and (/sup 131/I)orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival.

  13. Fluctuating Electric Field Gradients at 111Cd in Ice

    NASA Astrophysics Data System (ADS)

    Akselrod, Z. Z.; Filossofov, D. V.; Kochetov, O. I.; Korolev, N. A.; Lebedev, N. A.; Milanov, M.; Novgorodov, A. F.; Shirani, E. N.; Timkin, V. V.; Velichkov, A. I.

    2001-11-01

    111Cd PAC measurements have been made using the high specific activity of 111In in the methanol water mixtures of various concentrations at the room temperature. These experiments revealed that the perturbation factors (integrated over two mean lives τN) do not follow the dependence of the macroscopic viscosity η. The observed dynamic character of the PAC spectra in ice is explained by the mobility of orientational and ionic defects. The activation energy for the diffusion process was determined to be E a =0.35(1) eV.

  14. Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules.

    PubMed

    Ahlgren, Sara; Orlova, Anna; Rosik, Daniel; Sandström, Mattias; Sjöberg, Anna; Baastrup, Barbro; Widmark, Olof; Fant, Gunilla; Feldwisch, Joachim; Tolmachev, Vladimir

    2008-01-01

    Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i. PMID:18163536

  15. Cloning of cDNA encoding human rapsyn and mapping of the RAPSN gene locus to chromosome 11p11.2-p11.1

    SciTech Connect

    Buckel, A.; Beeson, D.; Vincent, A.

    1996-08-01

    We have isolated and sequenced cDNA clones for the human 43-kDa acetylcholine receptor-associated protein rapsyn. The cDNA encodes a 412-amino-acid protein that has a predicted molecular mass of 46,330 Da and shows 96% sequence identity with mouse rapsyn. Analysis of PCR amplifications, first from somatic cell hybrids and subsequently from radiation hybrids, localizes the human RAPSN gene locus to chromosome 11p11.2-p11.1 in close proximity to ACP2. 12 refs., 2 figs.

  16. A high performance hybrid battery based on aluminum anode and LiFePO4 cathode

    DOE PAGESBeta

    Sun, Xiao-Guang; Bi, Zhonghe; Liu, Hansan; Bridges, Craig A.; Paranthaman, Mariappan Parans; Dai, Sheng; Brown, Gilbert M.

    2015-12-07

    A unique battery hybrid utilizes an aluminum anode, a LiFePO4 cathode and an acidic ionic liquid electrolyte based on 1-ethyl-3-methylimidazolium chloride (EMImCl) and aluminum trichloride (AlCl 3) (EMImCl-AlCl 3, 1-1.1 in molar ratio) with or without LiAlCl4 is proposed. This hybrid ion battery delivers an initial high capacity of 160 mAh g-1 at a current rate of C/5. It also shows good rate capability and cycling performance.

  17. Layer-Resolved Evolution of Organic Thin Films Monitored by Photoelectron Emission Microscopy and Optical Reflectance Spectroscopy

    PubMed Central

    2015-01-01

    Photoelectron emission microscopy (PEEM) and differential (optical) reflectance spectroscopy (DRS) have proven independently to be versatile analytical tools for monitoring the evolution of organic thin films during growth. In this paper, we present the first experiment in which both techniques have been applied simultaneously and synchronously. We illustrate how the combined PEEM and DRS results can be correlated to obtain an extended perspective on the electronic and optical properties of a molecular film dependent on the film thickness and morphology. As an example, we studied the deposition of the organic molecule α-sexithiophene on Ag(111) in the thickness range from submonolayers up to several monolayers. PMID:26523159

  18. Transverse field muon-spin rotation measurement of the topological anomaly in a thin film of MnSi

    NASA Astrophysics Data System (ADS)

    Lancaster, T.; Xiao, F.; Salman, Z.; Thomas, I. O.; Blundell, S. J.; Pratt, F. L.; Clark, S. J.; Prokscha, T.; Suter, A.; Zhang, S. L.; Baker, A. A.; Hesjedal, T.

    2016-04-01

    We present the results of transverse-field muon-spin rotation measurements on an epitaxially grown 40-nm-thick film of MnSi on Si(111) in the region of the field-temperature phase diagram where a skyrmion phase has been observed in the bulk. We identify changes in the quasistatic magnetic field distribution sampled by the muon, along with evidence for magnetic transitions around T ≈40 and 30 K. Our results suggest that the cone phase is not the only magnetic texture realized in film samples for out-of-plane fields.

  19. Competing Forces during Contact Formation between a Tip and a Single Molecule.

    PubMed

    Caffrey, Nuala M; Buchmann, Kristof; Hauptmann, Nadine; Lazo, Cesar; Ferriani, Paolo; Heinze, Stefan; Berndt, Richard

    2015-08-12

    Sn-phthalocyanine adsorbs on Ag(111) in a physisorbed or a chemisorbed configuration. Both structures are contacted with the tip of a combined scanning tunneling and atomic force microscope. The tunneling conductances of both configurations exhibit similar exponential variations with the tip-molecule distance. The short-range forces, however, display nontrivial distance dependencies. First-principles calculations reproduce the experimental results. Both attractive and repulsive interactions occur between the tip and different parts of the molecule due to a combination of bond formation and electrostatic interactions with the tip electric dipole. Consequently, deformations occur and the force varies in the resulting unexpected fashion. PMID:26218345

  20. Selection of optimal chelator improves the contrast of GRPR imaging using bombesin analogue RM26.

    PubMed

    Mitran, Bogdan; Varasteh, Zohreh; Selvaraju, Ram Kumar; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Tolmachev, Vladimir; Rosenström, Ulrika; Orlova, Anna

    2016-05-01

    Bombesin (BN) analogs bind with high affinity to gastrin-releasing peptide receptors (GRPRs) that are up-regulated in prostate cancer and can be used for the visualization of prostate cancer. The aim of this study was to investigate the influence of radionuclide-chelator complexes on the biodistribution pattern of the 111In-labeled bombesin antagonist PEG2-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (PEG2-RM26) and to identify an optimal construct for SPECT imaging. A series of RM26 analogs N-terminally conjugated with NOTA, NODAGA, DOTA and DOTAGA via a PEG2 spacer were radiolabeled with 111In and evaluated both in vitro and in vivo. The conjugates were successfully labeled with 111In with 100% purity and retained binding specificity to GRPR and high stability. The cellular processing of all compounds was characterized by slow internalization. The IC50 values were in the low nanomolar range, with lower IC50 values for positively charged natIn-NOTA-PEG2-RM26 (2.6 ± 0.1 nM) and higher values for negatively charged natIn-DOTAGA-PEG2-RM26 (4.8 ± 0.5 nM). The kinetic binding studies showed KD values in the picomolar range that followed the same pattern as the IC50 data. The biodistribution of all compounds was studied in BALB/c nu/nu mice bearing PC-3 prostate cancer xenografts. Tumor targeting and biodistribution studies displayed rapid clearance of radioactivity from the blood and normal organs via kidney excretion. All conjugates showed similar uptake in tumors at 4 h p.i. The radioactivity accumulation in GRPR-expressing organs was significantly lower for DOTA- and DOTAGA-containing constructs compared to those containing NOTA and NODAGA. 111In-NOTA-PEG2-RM26 with a positively charged complex showed the highest initial uptake and the slowest clearance of radioactivity from the liver. At 4 h p.i., DOTA- and DOTAGA-coupled analogs showed significantly higher tumor-to-organ ratios compared to NOTA- and NODAGA-containing variants. The NODAGA conjugate demonstrated the

  1. Increasing the Net Negative Charge by Replacement of DOTA Chelator with DOTAGA Improves the Biodistribution of Radiolabeled Second-Generation Synthetic Affibody Molecules.

    PubMed

    Westerlund, Kristina; Honarvar, Hadis; Norrström, Emily; Strand, Joanna; Mitran, Bogdan; Orlova, Anna; Eriksson Karlström, Amelie; Tolmachev, Vladimir

    2016-05-01

    A promising strategy to enable patient stratification for targeted therapies is to monitor the target expression in a tumor by radionuclide molecular imaging. Affibody molecules (7 kDa) are nonimmunoglobulin scaffold proteins with a 25-fold smaller size than intact antibodies. They have shown an apparent potential as molecular imaging probes both in preclinical and clinical studies. Earlier, we found that hepatic uptake can be reduced by the incorporation of negatively charged purification tags at the N-terminus of Affibody molecules. We hypothesized that liver uptake might similarly be reduced by positioning the chelator at the N-terminus, where the chelator-radionuclide complex will provide negative charges. To test this hypothesis, a second generation synthetic anti-HER2 ZHER2:2891 Affibody molecule was synthesized and labeled with (111)In and (68)Ga using DOTAGA and DOTA chelators. The chelators were manually coupled to the N-terminus of ZHER2:2891 forming an amide bond. Labeling DOTAGA-ZHER2:2891 and DOTA-ZHER2:2891 with (68)Ga and (111)In resulted in stable radioconjugates. The tumor-targeting and biodistribution properties of the (111)In- and (68)Ga-labeled conjugates were compared in SKOV-3 tumor-bearing nude mice at 2 h postinjection. The HER2-specific binding of the radioconjugates was verified both in vitro and in vivo. Using the DOTAGA chelator gave significantly lower radioactivity in liver and blood for both radionuclides. The (111)In-labeled conjugates showed more rapid blood clearance than the (68)Ga-labeled conjugates. The most pronounced influence of the chelators was found when they were labeled with (68)Ga. The DOTAGA chelator gave significantly higher tumor-to-blood (61 ± 6 vs 23 ± 5, p < 0.05) and tumor-to-liver (10.4 ± 0.6 vs 4.5 ± 0.5, p < 0.05) ratios than the DOTA chelator. This study demonstrated that chelators may be used to alter the uptake of Affibody molecules, and most likely other scaffold-based imaging probes, for improvement

  2. Measurement of Quadrupole Interactions in LaMO3 (M = Cr, Fe, Co) Perovskites by TDPAC

    NASA Astrophysics Data System (ADS)

    Junqueira, A. C.; Dogra, R.; Carbonari, A. W.; Saxena, R. N.; Mestnik-Filho, J.; Moralles, M.

    2001-11-01

    The perturbed angular correlation (PAC) technique has been used to study the electric field gradient (EFG) in LaCoO3 perovskite. The results are compared with those for LaCrO3, LaFeO3 measured earlier. The PAC probe, 111In → 111Cd, was introduced in the oxide lattice by means of chemical reaction during sample preparation. In the present work, the temperature dependence of the electric quadrupole interaction parameters, for LaCoO3 was investigated. The resulting systematics of EFG at 111Cd, in La(Cr,Fe,Co)O3 perovskites, reveals a linear dependence with temperature.

  3. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    PubMed

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer. PMID:9676842

  4. Capillary electrophoresis for regulatory analysis: is it ready? Problems encountered during an interlaboratory study utilizing capillary electrophoresis.

    PubMed

    Mopper, B; Sciacchitano, C J

    1997-01-01

    Recently, the Northeast Regional Laboratory of the Food and Drug Administration conducted a collaborative study on the method to determine histamine in tuna by capillary electrophoresis. This study, under the guidance of the AOAC International, was the first of its kind involving the use of CE and was undertaken to establish official monograph status. The results of the collaborative study, however, were highly variable. Percent recovery data obtained by 11 collaborators ranged from 54 to 281%, with an average of 111%. In this paper, problems with reproducibility, and factors such as low sensitivity, noisy baselines, and variable migration times encountered by collaborators using various commercial capillary electrophoresis units are discussed. PMID:9624572

  5. A high performance hybrid battery based on aluminum anode and LiFePO4 cathode

    SciTech Connect

    Sun, Xiao-Guang; Bi, Zhonghe; Liu, Hansan; Bridges, Craig A.; Paranthaman, Mariappan Parans; Dai, Sheng; Brown, Gilbert M.

    2015-12-07

    A unique battery hybrid utilizes an aluminum anode, a LiFePO4 cathode and an acidic ionic liquid electrolyte based on 1-ethyl-3-methylimidazolium chloride (EMImCl) and aluminum trichloride (AlCl 3) (EMImCl-AlCl 3, 1-1.1 in molar ratio) with or without LiAlCl4 is proposed. This hybrid ion battery delivers an initial high capacity of 160 mAh g-1 at a current rate of C/5. It also shows good rate capability and cycling performance.

  6. Probing the ultrafast electron transfer at the CuPc/Au(111) interface

    SciTech Connect

    Chen Wei; Wang Li; Qi Dongchen; Chen Shi; Gao Xingyu; Wee, Andrew Thye Shen

    2006-05-01

    Core-hole clock spectroscopy and near-edge x-ray-absorption fine structure measurements have been used to investigate the ultrafast electron transfer dynamics at the Copper(II) phthalocyanine (CuPc)/Au(111) interface. It was found that the strong electronic coupling between the first layer of CuPc molecules and Au(111) substrate favors ultrafast electron transfer from the lowest unoccupied molecular orbital of the CuPc molecules to the conduction band of Au(111) in the time scale of {approx}6 fs. In contrast, the intermolecular electron transfer within multilayers of CuPc molecules via the weak van der Waals interaction was much slower.

  7. PAC studies on impurities in ZnO

    NASA Astrophysics Data System (ADS)

    Deubler, S.; Meier, J.; Schütz, R.; Witthuhn, W.

    1992-01-01

    Acceptor-donor pairs in ZnO are studied by the perturbed angular correlation spectroscopy (PAC) using radioactive 111In/ 111Cd probe atoms. In undoped ZnO the trapping of O-vacancies as well as the trapping of Zn-interstitials at the probe atoms which are located at substitutional Zn sites is observed after different sample treatments. In Cu-, Li-, and Na-doped ZnO the acceptor impurities form complexes with the In donors. The structure of these complexes is given and compared with theoretical calculations.

  8. Coalescence of 3-phenyl-propynenitrile on Cu(111) into interlocking pinwheel chains.

    PubMed

    Luo, Miaomiao; Lu, Wenhao; Kim, Daeho; Chu, Eric; Wyrick, Jon; Holzke, Connor; Salib, Daniel; Cohen, Kamelia D; Cheng, Zhihai; Sun, Dezheng; Zhu, Yeming; Einstein, T L; Bartels, Ludwig

    2011-10-01

    3-phenyl-propynenitrile (PPN) adsorbs on Cu(111) in a hexagonal network of molecular trimers formed through intermolecular interaction of the cyano group of one molecule with the aromatic ring of its neighbor. Heptamers of trimers coalesce into interlocking pinwheel-shaped structures that, by percolating across islands of the original trimer coverage, create the appearance of gear chains. Density functional theory aids in identifying substrate stress associated with the chemisorption of PPN's acetylene group as the cause of this transition. PMID:21992333

  9. Effect of heavy noble gas ion irradiation on terahertz emission efficiency of InP (100) and (111) crystal planes

    NASA Astrophysics Data System (ADS)

    Radhanpura, K.; Lewis, R. A.; Sirbu, L.; Enachi, M.; Tiginyanu, I. M.; Skuratov, V. A.

    2014-09-01

    Emission of terahertz (THz) electromagnetic radiation from heavily-doped (5 × 1018 cm-3) (100) and (111) InP bulk materials and nanoporous honeycomb membranes, irradiated with heavy noble gas (Kr and Xe) ions, is presented. Irradiating samples with Kr or Xe improves THz emission efficiency. For (111) samples, as for unirradiated samples, the irradiated porous structures generate more THz radiation than their bulk counterparts. On the other hand, in contrast to unirradiated (100) samples, the irradiated (100) samples show a decrease in THz emission with porosity. We attribute this behaviour to changes in the local electric field due to the combined effect of the irradiation and nanoporosity.

  10. Wall-loss distribution of charge breeding ions in an electron cyclotron resonance ion source

    SciTech Connect

    Jeong, S. C.; Oyaizu, M.; Imai, N.; Hirayama, Y.; Ishiyama, H.; Miyatake, H.; Niki, K.; Okada, M.; Watanabe, Y. X.; Otokawa, Y.; Osa, A.; Ichikawa, S.

    2012-02-15

    We investigated the ion-loss distribution on the sidewall of an electron cyclotron resonance (ECR) plasma chamber using the 18-GHz ECR charge breeder at the Tokai Radioactive Ion Accelerator Complex (TRIAC). Similarities and differences between the ion-loss distributions (longitudinal and azimuthal) of different ion species (i.e., radioactive {sup 111}In{sup 1+} and {sup 140}Xe{sup 1+} ions that are typical volatile and nonvolatile elements) was qualitatively discussed to understand the element dependence of the charge breeding efficiency. Especially, the similarities represent universal ion loss characteristics in an ECR charge breeder, which are different from the loss patterns of electrons on the ECRIS wall.

  11. A high performance hybrid battery based on aluminum anode and LiFePO4 cathode.

    PubMed

    Sun, Xiao-Guang; Bi, Zhonghe; Liu, Hansan; Fang, Youxing; Bridges, Craig A; Paranthaman, M Parans; Dai, Sheng; Brown, Gilbert M

    2016-01-28

    A novel hybrid battery utilizing an aluminum anode, a LiFePO4 cathode and an acidic ionic liquid electrolyte based on 1-ethyl-3-methylimidazolium chloride (EMImCl) and aluminum trichloride (AlCl3) (EMImCl-AlCl3, 1-1.1 in molar ratio) with or without LiAlCl4 is proposed. The hybrid ion battery delivers an initial high capacity of 160 mA h g(-1) at a current rate of C/5. It also shows good rate capability and cycling performance. PMID:26666453

  12. The Kyoto Protocol: A business perspective

    SciTech Connect

    Malin, C.B.

    1998-01-19

    Governments have made a tentative start in responding to climate change. In marathon negotiating sessions that extended into an extra day Dec. 1--11 in Kyoto, Japan, representatives from more than 160 governments hammered out the Kyoto Protocol to the United Nations Framework Convention on Climate Change (FCCC). The protocol calls for developed countries to reduce emissions of greenhouse gases (GHGs) on averaged by 5.2% below 1990 levels by the years 2008--2012. Developing countries have no new obligations. The paper discusses the agreement, ratification, future questions, business role, and the challenge.

  13. Radiochemical separation methods for preparation of biomedical cyclotron radionuclides

    NASA Astrophysics Data System (ADS)

    Zaitseva, N. G.; Dmitriev, S. N.

    1999-01-01

    A short review of the radiochemical methods for preparation of widely used or promising cyclotronproduced radionuclides for nuclear medicine and biomedical or environmental studies is given. The presented data include the current status of the production of some gamma-emitters (97Ru, 111In, 123I, 201Tl), generator-pairs (68Ge/68Ga, 82Sr/82Rb, 128Ba/128Cs, 178W/178Ta), radioisotopes for metabolism studies (26Al, 67Cu, 237Pu) and actinides tracers for environmental researches (235Np, 236Np, 236Pu). The conditions for preparation of high-purity isotopes have been investigated and procedures including target chemistry design were developed.

  14. Effect of long-time, elevated-temperature exposures to vacuum and lithium on the properties of a tantalum alloy, T-111

    NASA Technical Reports Server (NTRS)

    Buzzard, R. J.; Sheffler, K. D.

    1974-01-01

    The effect of long-term, elevated-temperature vacuum and lithium exposures on the mechanical properties of T-111 (Ta-8W-2Hf) is determined. Exposure conditions were for 1000 hours at 980 or 1315 C, 5000 hours at 1315 C, and a duplex temperature exposure of 1000 hours at 980 C plus 4000 hours at 1040 C. The exposures resulted in reduced tensile and creep strengths of the T-111 in the 900 to 1100 C temperature range where a dynamic strain-age-strengthening mechanism is operative in this alloy. This strength reduction was attributed to the depletion of oxygen from solid solution in this alloy.

  15. Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets

    PubMed Central

    Osim, E. E.; Wyllie, J. H.

    1983-01-01

    1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111In oxine to tag individual platelets and with 14C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111In and 14C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14C behaved like the 111In. However, in control rabbits the half-life for 14C was 38·0 hr which is significantly longer than for 111In (P < 0·005). 14C also disappeared more slowly than the 111In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14C

  16. Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models.

    PubMed

    Pujatti, Priscilla B; Foster, Julie M; Finucane, Ciara; Hudson, Chantelle D; Burnet, Jerome C; Pasqualoto, Kerly F M; Mengatti, Jair; Mather, Stephen J; de Araújo, Elaine B; Sosabowski, Jane K

    2015-02-01

    We evaluated and compared a new bombesin analog [Tyr-Gly5, Nle(14)]-BBN(6-14) conjugated to DOTA or DTPA and radiolabeled with In-111 in low and high GRPR expressing tumor models. Both peptides were radiolabeled with high radiochemical purity and specific activity. In vitro assays on T-47D, LNCaP and PC-3 cells showed that the affinity of peptides is similar and a higher binding and internalization of DOTA-peptide to PC-3 cells was observed. Both peptides could target PC-3 and LNCaP tumors in vivo and both tumor types could be visualized by microSPECT/CT. PMID:25479439

  17. Gallium-67 complexes as radioactive markers to assess gastric and colonic transit

    SciTech Connect

    Bellen, J.C.; Chatterton, B.E.; Penglis, S.; Tsopelas, C.

    1995-03-01

    Constipation and gastroparesis are gastrointestinal tract disorders that can be assessed by using radioactive markers in conjunction with scintigraphic techniques. Indium-111-DTPA is the radiopharmaceutical of choice for treating colonic transit in constipated patients, but it is an expensive product and its availability has been unreliable. Indium-113m-DTPA was the tracer used in our study to determine the liquid gastric emptying rate in dual-isotope solid-liquid emptying studies, however, cessation of the {sup 113}Sn/{sup 113m}In generator production makes it unavailable. Thus, development of alternative tracers to {sup 111}In-DTPA and {sup 113m}In-DTPA was essential. Gallium-67-citrate and {sup 67}Ga-EDTA were compared to {sup 111}In-DTPA to assess their efficacy for exclusive retention in the GI tract. These markers were orally administered into rats and their three-day cumulative fecal excretion, urine excretion and carcass retention were measured. An in vitro gastric emptying model was used to determine liquid phase partitioning of {sup 113m}In-DTPA, {sup 67}Ga-citrate and {sup 67}Ga-EDTA at 37{degrees}. Gallium-67-citrate was predominantly excreted in the feces (97.2% {+-} 0.2%) after three days, with negligible urine excretion (0.1% {+-} 0.0%) and carcass retention (0.6% {+-} 0.2%). These results are analogous to those obtained for {sup 111}In-DTPA for fecal excretion (96.7% {+-} 2.6%), urine excretion (0.6% {+-} 0.0%) and retention in the carcass (0.2% {+-} 0.0%). Gallium-67-EDTA showed similar partitioning in the liquid phase of the gastric emptying model compared with {sup 113m}In-DTPA. Gallium-67-citrate is an economical and readily available alternative to {sup 111}In-DTPA as a colonic transit radiopharmaceutical. Gallium-67-EDTA is also an alternative to {sup 113m}In-DTPA for assessing liquid-phase emptying in a dual-isotope solid/liquid gastric emptying study. 17 refs., 3 figs., 2 tabs.

  18. Methods of assessment of thrombosis in vivo

    SciTech Connect

    Dewanjee, M.K.

    1987-01-01

    The contributions of platelets and clotting factors in thrombosis on injured vessel and cardiovascular prostheses have been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and humans with /sup 111/In-labeled platelets, /sup 123/I- and /sup 131/I-labeled fibrinogen, /sup 111/In-labeled antibody to the fibrinogen receptor on the platelet membrane and to fibrin. Thrombus localization by imaging was possible for large thrombus in vessel with deep injury of thrombogenic surface in the acute phase. A single layer of adherent platelets could not be imaged, due to the high background radioactivity present in blood. Thrombogenicity of grafts was compared with that of contralateral vessel. The dynamic process of platelet deposition could be followed accurately using the in vivo imaging technique. In addition, in vitro quantification permits determination of platelet and fibrin density and of the number of fibrin monomers per platelet in thrombus. The roles of prostacyclin, thromboxane inhibitors, and nonsteroidal antiinflammatory drugs have also been evaluated in animals models and humans. The tracer techniques thus provide invaluable information about platelet-fibrin deposition, its organization and dissolution, and for development of less thrombogenic surfaces for use in cardiovascular prostheses. 53 references.

  19. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans

    SciTech Connect

    Bjarnason, I.; Zanelli, G.; Smith, T.; Prouse, P.; Williams, P.; Smethurst, P.; Delacey, G.; Gumpel, M.J.; Levi, A.J.

    1987-09-01

    This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an /sup 111/In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal /sup 111/In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (/sup 75/Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.

  20. Skin contamination by radiopharmaceuticals and decontamination strategies.

    PubMed

    Bolzinger, M A; Bolot, C; Galy, G; Chabanel, A; Pelletier, J; Briançon, S

    2010-12-15

    The aim of the present study was to evaluate the percutaneous penetration of five common radiopharmaceuticals ((99m)Tc, (67)Ga, (125)I, (111)In and (51)Cr) and to evaluate the effect of decontamination by a detergent solution dedicated to hospital institutions for that purpose. The skin kinetic profiles were established by using the in vitro Franz cell method over 24h. The skin distribution in each skin layer was quantified after 6h exposure time and the efficacy of the detergent solution to remove radionuclides was evaluated also after 6h. The most striking result was the repartition into two classes of kinetic profiles: (125)I and (99m)Tc permeated quickly (∼60% of applied activity after 24h) while the 3 other radionuclides permeated slowly (from ∼2.75% for (67)Ga to ∼10% of applied activity for (111)In). The lag times, i.e. the time necessary to cross the skin varied from 20min for (99m)Tc to 5h for (51)Cr, which accumulated in skin compartments. Skin washings with the detergent solution were particularly efficient for this radionuclide, contrary to the others for which the washing procedure should be applied earlier. The permeation of ions was dependent on their chemical and physical forms and on their salting-in or salting-out effects (coordination state and Hofmeister series). PMID:20888404

  1. Quantitation of platelet and fibrinogen-fibrin deposition on components of tissue valves (Ionescu-Shiley) in calves

    SciTech Connect

    Dewanjee, M.K.; Solis, E.; Lenker, J.; Tidwell, C.; Mackey, S.; Didisheim, P.; Kaye, M.P.

    1986-07-01

    With /sup 111/In-labeled platelets and /sup 125/I-labeled bovine fibrinogen, regional mapping of platelet and fibrinogen deposition on leaflets and sewing rings was obtained. Ten Holstein calves received 25-mm mitral valves (ISLM) and were killed 1, 14, and 30 days after implantation. Twenty-four hours before the calves were killed, 350 to 450 microCi of /sup 111/In-labeled platelets and 200 to 250 microCi of /sup 125/I-labeled bovine fibrinogen were administered intravenously. The components of the tissue valves, i.e., three leaflets and sewing rings, were separated. Each leaflet was cut into four sections: free edge, central zone, flexion zone, and attachment zone. From the radioactivity in blood, leaflet zones, sewing rings, area of leaflet zones, platelet count, and fibrinogen level in blood, the mean regional density of adherent platelets, fibrinogen-fibrin, and fibrinogen/platelet were calculated. The density of platelets and fibrinogen deposited on the components of the valves decreases with time postimplantation. The number of fibrinogen molecules per platelet is fivefold to 20-fold higher than that of the receptor concentration on platelets on leaflet zones, suggesting the heterogeneity of fibrinogen-fibrin in thrombus and components of the valve.

  2. Noninvasive radioisotopic technique for detection of platelet deposition on bovine pericardial mitral-valve prosthesis and in vitro quantification of visceral microembolism in dogs

    SciTech Connect

    Dewanjee, M.K.; Trastek, V.F.; Tago, M.; Torianni, M.; Kaye, M.P.

    1983-01-01

    Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in dogs was observed noninvasively by use of /sup 111/In-labeled platelets and quantified after sacrifice at one, 14 and 30 days postimplantation (300-400 microCi of labeled platelets having been injected 24 hrs previously). Thrombosis on the sewing ring and pericardial leaflets at one and 14 days and on the leaflets at 30 days was delineated in scintiphotos. In vitro quantification (% injected dose) indicated that the sewing ring and perivalvular tissue retained 0.75% of labeled platelets at one day postimplantation, 0.084% at 14 days, and 0.0042% at 30 days. Platelet survival was reduced to 38 hrs at 21 days postimplantation but returned toward the normal (50 hrs) with endothelial covering of the sewing ring. Microemboli in lung and kidney, as measured by tissue/blood radioactivity ratio, decreased significantly at 30 days. /sup 111/In-labeled platelets thus provide a sensitive marker for noninvasive imaging and in vitro quantification of platelet deposition on valvular prostheses and microemboli trapped in viscera.

  3. The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

    SciTech Connect

    Castle, V.P.; Shulkin, B.L.; Coates, G.; Andrew, M. )

    1989-11-01

    We have utilized {sup 111}In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, {sup 111}In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma.

  4. Radioisotopic model for investigating thromboembolism in the rabbit

    SciTech Connect

    May, G.R.; Herd, C.M.; Butler, K.D.; Page, C.P. )

    1990-08-01

    111Indium ({sup 111}In)-oxine labeled platelets have been used in a variety of species to assess platelet behavior in vivo. We have shown that {sup 111}In-oxine is a suitable label for rabbit platelets and, using a noninvasive technique for the automated, continuous, external imaging of these radiolabeled platelets, we have shown that intravenous adenosine disphosphate (ADP), collagen, platelet activating factor (PAF), and thrombin all elicit dose-related accumulation of platelet-(but not erythrocyte-)associated radioactivity in the thoracic region and a concomitant fall in both the cranial and hindlimb regions of the anesthetized rabbit. Intracarotid (i.c.) ADP, collagen, PAF, and thrombin also produce dose-related increases in platelet-associated radioactivity in the thoracic and decreases in the cranial and hindlimb regions. However, the initial fall in cranial counts induced by i.c. thrombin was followed by a marked increase that was sustained for up to 3 hr. These results suggest this may be a useful model for investigating the mechanisms of platelet activation in the arterial and venous circulations in vivo and may provide a novel model for investigating thromboembolic events in the cerebral circulation.

  5. Space Shuttle Main Engine Liquid Air Insulation Redesign Lessons Learned

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell; Carroll, Paul; Head, Kenneth; Fasheh, John; Stuart, Jessica

    2010-01-01

    The Space Shuttle Main Engine Liquid Air Insulation redesign was required to prevent the reoccurance of the STS-111 High Pressure Speed Sensor In-Flight Anomaly. The STS-111 In-Flight Anomaly Failure Investigation Team's initial redesign of the High Pressure Fuel Turbopump Pump End Ball Bearing Liquid Air Insulation failed the certification test by producing Liquid Air. The certification test failure indicated not only the High Pressure Fuel Turbopump Liquid Air Insulation, but all other Space Shuttle Main Engine Liquid Air Insulation. This paper will document the original Space Shuttle Main Engine Liquid Air STS-111 In-Flight Anomaly investigation, the heritage Space Shuttle Main Engine Insulation certification testing faults, the techniques and instrumentation used to accurately test the Liquid Air Insulation systems on the Stennis Space Center SSME test stand, the analysis techniques used to identify the Liquid Air Insulation problem areas and the analytical verification of the redesign before entering certification testing, Trade study down selected to three potential design solutions, the results of the development testing which down selected the final Liquid Air Redesign are also documented within this paper.

  6. Enhancement of monoclonal antibody binding to melanoma with single dose radiation or hyperthermia

    SciTech Connect

    Stickney, D.R.; Gridley, D.S.; Kirk, G.A.; Slater, J.M.

    1987-01-01

    We undertook this study to determine whether radiation (10 Gray, single dose) or water bath hyperthermia (41 degrees C, 45 min) could enhance binding of /sup 111/In-labeled anti-p97a monoclonal antibody (MAb) to human melanoma tumors transplanted subcutaneously into nude mice. Sixty animals were given injections of 1-2 X 10(7) Brown C5513 melanoma cells. At 1-2 weeks postinjection, two-thirds of the mice were treated (one-third served as controls). Within 3 hours after treatment, each animal was given iv 2 muCi /sup 111/In-anti-p97a MAb. At 24 and 48 hours thereafter, whole-body scans were done with the use of a MaxiCamera 300 A/M unit, and the ratio of activity at the tumor and liver was determined. Some animals were kept for 7 days posttreatment, whereas others were taken after the 48-hour scan for determination of biodistribution of the radiolabeled complex. Enhancement of MAb binding was demonstrated by either modality, although enhancement was more consistent with radiation. The therapeutic efficacy of MAb may be enhanced with increased binding of radioactive MAb complexes through single dose radiation or hyperthermia.

  7. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    SciTech Connect

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. )

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  8. Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate.

    PubMed

    Betebenner, D A; Carney, P L; Zimmer, A M; Kazikiewicz, J M; Brücher, E; Sherry, A D; Johnson, D K

    1991-01-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance. PMID:1907855

  9. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R.; Evenson, W.E.; Rasera, R.L.; Sommers, J.A.

    1991-12-31

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  10. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R. . Dept. of Physics); Evenson, W.E. . Dept. of Physics and Astronomy); Rasera, R.L. . Dept. of Physics); Sommers, J.A. )

    1991-01-01

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  11. The role of octreoscan in thyroid eye disease.

    PubMed

    Krassas, G E; Kahaly, G J

    1999-05-01

    Until recently there was no imaging technique available which could demonstrate pathological changes in orbital tissues and could be regarded as a reliable measure of inflammation in thyroid eye disease (TED). Pentetreotide (a synthetic derivative of somatostatin) labelled with 111In has been used to localize tumours which possess surface or membrane receptors for somatostatin in vivo using a gamma camera (1). This technique visualizes somatostatin receptors in endocrine-related tumours in vivo and predicts the inhibitory effect of the somatostatin analogue octreotide on hormone secretion by the tumours (1). By applying 111In-DTPA-d-Phe octreotide scintigraphy (octreoscan), accumulation of the radionuclide was also detected in both the thyroid and orbit of patients with Graves' disease (2-4). If peak activity in the orbit 5h after injection of radiolabelled octreotide is set at 100%, a decrease to 40+/-4% is found at 24h, significantly different from the decrease in blood pool radioactivity, which is 15+/-4% at 24h. Accumulation of the radionuclide is most probably due to the presence in the orbital tissue of activated lymphocytes bearing somatostatin receptors (5). Alternative explanations are binding to receptors on other cell types (e.g. myoblasts, fibroblasts or endothelial cells) or local blood pooling due to venous stasis by the autoimmune orbital inflammation. PMID:10229898

  12. Myocardial distribution of indium-111-antimyosin Fab in acute inferior and right ventricular infarction: comparison with technetium-99m-pyrophosphate imaging and histologic examination

    SciTech Connect

    Nakata, T.; Sakakibara, T.; Noto, T.; Shoji, T.; Tsuda, T.; Kubota, M.; Hattori, A.; Iimura, O. )

    1991-05-01

    In a postmortem study of a 69-yr-old female patient who had suffered 2 yr previously a non-Q-wave anterior infarction and who had sustained just seven days earlier a left inferior and right ventricular infarction, the distribution of {sup 111}In-antimyosin Fab was compared to the results of {sup 99}mTc-pyrophosphate imaging and histologic examination. Indium-111-antimyosin Fab imaging could not be performed because of cardiogenic shock. However, postmortem gamma scintillation counting revealed increased activities of antimyosin Fab in the inferoapical and right ventricular infarcted regions in which {sup 99}mTc-pyrophosphate positive imagings were observed; in contrast, a histologically confirmed old subendocardial anterior infarction had no definite activity. Thus, the myocardial distribution of {sup 111}In-antimyosin Fab corresponded well to the results of {sup 99}mTc scintigrams and histologic examinations in a human heart, suggesting that this technique could be useful in vivo for detecting several-day-old myocardial infarction of the right ventricle as well as the left ventricle. Tissue from the 2-yr-old infarction was not identified by this technique.

  13. Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy

    NASA Astrophysics Data System (ADS)

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-01

    We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

  14. Electric field gradient in nanostructured SnO2 studied by means of PAC spectroscopy using 111Cd or 181Ta as probe nuclei

    NASA Astrophysics Data System (ADS)

    Ramos, Juliana Marques; Martucci, Thiago; Carbonari, Artur Wilson; de Souza Costa, Messias; Saxena, Rajendra Narain; Vianden, Reiner

    2013-05-01

    Electric quadrupole interactions were studied in pure and Mn-doped powder samples and thin films of SnO2 using perturbed γγ angular correlation spectroscopy (PAC). The powder samples were prepared by Sol gel method and the thin film were prepared on the Si (100) substrate by sputtering technique using Sn in the oxygen atmosphere. The samples were characterized by x-ray diffraction, energy dispersive spectroscopy and scanning electron microscopy. The thickness of the film was 100 nm. The average particle size of the SnO2 powder samples was determined to be smaller than 60 nm. The radioactive 111In and 181Hf tracers were introduced in the powder samples during the sol gel chemical process. Radioactive 111In was implanted on the SnO2 thin films using the University of Bonn ion implanter (BONIS). PAC measurements were carried out in a four BaF2 detector spectrometer in the temperature range of 77-973 K for samples annealed at different temperatures. The PAC results for both nuclear probes show the presence of two electric quadrupole interactions. The major fractions in both cases correspond to the substitutional sites in the rutile phase of SnO2. The results are compared with previous PAC measurements.

  15. Nuclear Imaging of Amyloidosis

    PubMed Central

    Cytawa, Wojciech; Teodorczyk, Jacek; Lass, Piotr

    2014-01-01

    Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. 123I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. 99mTc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as 201Tl, 123I-mIBG, together with 111In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. 67Ga-citrate and 99mTc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with 131I or 111In. Among PET tracers, 11C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge. PMID:25071873

  16. Hepatobiliary handling of iodine-125-Tyr3-octreotide and indium-111-DTPA-D-Phe1-octreotide by isolated perfused rat liver.

    PubMed

    de Jong, M; Bakker, W H; Breeman, W A; van der Pluijm, M E; Kooij, P P; Visser, T J; Docter, R; Krenning, E P

    1993-11-01

    Radiolabeled bioactive peptides may show receptor-mediated binding to tumors, making them suitable for scintigraphic imaging. The liver is an important organ for peptide clearance. To gain insight into the uptake and intracellular processing of somatostatin analogs, we compared the hepatobiliary handling of 125I-Tyr3-octreotide and 111In-DTPA-D-Phe1-octreotide, which are successfully used to image somatostatin receptor-positive tumors in vivo in isolated recirculating perfused rat livers. Sixty minutes following administration of the radiolabeled peptides, perfusion medium and biliary radioactivity were analyzed. Radioiodinated Tyr3-octreotide was rapidly cleared by the liver and 60% of the dose was excreted intact into the bile after 60 min. In contrast, 111In-DTPA-D-Phe1-octreotide was not cleared by the liver; medium radioactivity levels remained about constant and only 2% of the dose was found in the bile. These results are in agreement with in vivo findings in rats and humans. We concluded that isolated rat liver perfusion is a good system to rapidly gain insight into the hepatic handling of radiopharmaceuticals. PMID:8229254

  17. Stability of erythrocyte ghosts: a gamma-ray perturbed angular correlation study.

    PubMed Central

    Kruse, C A; Tin, G W; Baldeschwieler, J D

    1983-01-01

    The structural integrity of erythrocyte ghosts made by the preswell and slow-dialysis techniques has been studied in vitro by use of gamma-ray perturbed angular correlation (PAC) techniques and also by standard in vitro leakage methods employing sequestered labeled markers. Complexes of 111In3+ and nitrilotriacetate were encapsulated in ghosts made from human, rabbit, rat, and mouse erythrocytes, and their leakage was monitored by both methods. In addition, 125I-labeled bovine serum albumin was encapsulated, and ghost integrity was monitored by conventional leakage measurements. With the PAC technique the percentage of material released from human ghosts was determined quantitatively, and the results were equivalent to those obtained by the conventional method. In addition, at various times after intravenous injection, tissue distribution of the ghosts in the mouse was studied. The percent injected dose per gram of tissue of the labeled surface proteins of erythrocyte ghosts in circulation approximated that of the entrapped labeled albumin. This suggests that the ghost membrane and contents are strongly associated in vivo. Large 125I-labeled bovine serum albumin molecules and small 111In3+-nitrilotriacetate complexes were delivered in high quantitites to the lung initially, and to the liver and spleen. Because erythrocyte ghosts have the ability to entrap a wide range of substances and deliver them to specific organs, ghosts may be preferable to other drug carriers or drug therapy for treatment of certain disorders. PMID:6572379

  18. Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.

    PubMed Central

    Wangberg, B.; Forssell-Aronsson, E.; Tisell, L. E.; Nilsson, O.; Fjalling, M.; Ahlman, H.

    1996-01-01

    After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors. Images Figure 1 Figure 2 Figure 3 PMID:8611378

  19. 111-Indium labelled autologous leucocytes in diagnosis of inflammatory bowel disease

    SciTech Connect

    Wandall, J.H.; Edeling, C.J.; Jensen, J.T.; Lund, J.O.; Bonnevie, O.; Haxholdt, H.; Jensen, H.C.; Matzen, P.; Myschetsky, P.S.; Nielsen, A.M.

    1984-01-01

    111-Indium labelled leucocytes have been used to visualize inflammatory lesions in ulcerative colitis (CU) and in Crohn's disease (CD). The aim of this study was to compare findings by scintigraphy, radiology and endoscopy. Material: Twelve patients with CU and 15 patients with CD were studied. All patients were non-febrile. Two patients received prednisolone 5 mg/daily, 8 sulphasalazine. Methods: Autologous leucocytes were labelled with 111-In-Oxine and given i.v. Scintigrams were obtained 3 and 24 hrs. p.i. Double contrast x-ray studies were done of the colon and small intestine after 2 and 14 days respectively. Colonscopy with biopsy was done after 4 days. Results: Active lesions were found in 24 and 27 patients. Scintigrams 24 hrs.p.i. did not give and additional information compared with scintigrams 3 hrs.p.i. Intraluminal activity masked the location and extension of lesions after 24 hrs. Excretion in the stool was 2.4-25.8% of administered activity. Compared with scintigraphy a corresponding extension and location was found by colonscopy. In 4 patients x-ray of the colon was normal but scintigraphy and colonscopy showed active inflammation. Conclusion: Scintigraphy after injection of 111-In labelled leucocytes is a atraumatic method for visualization of inflammatory lesions in UC and CD. Furthermore, it appears to be more sensitive than conventional x-ray studies.

  20. The white blood cell scan in orthopedics

    SciTech Connect

    Propst-Proctor, S.L.; Dillingham, M.F.; McDougall, I.R.; Goodwin, D.

    1982-08-01

    A new nuclear scanning technique was found more specific for bone, joint, and soft tissue infections than any previously described scanning technique. The leukocyte scan, whereby a patient's own cells are labeled with a radioactive tagging agent (/sup 111/In oxine), can distinguish an active infectious process from other pain-inducing conditions. Ninety-seven /sup 111/In labeled autologous leukocyte scans were performed in 88 patients. The findings in 17 of 40 patients scanned for possible acute osteomyelitis, six of nine for suspected septic arthritis, and six for possible soft tissue infections, were positive. Subsequent clinical courses verified the infectious nature of these processes in all patients. Patients who had chronic osteomyelitis (14), bony metastases (four patients), heterotopic ossification (three), and degenerative arthritis (two) demonstrated negative findings. Of the seven patients scanned for acute long-bone fractures, one demonstrated positive findings. Nine scans demonstrated positive findings without determined causes. The leukocyte scan is a useful addition to the diagnostic tools of the orthopedic surgeon.

  1. Acute osteomyelitis: advantage of white cell scans in early detection

    SciTech Connect

    Raptopoulos, V.; Doherty, P.W.; Goss, T.P.; King, M.A.; Johnson, K.; Gantz, N.M.

    1982-12-01

    Acute osteomyelitis was induced in 18 rabbits after direct injection of a solution of Staphylococcus aureus culture into a proximal tibial metaphysis. Serial plain radiographs and radionuclide studies with /sup 111/In oxide labeled while blood cells and /sup 99m/Tc methylene diphosphonate were performed over the next 4 weeks. Visual and quantitative analysis by measuring the isotope activity of /sup 111/In and /sup 99m/Tc over the infected tibias as compared with the opposite bones revealed that the white blood cell scans were positive in 15 (83%) of the 18 rabbits during the first week after injection of the microorganism. During the same period, the /sup 99m/Tc bone scans were positive in only 22% of the animals (p less than 0.005). In the animals that survived, both white blood cell and bone scans were positive during the second week, and thereafter, the bone scans revealed consistently higher activity than was observed with white blood cell scans. Computed tomography performed in six rabbits revealed an increased attenuation coefficient of the medullary cavities in the infected bones of four animals during the first week and of one more during the second week. Plain radiographs became positive after the 12th day. Results indicate that in patients with suspected acute osteomyelitis, white blood cell scans and probably computed tomography can detect the disease earlier than /sup 99m/Tc bone scans and plain radiographs.

  2. Validation of the Monte Carlo simulator GATE for indium-111 imaging.

    PubMed

    Assié, K; Gardin, I; Véra, P; Buvat, I

    2005-07-01

    Monte Carlo simulations are useful for optimizing and assessing single photon emission computed tomography (SPECT) protocols, especially when aiming at measuring quantitative parameters from SPECT images. Before Monte Carlo simulated data can be trusted, the simulation model must be validated. The purpose of this work was to validate the use of GATE, a new Monte Carlo simulation platform based on GEANT4, for modelling indium-111 SPECT data, the quantification of which is of foremost importance for dosimetric studies. To that end, acquisitions of (111)In line sources in air and in water and of a cylindrical phantom were performed, together with the corresponding simulations. The simulation model included Monte Carlo modelling of the camera collimator and of a back-compartment accounting for photomultiplier tubes and associated electronics. Energy spectra, spatial resolution, sensitivity values, images and count profiles obtained for experimental and simulated data were compared. An excellent agreement was found between experimental and simulated energy spectra. For source-to-collimator distances varying from 0 to 20 cm, simulated and experimental spatial resolution differed by less than 2% in air, while the simulated sensitivity values were within 4% of the experimental values. The simulation of the cylindrical phantom closely reproduced the experimental data. These results suggest that GATE enables accurate simulation of (111)In SPECT acquisitions. PMID:15972984

  3. Selective platelet deposition during focal cerebral ischemia in the monkey

    SciTech Connect

    Feinberg, H.; Crowell, R.M.; Jafar, J.J.; Marmo, F.; Gandhi, Y.; Mosher, J.L.; Le Breton, G.C.

    1986-03-01

    Platelet thrombosis in the microcirculation may play a central role in focal cerebral ischemia. The authors investigated platelet deposition after temporary middle cerebral artery (MCA) occlusion in the monkey. Anesthetized monkeys were infused with autologous /sup 111/In-labeled platelets and /sup 51/Cr-labeled red cells in order to measure platelet deposition independent of hemorrhage. The right MCA was occluded for 6 hrs with a clip via a trans-orbital approach. Following clip removal, reperfusion was carried out for 45 min after which the animal was sacrificed. Brain samples were assayed for platelet deposition in selected areas of the right and left hemispheres (RH, LH). Net platelet deposition was determined from the excess /sup 111/In counts above that contained in blood (as determined by /sup 51/Cr counts). It was found that ischemia resulted in selective platelet deposition in the area of the occluded MCA, i.e. the RH versus the corresponding areas in the LH. Differences between the RH and the LH were found in the (1) caudate nucleus, (2) internal capsule and (3) putamen. The data suggest that focal ischemia is associated with the activation of platelets in the ischemic area.

  4. Hyperfine field at Mn in the intermetallic compound LaMnSi2 measured by PAC using 111Cd nuclear probe

    NASA Astrophysics Data System (ADS)

    Domienikan, C.; Bosch-Santos, B.; Cabrera Pasca, G. A.; Saxena, R. N.; Carbonari, A. W.

    2015-04-01

    Magnetic hyperfine field at Mn site has been measured in the orthorhombic intermetallic compound LaMnSi2 with PAC spectroscopy using radioactive 111In- 111Cd nuclear probe. Samples of LaMnSi2 were prepared by melting pure metallic components in stoichiometric proportion in an arc furnace under argon atmosphere. The samples were sealed in a quartz tube under helium atmosphere, annealed at 1000 °C for 60 h and quenched in water. Samples were analyzed with X-ray diffraction method. 111In was introduced in the samples by thermal diffusion at 1000 °C for 60 h. PAC measurements were carried out with a six BaF2 detector spectrometer at several temperatures between 50 K and 410 K. Results show well defined quadrupole and magnetic interactions at all temperatures. The magnetic hyperfine field (Bhf) measured at 50 K is 7.1(1) T. The temperature dependence of Bhf follows the normal Brillouin-like behavior expected for a simple ferromagnetic ordering. The ferromagnetic transition temperature (Tc) was determined to be 401(1) K.

  5. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  6. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments

    PubMed Central

    Eter, Wael A.; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-01-01

    Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - opt