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Sample records for 111in ibritumomab tiuxetan

  1. Logistics of therapy with the ibritumomab tiuxetan regimen

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the {sup 131}I or {sup 9}Y radionuclide to monoclonal antibodies against CD20. In clinical trials, {sup 9}Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligible patients, and delivering the imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation safety procedures to protect family members and healthcare professionals involved in the care of patients treated with {sup 9}Y ibritumomab tiuxetan are also reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard precautions needed to minimize radiation exposure to other persons.

  2. 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

  3. 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.

  4. 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

  5. Dynamic Metabolic Changes during the First 3 Months after 90Y-Ibritumomab Tiuxetan Radioimmunotherapy

    PubMed Central

    Koyama, Keitaro; Kurokawa, Mineo; Ohtomo, Kuni

    2014-01-01

    Objective. To elucidate the time course of tumor metabolism during the first 3 months after 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) in patients with refractory malignant lymphoma. Materials and Methods. Seven patients with recurrent follicular lymphoma underwent FDG-PET imaging before and after 1-, 4-, and 12-week RIT with 90Y-ibritumomab tiuxetan. Tumor metabolic activity on FDG-PET scans was assessed as the maximum standard uptake value (SUVmax). Results. Decrease in metabolism was detected 1 week after RIT. In the most decreased lesion, SUVmax decreased to 20% of the baseline value during the first week. Most lesions continued to decrease for up to 4 weeks. Some lesions showed increased metabolism from 4 to 12 weeks, while the level of FDG accumulations at 12 weeks was still lower than the baseline. Conclusions. Tumor response to RIT could be observed as early as 1 week after the administration of RIT. After tumor activity decreases, the metabolism may increase at least between 4 and 12 weeks. It suggests that the metabolic changes should be carefully evaluated during this period. PMID:25050390

  6. Efficacy of ⁹⁰Yttrium-ibritumomab tiuxetan in relapsed/refractory extranodal marginal-zone lymphoma.

    PubMed

    Vanazzi, Anna; Grana, Chiara; Crosta, Cristiano; Pruneri, Giancarlo; Rizzo, Stefania; Radice, Davide; Pinto, Antonello; Calabrese, Liliana; Paganelli, Giovanni; Martinelli, Giovanni

    2014-03-01

    We evaluated clinical activity of ⁹⁰Yttrium-ibritumomab (⁹⁰Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received ⁹⁰Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. ⁹⁰Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients.

  7. A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma.

    PubMed

    Witzig, Thomas E; Wiseman, Gregory A; Maurer, Matthew J; Habermann, Thomas M; Micallef, Ivana N M; Nowakowski, Grzegorz S; Ansell, Stephen M; Colgan, Joseph P; Inwards, David J; Porrata, Luis F; Link, Brian K; Zent, Clive S; Johnston, Patrick B; Shanafelt, Tait D; Allmer, Cristine; Asmann, Yan W; Gupta, Mamta; Ballas, Zuhair K; Smith, Brian J; Weiner, George J

    2013-07-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.

  8. A Phase I Trial of Immunostimulatory CpG 7909 Oligodeoxynucleotide and 90Yttrium Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed B-cell Non-Hodgkin Lymphoma

    PubMed Central

    Witzig, Thomas E.; Wiseman, Gregory A.; Maurer, Matthew J.; Habermann, Thomas M.; Micallef, Ivana N. M.; Nowakowski, Grzegorz S.; Ansell, Stephen M.; Colgan, Joseph P.; Inwards, David J.; Porrata, Luis F.; Link, Brian K.; Zent, Clive S.; Johnston, Patrick B.; Shanafelt, Tait D.; Allmer, Cristine; Asmann, Yan W.; Gupta, Mamta; Ballas, Zuhair K.; Smith, Brian J.; Weiner, George J.

    2014-01-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m2 days 1,8, and 15; 111In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of 90Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hours without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation. PMID:23619698

  9. Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

    PubMed

    Rossignol, J; Terriou, L; Robu, D; Willekens, C; Hivert, B; Pascal, L; Guieze, R; Trappe, R; Baillet, C; Huglo, D; Morschhauser, F

    2015-07-01

    Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

  10. 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

  11. Efficacy of 90Y ibritumomab-tiuxetan treatment in a case of resistant gastric MALT non-Hodgkin’s lymphoma

    PubMed Central

    Ferrucci, PF; Vanazzi, A; Crosta, C; Pruneri, G; Grana, C; Bartolomei, M; Paganelli, G; Martinelli, G

    2008-01-01

    Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin’s lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results. Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin (90Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches. PMID:22275968

  12. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma.

    PubMed

    Fruchart, Christophe; Tilly, Hervé; Morschhauser, Franck; Ghesquières, Hervé; Bouteloup, Marie; Fermé, Christophe; Van Den Neste, Eric; Bordessoule, Dominique; Bouabdallah, Reda; Delmer, Alain; Casasnovas, René Olivier; Ysebaert, Loïc; Ciappuccini, Renaud; Briere, Josette; Gisselbrecht, Christian

    2014-12-01

    We evaluated the safety and efficacy of standard-dose yttrium-90 (Y(90)) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y(90) ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y(90) ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y(90) ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.

  13. 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.

  14. Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology.

    PubMed

    Krishnan, Amrita Y; Palmer, Joycelynne; Nademanee, Auayporn P; Chen, Robert; Popplewell, Leslie L; Tsai, Ni-Chun; Sanchez, James F; Simpson, Jennifer; Spielberger, Ricardo; Yamauchi, Dave; Forman, Stephen J

    2017-03-04

    Standard-dose (90)yttrium-ibritumomab tiuxetan (.4 mci/kg) together with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) (Z-BEAM) has been shown to be a well-tolerated autologous hematopoietic stem cell transplantation preparative regimen for non-Hodgkin lymphoma. We report the outcomes of a single-center, single-arm phase II trial of Z-BEAM conditioning in high-risk CD20(+) non-Hodgkin lymphoma histologic strata: diffuse large B cell (DLBCL), mantle cell, follicular, and transformed. Robust overall survival and notably low nonrelapse mortality rates (.9% at day +100 for the entire cohort), with few short- and long-term toxicities, confirm the safety and tolerability of the regimen. In addition, despite a high proportion of induction failure patients (46%), the promising response and progression-free survival (PFS) rates seen in DLBCL (3-year PFS: 71%; 95% confidence interval, 55 to 82%), support the premise that the Z-BEAM regimen is particularly effective in this histologic subtype. The role of Z-BEAM in other strata is less clear in the context of the emergence of novel agents.

  15. Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

    PubMed

    Cabrero, Monica; Martin, Alejandro; Briones, Javier; Gayoso, Jorge; Jarque, Isidro; López, Javier; Grande, Carlos; Heras, Inmaculada; Arranz, Reyes; Bernal, Teresa; Perez-Lopez, Estefania; López-Godino, Oriana; Conde, Eulogio; Caballero, Dolores

    2017-01-01

    We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m(2) i.v. (days -3 and -2) plus melphalan 70 mg/m(2) i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.

  16. FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases

    PubMed Central

    2011-01-01

    Background This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. Methods The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m2x 3 days), C (1 gr/m2 day 1) and R (375 mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. Results Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. Conclusions Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by 90Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS. PMID:21303501

  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. 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

  19. 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.

  20. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14

    PubMed Central

    Hertzberg, Mark; Gandhi, Maher K.; Trotman, Judith; Butcher, Belinda; Taper, John; Johnston, Amanda; Gill, Devinder; Ho, Shir-Jing; Cull, Gavin; Fay, Keith; Chong, Geoff; Grigg, Andrew; Lewis, Ian D.; Milliken, Sam; Renwick, William; Hahn, Uwe; Filshie, Robin; Kannourakis, George; Watson, Anne-Marie; Warburton, Pauline; Wirth, Andrew; Seymour, John F.; Hofman, Michael S.; Hicks, Rodney J.

    2017-01-01

    In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results

  1. 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 ...

  2. 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

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

    ClinicalTrials.gov

    2016-12-20

    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

  4. 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

  5. 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

  6. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    PubMed

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for

  7. 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

    2017-01-04

    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

  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. 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.

  10. 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.

  11. 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

  12. Distribution and dosimetry of 111In-labeled platelets.

    PubMed

    Robertson, J S; Dewanjee, M K; Brown, M L; Fuster, V; Cesebro, J H

    1981-07-01

    The distribution of 111In-labeled platelets was studied in five young, healthy men. The radioactivity in the lungs, heart, liver, spleen, kidneys, and testes was determined from areas-of-interest in computed gamma-camera scans at intervals up to 75 hours after injection. After the first four hours, the activity in each organ studied except the liver and kidney decreased at roughly the physical decay rate. In the liver and kidney, the curves were relatively flat, indicating continued accumulation of the radiotracer. The calculated mean radiation absorbed dose per unit administered activity was 0.60 +/- 0.07 rad/mCi (0.16 +/- 0.02 Gy/GBq) for the total body, and was 34 +/- 6 rad/mCi (9.0 +/- 1.5 Gy/GBq) for the spleen.

  13. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    SciTech Connect

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  14. 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.

  15. 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.

  16. Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF in normal mice.

    PubMed

    Tolmachev, Vladimir; Orlova, Anna; Wei, Qichun; Bruskin, Alexander; Carlsson, Jörgen; Gedda, Lars

    2004-08-01

    EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of breast, lung, and urinary bladder. For this reason, EGFR may be an attractive target for both visualization and therapy of malignant tumors using radioactive nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53-amino-acid protein. Low molecular weight of EGF may enable better intratumoral penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the targeting of glioblastoma and breast cancer, and its tumor-seeking properties were confirmed in animal studies. The aim of this study was to evaluate how the substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice. [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl-DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours postinjection, the animals were sacrificed, and radioactivity in different organs was measured. The blood clearance of both conjugates was fast. The uptake of both conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary gland was most likely receptor-mediated. The uptake in a majority of organs was similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.

  17. 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.

  18. Preparation, cytotoxicity, and in vivo antitumor efficacy of 111In-labeled modular nanotransporters

    PubMed Central

    Slastnikova, Tatiana A; Rosenkranz, Andrey A; Morozova, Natalia B; Vorontsova, Maria S; Petriev, Vasiliy M; Lupanova, Tatiana N; Ulasov, Alexey V; Zalutsky, Michael R; Yakubovskaya, Raisa I; Sobolev, Alexander S

    2017-01-01

    Purpose Modular nanotransporters (MNTs) are a polyfunctional platform designed to achieve receptor-specific delivery of short-range therapeutics into the cell nucleus by receptor-mediated endocytosis, endosome escape, and targeted nuclear transport. This study evaluated the potential utility of the MNT platform in tandem with Auger electron emitting 111In for cancer therapy. Methods Three MNTs developed to target either melanocortin receptor-1 (MC1R), folate receptor (FR), or epidermal growth factor receptor (EGFR) that are overexpressed on cancer cells were modified with p-SCN-Bn-NOTA and then labeled with 111In in high specific activity. Cytotoxicity of the 111In-labeled MNTs was evaluated on cancer cell lines bearing the appropriate receptor target (FR: HeLa, SK-OV-3; EGFR: A431, U87MG.wtEGFR; and MC1R: B16-F1). In vivo micro-single-photon emission computed tomography/computed tomography imaging and antitumor efficacy studies were performed with intratumoral injection of MC1R-targeted 111In-labeled MNT in B16-F1 melanoma tumor-bearing mice. Results The three NOTA-MNT conjugates were labeled with a specific activity of 2.7 GBq/mg with nearly 100% yield, allowing use without subsequent purification. The cytotoxicity of 111In delivered by these MNTs was greatly enhanced on receptor-expressing cancer cells compared with 111In nontargeted control. In mice with B16-F1 tumors, prolonged retention of 111In by serial imaging and significant tumor growth delay (82% growth inhibition) were found. Conclusion The specific in vitro cytotoxicity, prolonged tumor retention, and therapeutic efficacy of MC1R-targeted 111In-NOTA–MNT suggest that this Auger electron emitting conjugate warrants further evaluation as a locally delivered radiotherapeutic, such as for ocular melanoma brachytherapy. Moreover, the high cytotoxicity observed with FR- and EGFR-targeted 111In-NOTA–MNT suggests further applications of the MNT delivery strategy should be explored. PMID:28138237

  19. 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.

  20. Distribution of DNA strand breaks produced by iodine-123 and indium-111 in synthetic oligodeoxynucleotides.

    PubMed

    Karamychev, V N; Reed, M W; Neumann, R D; Panyutin, I G

    2000-01-01

    Antigene radiotherapy, a procedure based on delivery of short-range Auger-electron-emitting radioisotopes to target genes via sequence-specific triplex-forming oligonucleotides, has been successfully demonstrated in vitro using the well-studied radionuclide 125I. To proceed with in vivo trials, Auger electron emitters with shorter half-lives than 125I are required. Here we report a study of the efficiency and distribution of sequence-specific DNA strand breaks produced by decay of 123I and mIIn. 123I and 111In were introduced into triplex-and duplex-forming oligodeoxyribonucleotides (ODNs) through carbohydrate linkers of various lengths. Labeling with radioiodine was performed through tributylstannylbenzamide intermediates while 111In was attached via DTPA. The Auger-emitter-labeled ODNs were hybridized to a single-stranded DNA target, to form duplexes. After decay accumulation, the target DNA samples were assayed for strand breaks using a sequencing gel-electrophoresis technique. For the first time, we observed footprints of DNA strand breaks produced by 123I and 111In. Most of the breaks were located within 10 nucleotides from the decay site. The yield of strand breaks per decay varies; decay of 111In breaks DNA almost 10 times more effectively than decay of 123I. Both 123I and 111In are less effective in breaking DNA strands than 121I, which reflects the higher total energy of the Auger decay process of 125I.

  1. Radioimmunodetection of cutaneous T-cell lymphoma with 111In-labeled T101 monoclonal antibody

    SciTech Connect

    Carrasquillo, J.A.; Bunn, P.A. Jr.; Keenan, A.M.; Reynolds, J.C.; Schroff, R.W.; Foon, K.A.; Su, M.H.; Gazdar, A.F.; Mulshine, J.L.; Oldham, R.K.

    1986-09-11

    T101 monoclonal antibody recognizes a pan-T-cell antigen present on normal T cells and also found in high concentrations in cutaneous T-cell lymphoma. We used this antibody, radiolabeled with 111In, in gamma-camera imaging to detect sites of metastatic cutaneous T-cell lymphoma in 11 patients with advanced disease. In all patients, (/sup 111/In)T101 concentrated in pathologically or clinically detected nodes, including those in several previously unsuspected nodal regions. Concentrations (per gram of tissue) ranged from 0.01 to 0.03 percent of the injected dose and were consistently 10 to 100 times higher than previously reported on radioimmunodetection. Focal uptake was seen in skin tumors and heavily infiltrated erythroderma but not in skin plaques. The specificity of tumor targeting was documented by control studies with (/sup 111/In)chloride or (/sup 111/In)9.2.27 (anti-melanoma) monoclonal antibody. Increasing the T101 dose (1 to 50 mg) altered distribution in nontumor tissues. These studies suggest that imaging with (/sup 111/In)T101 may be of value in identifying sites of cutaneous T-cell lymphoma. In contrast to the targeting of solid tumors, the mechanism of localization appears to be related to binding to T cells, which can then carry the radioactivity to involved sites.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Doppler-shift attenuation method lifetime measurements of low-lying states in 111In

    NASA Astrophysics Data System (ADS)

    Bucurescu, D.; Căta-Danil, I.; Ilaş, G.; Ivaşcu, M.; Mărginean, N.; Stroe, L.; Ur, C. A.

    1996-11-01

    The lifetimes of nine low-lying excited states in 111In have been measured with the Doppler-shift attenuation method in the 111Cd(p,nγ) reaction. A comparison of experimental quantities with predictions based on the interacting boson-fermion model unravels the states due to the coupling of a g9/2 proton hole to the quadrupole vibrations of the core.

  8. A case of bronchial carcinoid: diagnosis and follow-up with 111In-DTPA-octreotide.

    PubMed

    Orsolon, P; Bagni, B; Basadonna, P; Geatti, O; Talmassons, G; Guerra, U P

    1995-12-01

    Scintigraphy with radiolabelled analogue of somatostatin is highly sensitive in detecting carcinoid tumors especially if performed with Single Photon Computed Tomography (SPECT). In this report we describe our experience with 111In-DTPA-Octreotide in a female patient affected by a small asymptomatic intrabronchial carcinoid demonstrated by CT scan and bronchial endoscopy performed after recurrent left pneumonias. Planar views and SPECT images, using 111In-DTPA-Octreotide, were collected before and four hours after the first endoscopic laser resection. All groups of SPECT images were positive in the left parahilar region but at a different degree. Scans performed after resection showed a low degree of uptake which was considered to be probably secondary to local swelling; CT scan was negative. Follow up endoscopic biopsy repeated at six months, showed a relapse always in the same site; CT scan of the thorax was again negative. 111In-DTPA-Octreotide images obtained at twelve months were positive always in the left parahilar region, CT scan was negative but another biopsy was not possible. Therefore it was suspected a relapse of the carcinoid which was probably growing only through the bronchial wall without spreading towards the bronchial lumen and/or the lung parenchima. In this occasion, it was also thought that images collected four hours after resection could be positive not only for swelling but for a relapse as well. In every scintigraphic session, SPECT images presented higher quality than planar. This case suggests that 111In-DTPA-Octreotide SPECT is a non-invasive diagnostic technique which could be applied as a follow-up tool especially to patients with no-secreting carcinoid neoplasm and/or with negative or doubtful endoscopic and radiological investigations.

  9. 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.

  10. A comparison of 111In with 52Fe and 99mTc-sulfur colloid for bone marrow scanning.

    PubMed

    Merrick, M V; Gordon-Smith, E C; Lavender, J P; Szur, L

    1975-01-01

    Under most circumstances 52Fe, 111In, and colloid show a similar distribution of marrow. The lesser uptake of 111In by liver and spleen may occasionally be of value in permitting visualization of that portion of the spinal marrow obscured by these organs in the colloid scan. However, in red cell aplasia, when there is dissociation between phagocytic and erythropoietic functions, scanning with 111In gives no information about erythropoietic tissue distribution. Therefore, indium cannot be used as an analog for iron in the study of the hematopoietic system.

  11. 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.

  12. 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.

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

    PubMed

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

    2008-05-01

    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.

  14. 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).

  15. Radiation protection of staff in 111In radionuclide therapy--is the lead apron shielding effective?

    PubMed

    Lyra, M; Charalambatou, P; Sotiropoulos, M; Diamantopoulos, S

    2011-09-01

    (111)In (Eγ = 171-245 keV, t1/2 = 2.83 d) is used for targeted therapies of endocrine tumours. An average activity of 6.3 GBq is injected into the liver by catheterisation of the hepatic artery. This procedure is time-consuming (4-5 min) and as a result, both the physicians and the technical staff involved are subjected to radiation exposure. In this research, the efficiency of the use of lead apron has been studied as far as the radiation protection of the working staff is concerned. A solution of (111)In in a cylindrical scattering phantom was used as a source. Close to the scattering phantom, an anthropomorphic male Alderson RANDO phantom was positioned. Thermoluminescent dosemeters were located in triplets on the front surface, in the exit and in various depths in the 26th slice of the RANDO phantom. The experiment was repeated by covering the RANDO phantom by a lead apron 0.25 mm Pb equivalent. The unshielded dose rates and the shielded photon dose rates were measured. Calculations of dose rates by Monte Carlo N-particle transport code were compared with this study's measurements. A significant reduction of 65 % on surface dose was observed when using lead apron. A decrease of 30 % in the mean absorbed dose among the different depths of the 26th slice of the RANDO phantom has also been noticed. An accurate correlation of the experimental results with Monte Carlo simulation has been achieved.

  16. 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

  17. Radiolabeled (111)In-FGF-2 Is Suitable for In Vitro/Ex Vivo Evaluations and In Vivo Imaging.

    PubMed

    Moscaroli, Alessandra; Jones, Gabriel; Lühmann, Tessa; Meinel, Lorenz; Wälti, Stephanie; Blanc, Alain; Fischer, Eliane; Hilbert, Manuel; Schibli, Roger; Béhé, Martin

    2017-03-06

    Fibroblast growth factor-2 (FGF-2) is a potent modulator of cell growth and regulation, with improper FGF-2 signaling being involved in impaired responses to injury or even cancer. Therefore, the exploitation of FGF-2 as a therapeutic drives the prerequisite for effective insight into drug disposition kinetics. In this article, we present an (111)In-radiolabeled FGF-2 derivative for noninvasive imaging in small animals deploying single photon emission tomography (SPECT). (111)In-FGF-2 is equally well suitable for in vitro and ex vivo investigations as (125)I-FGF-2. Furthermore, (111)In-FGF-2 permits the performance of in vivo imaging, for example for the analysis of FGF-2 containing pharmaceutical formulations in developmental or preclinical stages. (111)In-FGF-2 had affinity for the low-molecular-weight heparin enoxaparin identical to that of unlabeled FGF-2 (Kd: 0.6 ± 0.07 μM and 0.33 ± 0.03 μM, respectively) as assessed by isothermal titration calorimetry. The binding of (111)In-FGF-2 to heparan sulfate proteoglycans (HPSGs) and the biological activity were comparable to those of unlabeled FGF-2, with EC50 values of 12 ± 2 pM and 25 ± 6 pM, respectively. In vivo biodistribution in healthy nude mice indicated a predominant accumulation of (111)In-FGF-2 in filtering organs and minor uptake in the retina and the salivary and pituitary glands, which was confirmed by SPECT imaging. Therefore, (111)In-FGF-2 is a valid tracer for future noninvasive animal imaging of FGF-2 in pharmaceutical development.

  18. 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

  19. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    PubMed

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT.

  20. 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.

  1. Experimental study of {Delta}I=1 bands in {sup 111}In

    SciTech Connect

    Banerjee, P.; Pradhan, M. K.; Ganguly, S.; Sharma, H. P.; Muralithar, S.; Singh, R. P.; Bhowmik, R. K.

    2011-02-15

    The two {Delta}I=1 bands in {sup 111}In, built upon the 3461.0 and 4931.8 keV states, have been studied. The bands were populated in the reaction {sup 100}Mo({sup 19}F, {alpha}4n{gamma}) at a beam energy of 105 MeV. Mean lifetimes of nine states, four in the first and five in the second band, have been determined for the first time from Doppler shift attenuation data. The deduced B(M1) rates and their behavior as a function of level spin support the interpretation of these bands within the framework of the shears mechanism. The geometrical model of Machiavelli et al. has been used to derive the effective gyromagnetic ratios for the two bands.

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

    PubMed

    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 (111)In-labeled human internalizing antibody, INCA-X ((111)In-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 (111)In-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 (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-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 (111)In-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.

  3. 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.

  4. 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.

  5. Size dependent biodistribution and SPECT imaging of (111)In-labeled polymersomes.

    PubMed

    Brinkhuis, René P; Stojanov, Katica; Laverman, Peter; Eilander, Jos; Zuhorn, Inge S; Rutjes, Floris P J T; van Hest, Jan C M

    2012-05-16

    Polymersomes, self-assembled from the block copolymer polybutadiene-block-poly(ethylene glycol), were prepared with well-defined diameters between 90 and 250 nm. The presence of ~1% of diethylene triamine penta acetic acid on the polymersome periphery allowed to chelate radioactive (111)In onto the surface and determine the biodistribution in mice as a function of both the polymersome size and poly(ethylene glycol) corona thickness (i.e., PEG molecular weight). Doubling the PEG molecular weight from 1 kg/mol to 2 kg/mol did not change the blood circulation half-life significantly. However, the size of the different polymersome samples did have a drastic effect on the blood circulation times. It was found that polymersomes of 120 nm and larger become mostly cleared from the blood within 4 h, presumably due to recognition by the reticuloendothelial system. In contrast, smaller polymersomes of around 90 nm circulated much longer. After 24 h more than 30% of the injected dose was still present in the blood pool. This sharp transition in blood circulation kinetics due to size is much more abrupt than observed for liposomes and was additionally visualized by SPECT/CT imaging. These findings should be considered in the formulation and design of polymersomes for biomedical applications. Size, much more than for liposomes, will influence the pharmacokinetics, and therefore, long circulating preparations should be well below 100 nm.

  6. 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.

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

    PubMed

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

    2005-10-07

    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 5x10(6) 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: 128x128 matrix with 128 projections over 360 degrees) 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.

  8. 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.

  9. Detection of acute inflammation with /sup 111/In-labeled nonspecific polyclonal IgG

    SciTech Connect

    Fischman, A.J.; Rubin, R.H.; Khaw, B.A.; Callahan, R.J.; Wilkinson, R.; Keech, F.; Nedelman, M.; Dragotakes, S.; Kramer, P.B.; LaMuraglia, G.M.

    1988-10-01

    The detection of focal sites of inflammation is an integral part of the clinical evaluation of the febrile patient. When anatomically distinct abscesses are present, lesion detection can be accomplished by standard radiographic techniques, particularly in patients with normal anatomy. At the phlegmon stage, however, and in patients who have undergone surgery, these techniques are considerably less effective. While radionuclide methods, such as Gallium-67 (67Ga)-citrate and Indium-111 (111In)-labeled WBCs have been relatively successful for the detection of early inflammation, neither approach is ideal. In the course of studies addressing the use of specific organism-directed antibodies for imaging experimental infections in animals, we observed that nonspecific polyclonal immunoglobulin G (IgG) localized as well as specific antibodies. Preliminary experiments suggested that the Fc portion of IgG is necessary for effective inflammation localization. Since polyclonal IgG in gram quantities has been safely used for therapy in patients with immune deficiency states, we decided to test whether milligram quantities of radiolabeled IgG could image focal sites of inflammation in humans. Thus far, we have studied a series of 84 patients with suspected lesions in the abdomen, pelvis, vascular grafts, lungs, or bones/joints. In 48 of 52 patients with focal lesions detected by surgery, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US), the IgG scan correctly localized the site, while 31 patients without focal inflammation had no abnormal focal localization of the radiopharmaceutical. Four patients had false negative scans and one patient had a false positive scan. For this small series, the overall sensitivity and specificity were 92% and 95%, respectively. In this report, we review our experience with this exciting new agent.

  10. Technical considerations in the study of /sup 111/In-oxine labelled platelet survival patterns in dogs

    SciTech Connect

    Sharefkin, J.; Rich, N.M.

    1982-04-01

    A detailed technique for labelling canine platelets with /sup 111/In-oxine for the study of platelet survival patterns in four to six dogs at a time was developed. Useful modifications of earlier methods included splitting of the platelet rich plasma into multiple aliquots to improve pelleting efficiency at low gravity forces, use of saved platelet poor plasma to flush out injection syringes, and prompt use of commercial /sup 111/In-oxine sources 3 to 5 minutes after mixing with Ringer's Citrate Dextrose. Avoidable pitfalls of the method included excessive lengths of incubation time in plasma free medium and loss of labelling efficacy by exposure of the chelate to iron or other metal contaminants in glassware. The method was used to study changes in platelet survival time in dogs with large synthetic arterial prostheses, and gave results in good agreement with earlier studies using /sup 51/Cr labelled platelets.

  11. Direct intralymphatic injection of radiolabeled sup 111 In-T101 in patients with cutaneous T-cell lymphoma

    SciTech Connect

    Mulshine, J.L.; Carrasquillo, J.A.; Weinstein, J.N.; Keenan, A.M.; Reynolds, J.C.; Herdt, J.; Bunn, P.A.; Sausville, E.; Eddy, J.; Cotelingam, J.D. )

    1991-01-15

    Direct intralymphatic administration of radiolabeled monoclonal antibody in targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing staging lymphangiography received intralymphatic infusions of {sup 111}In-T101 to evaluate lymph node involvement. This procedure was accomplished without significant complication. The {sup 111}In-T101 rapidly distributed throughout the regional lymphatic compartment and passed into the systemic circulation. Tumor-bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of the injected dose of radiolabeled antibody. Three patients were upstaged to Stage IVA based on tumor involvement found after radiolymphoscintigraphy-directed biopsy of groin lymph nodes, selected because of intense radioactivity by gamma camera imaging. Compared with previously reported s.c. antibody administration, there was a marked reduction in the radioactive exposure of normal tissues at the injection sites in the lower extremities. Direct intralymphatic delivery of {sup 111}In-T101 appears to be a feasible, efficient method for delivering therapeutic doses of radiolabeled antibody.

  12. [111In-DOTA]Somatostatin-14 analogs as potential pansomatostatin-like radiotracers - first results of a preclinical study

    PubMed Central

    2012-01-01

    Background In this study, we report on the synthesis, radiolabeling, and biological evaluation of two new somatostatin-14 (SS14) analogs, modified with the universal chelator DOTA. We were interested to investigate if and to what extent such radiotracer prototypes may be useful for targeting sst1-5-expressing tumors in man but, most importantly, to outline potential drawbacks and benefits associated with their use. Methods AT1S and AT2S (DOTA-Ala1-Gly2-c[Cys3-Lys4-Asn5-Phe6-Phe7-Trp8/DTrp8-Lys9-Thr10-Phe11-Thr12-Ser13-Cys14-OH], respectively) were synthesized on the solid support and labeled with 111In. The sst1-5 affinity profile of AT1S/AT2S was determined by receptor autoradiography using [Leu8,dTrp22,125I-Tyr25]SS28 as radioligand. The ability of AT2S to stimulate sst2 or sst3 internalization was qualitatively analyzed by an immunofluorescence-based internalization assay using hsst2- or hsst3-expressing HEK293 cells. Furthermore, the internalization of the radioligands [111In]AT1S and [111In]AT2S was studied at 37 °C in AR4-2J cells endogenously expressing sst2. The in vivo stability of [111In]AT1S and [111In]AT2S was tested by high-performance liquid chromatography analysis of mouse blood collected 5 min after radioligand injection, and biodistribution was studied in normal mice. Selectively for [111In]AT2S, biodistribution was further studied in SCID mice bearing AR4-2J, HEK293-hsst2A+, -hsst3+ or -hsst5+ tumors. Results The new SS14-derived analogs were obtained by solid phase peptide synthesis and were easily labeled with 111In. Both SS14 conjugates, AT1S, and its DTrp8 counterpart, AT2S, showed a pansomatostatin affinity profile with the respective hsst1-5 IC50 values in the lower nanomolar range. In addition, AT2S behaved as an agonist for sst2 and sst3 since it stimulated receptor internalization. The 111In radioligands effectively and specifically internalized into rsst2A-expressing AR4-2J cells with [111In]AT2S internalizing faster than [111In]AT1

  13. 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

  14. Quantitative in situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide

    DTIC Science & Technology

    2007-05-01

    Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide PRINCIPAL INVESTIGATOR: Gina G...Quantitative in situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide 5b. GRANT NUMBER...Somatostatin (SST) is a peptide hormone implicated in the growth and progression of cancers and SSTR2 is the predominant receptor subtype expressed in

  15. 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.

  16. Underpotential deposition of hydrogen on benzene-modified Pt(111) in aqueous H2SO4.

    PubMed

    Jerkiewicz, Gregory; DeBlois, Martin; Radovic-Hrapovic, Zorana; Tessier, Jean-Pierre; Perreault, Frédéric; Lessard, Jean

    2005-04-12

    The Pt(111) electrode is modified by an overlayer of C6H6 (ads) upon its cycling in the 0.05-0.80 V range in aq H2SO4 + 1 mM C6H6. The C6H6 (ads) overlayer significantly changes the underpotential-deposited H (H(UPD)) and anion adsorption, and cyclic-voltammetry (CV) profiles show a sharp cathodic peak and an asymmetric anodic one in the 0.05-0.80 V potential range. The C6H6 (ads) layer blocks the (bi)sulfate adsorption but facilitates the adsorption of one monolayer of H(UPD). Cycling of the benzene-modified Pt(111) in benzene-free aq 0.05 H2SO4 from 0.05 to 0.80 V results in a partial desorption of C6H6 (ads) and in a partial recovery of the CV profile characteristic of an unmodified Pt(111). The peak potential of the cathodic and anodic feature is independent of the scan rate, s (10 < or = s < or = 100 mV s(-1)), and the peak current density increases linearly with an increase of the scan rate. Temperature variation modifies the peak potential and current density but does not affect the charge density of the cathodic or anodic feature. Temperature-dependent studies allow us to determine the thermodynamic state function for the H(UPD) adsorption and desorption. Delta G degrees(ads)(H(UPD))assumes values from -4 to -12 kJ mol(-1), while has values from 9 to 14 kJ mol(-1). The values of delta Delta G degrees (delta Delta G degrees = delat Delta G degrees(ads) + delta Delta D degrees(des)) decrease almost linearly from 6 kJ mol(-1) at theta(H(UPD) --> 0 to 0 kJ mol(-1) at theta(H(UPD) --> 1. The nonzero values of delta Delta G degrees testify that the adsorbing and desorbing H(UPD) adatoms interact with an energetically different substrate. The lateral interactions changed from repulsive (omega = 29 kJ mol(-1) at theta(H(UPD) --> 0) to attractive (omega = -28 kJ mol(-1) at theta(H(UPD) --> 1) as the H(UPD) coverage increases. The values of delta S degrees(ads)(H(UPD)) increase from 19 to 56 J K(-1) mol(-1), while those of delta S degrees(des)(H(UPD)) decrease from

  17. Structural Stability and Phase Transitions of Octanethiol Self-Assembled Monolayers on Au(111) in Ultrahigh Vacuum.

    PubMed

    Lee, Nam-Suk; Cho, Gyoujin; Shin, Hoon-Kyu; Noh, Jaegeun

    2016-06-01

    To understand the structural stability of as-prepared octanethiol (OT) self-assembled monolayers (SAMs) with a fully covered c(4 x 2) phase on Au(111) in ultrahigh vacuum (UHV) conditions of 3 x 10(-7) Pa at room temperature, we examined OT SAM samples obtained as a function of storage period using scanning tunneling microscopy (STM). STM imaging revealed that phase transition of OT SAMs after storage in UHV for 3 days occurs from the c(4 x 2) phase to the mixed phase containing ordered c(4 x 2) and disordered phases. It was also observed that the disordered phase was mainly located at around vacancy islands and near step edges of Au(111) terraces, implying that desorption of OT molecules chemisorbed on Au(111) in UHV occurs more quickly in these regions compared with in the closely packed and ordered domains. After a longer storage in UHV for 6 days, OT SAMs with the c(4 x 2) phase were changed to the disordered phase containing a partially ordered domain with a row structure. From this study, we clearly demonstrated that OT molecules in SAMs on Au(111) are desorbed spontaneously in UHV at room temperature, resulting in the formation of disordered and row phases.

  18. Detection of primary breast cancer presenting as metastatic carcinoma of unknown primary origin by 111In-pentetreotide scan.

    PubMed

    Lenzi, R; Kim, E E; Raber, M N; Abbruzzese, J L

    1998-02-01

    Women with isolated metastatic carcinoma or adenocarcinoma involving axillary lymph nodes are a well-recognized group of unknown primary carcinoma (UPC) patients with a favorable prognosis. This group of patients are generally treated based on the assumption that they have occult breast cancer. However, to facilitate patient access to the whole spectrum of therapies available for patients with breast cancer, including strategies involving the use of high-dose chemotherapy, a precise diagnosis is increasingly important. In this clinical case we report the detection of a primary breast cancer by 111In-pentetreotide scanning in a woman who presented with metastatic carcinoma in axillary nodes, no palpable breast lesion, a nondiagnostic mammogram, and negative breast ultrasonography. Previous outcomes analysis of patients with UPC have emphasized the value of identifying women with breast cancer. This report suggests that the 111In-pentetreotide scan can contribute specific, clinically useful information in the evaluation of women presenting with metastatic carcinoma in axillary nodes and an occult primary and deserves prospective study in women with UPC presenting with isolated axillary metastases.

  19. The effect of ibuprofen on accumulation of /sup 111/In-labeled platelets and leukocytes in experimental myocardial infarction

    SciTech Connect

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schork, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-11-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (/sup 111/In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p . 0.005). Quantification of the platelet-associated /sup 111/In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.

  20. Description of a multicompartmental model of the biodistribution of 111In-DTPA-D-Phe-1-octreotide in human.

    PubMed

    D'addabbo, A; Simeone, G; Rubini, G; Nitti, L

    1995-12-01

    The aim of this study was to use compartmental analysis as a theoretical tool to provide quantitative and unitary data for a more precise determination of 111In-OCT concentrations in a tumour site and various body organs. Five subjects (3 male and 2 female) with neoplasias were studied. Structural and parametric identification of the model was based on the plasma, urine, total body and ROI (soft tissue, spleen, kidney and tumour) activity values. The model was of the mammillary type with 5 compartments (blood, soft tissue, spleen, kidneys and urine) for the 4 patients with a negative scintiscan and 6 (blood, soft tissue, spleen, kidneys, urine and tumour) for the adenocarcinoma patient. Numerical constants were determined by running a best-fit procedure with the MINUIT minimisation program (CERN library) using a microVAX 3800 computer. The reliability of the models was also tested. 111In-OCT accumulates in the kidneys and spleen, from which it is slowly released into the blood. Elimination is via the urine at first rapidly, then more slowly. The maximum concentration in the tumour compartment is reached at 12-14 hours and remains almost constant.

  1. Somatostatin receptor imaging with (111)In-pentetreotide in gastro-intestinal tract and lung neuroendocrine tumors-Impact on targeted treatment.

    PubMed

    Gerasimou, George; Moralidis, Efstratios; Gotzamani-Psarrakou, Anna

    2010-01-01

    Somatostatin is a neuropeptide that confers a wide range of pharmacological properties. Indium-111-tagged pentetreotide ((111)In-P) is a radiolabeled analogue of somatostatin indicated for the in vivo scintigraphic localization of neuroendocrine tumors (NET). In cases of NET of the gastro-intestinal tract we describe the sensitivity compared to conventional anatomical imaging modalities and especially the possibility that (111)In-P may change therapeutic management into up one fourth of the patients. In cases of small cell lung carcinoma it has been used for the evaluation of somatostatin receptor status and a substantial tool for differentiation between limited and extensive disease, especially when combined with anatomical imaging methods. We also describe the radiolabeled with yttrium-90 or lutetium-177 somatostatin analogue peptides in the treatment of NET and also the use of (111)In-P for the selection of patients for targeted treatment.

  2. /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.

  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. Stereochemistry of amino acid spacers determines the pharmacokinetics of (111)In-DOTA-minigastrin analogues for targeting the CCK2/gastrin receptor.

    PubMed

    Kolenc Peitl, Petra; Tamma, MariaLuisa; Kroselj, Marko; Braun, Friederike; Waser, Beatrice; Reubi, Jean Claude; Sollner Dolenc, Marija; Maecke, Helmut R; Mansi, Rosalba

    2015-06-17

    The metabolic instability and high kidney retention of minigastrin (MG) analogues hamper their suitability for use in peptide-receptor radionuclide therapy of CCK2/gastrin receptor-expressing tumors. High kidney retention has been related to N-terminal glutamic acids and can be substantially reduced by coinjection of polyglutamic acids or gelofusine. The aim of the present study was to investigate the influence of the stereochemistry of the N-terminal amino acid spacer on the enzymatic stability and pharmacokinetics of (111)In-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-D) and (111)In-DOTA-(l-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 ((111)In-PP11-L). Using circular dichroism measurements, we demonstrate the important role of secondary structure on the pharmacokinetics of the two MG analogues. The higher in vitro serum stability together with the improved tumor-to-kidney ratio of the (d-Glu)6 congener indicates that this MG analogue might be a good candidate for further clinical study.

  5. 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.

  6. 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.

  7. Mechanism of oxygen reduction reaction on Pt(111) in alkaline solution: Importance of chemisorbed water on surface

    DOE PAGES

    Liu, Shizhong; White, Michael G.; Liu, Ping

    2016-06-30

    Here, we report a detailed mechanistic study of the oxygen reduction reaction (ORR) on Pt(111) in alkaline solution, combining density functional theory and kinetic Monte Carlo simulations. A complex reaction network including four possible pathways via either 2e– or 4e– transfer is established and is able to reproduce the experimental measured polarization curve at both low- and high-potential regions. Our results show that it is essential to account for solvation by water and the dynamic coverage of *OH to describe the reaction kinetics well. In addition, a chemisorbed water (*H2O)-mediated mechanism including 4e– transfers is identified, where the reduction stepsmore » via *H2O on the surface are potential-independent and only the final removal of *OH from the surface in the form of OH–(aq) contributes to the current. For the ORR in alkaline solutions, such a mechanism is more competitive than the associative and dissociative mechanisms typically used to describe the ORR in acid solution. Finally, *OH and **O2 intermediates are found to be critically important for tuning the ORR activity of Pt in alkaline solution. To enhance the activity, the binding of Pt should be tuned in such a way that *OH binding is weak enough to release more surface sites under working conditions, while **O2 binding is strong enough to enable the ORR via the 4e– transfer mechanism.« less

  8. Targeting human prostate cancer with 111In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts.

    PubMed

    Lütje, Susanne; van Rij, Catharina M; Franssen, Gerben M; Fracasso, Giulio; Helfrich, Wijnand; Eek, Annemarie; Oyen, Wim J; Colombatti, Marco; Boerman, Otto C

    2015-01-01

    D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab')2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with (111)In-D2B IgG, (111)In-capromab pendetide, (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments in mice with PSMA-expressing LNCaP and PSMA-negative PC3 tumors at several time points after injection. All (111)In-labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of (111)In-D2B IgG and (111)In-capromab pendetide at 168 h p.i. (94.8 ± 19.2% injected dose per gram (ID/g) and 16.7 ± 2.2% ID/g, respectively), whereas uptake of (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments peaked at 24 h p.i. (12.1 ± 3.0% ID/g and 15.1 ± 2.9% ID/g, respectively). Maximum LNCaP tumor-to-blood ratios were 13.0 ± 2.3 (168 h p.i.), 6.2 ± 0.7 (24 h p.i.), 23.0 ± 4.0 (24 h p.i.) and 4.5 ± 0.6 (168 h p.i.) for (111)In-D2B IgG, (111)In-F(ab')2, (111)In-Fab and (111)In-capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab')2 and Fab fragments for targeting PSMA-expressing prostate cancer xenografts.

  9. Mechanism of oxygen reduction reaction on Pt(111) in alkaline solution: Importance of chemisorbed water on surface

    SciTech Connect

    Liu, Shizhong; White, Michael G.; Liu, Ping

    2016-06-30

    Here, we report a detailed mechanistic study of the oxygen reduction reaction (ORR) on Pt(111) in alkaline solution, combining density functional theory and kinetic Monte Carlo simulations. A complex reaction network including four possible pathways via either 2e or 4e transfer is established and is able to reproduce the experimental measured polarization curve at both low- and high-potential regions. Our results show that it is essential to account for solvation by water and the dynamic coverage of *OH to describe the reaction kinetics well. In addition, a chemisorbed water (*H2O)-mediated mechanism including 4e transfers is identified, where the reduction steps via *H2O on the surface are potential-independent and only the final removal of *OH from the surface in the form of OH(aq) contributes to the current. For the ORR in alkaline solutions, such a mechanism is more competitive than the associative and dissociative mechanisms typically used to describe the ORR in acid solution. Finally, *OH and **O2 intermediates are found to be critically important for tuning the ORR activity of Pt in alkaline solution. To enhance the activity, the binding of Pt should be tuned in such a way that *OH binding is weak enough to release more surface sites under working conditions, while **O2 binding is strong enough to enable the ORR via the 4e transfer mechanism.

  10. Recurrent pneumonia due to bronchial carcinoid tumour in a young patient: the role of (111)in-pentetreotide in imaging studies.

    PubMed

    García-Talavera, Paloma; López-Pedreira, María Rosa; Udaondo, Marian; Matilla, José María; Villanueva, Juan Gabriel; Borrego, Henar

    2015-03-01

    Bronchial carcinoid tumours are an uncommon cause of recurrent pneumonia in young patients. Diagnosis is determined from imaging studies, bronchoscopy, and histological confirmation, and treatment is generally surgical. Two cases are reviewed in order to examine the value of (111)In-DTPA-Phe-octreotide ((111)In-pentetreotide) scintigraphy in the pre-surgical evaluation of these patients. After a suspicious area was observed in other tests (standard X-ray, CT), a neuroendocrine tumour was diagnosed using this technique and the presence of regional or distant disease was ruled out. Comparison with the less valuable (18)F-FDG PET (carried out in one of the cases) highlights the usefulness of SPECT-CT, which performs notably better in terms of the localization and characterisation of findings.

  11. 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).

  12. Quantitative in Situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy With 111-in-Penetreotide

    DTIC Science & Technology

    2006-05-01

    Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide PRINCIPAL INVESTIGATOR: Gina G...31 Mar 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Quantitative in situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess...Somatostatin (SST) is a peptide hormone implicated in the growth and progression of cancers and SSTR2 is the predominant receptor subtype expressed

  13. 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.

  14. Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies.

    PubMed

    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 (90)Y-ibritumomab tiuxetan (Zevalin) and (131)I-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.

  15. Ongoing investigations and new uses of radioimmunotherapy in the treatment of non-Hodgkin's lymphoma

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.

  16. 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

  17. Optimization of IGF-1R SPECT/CT imaging using 111In-labeled F(ab')2 and Fab fragments of the monoclonal antibody R1507.

    PubMed

    Heskamp, Sandra; van Laarhoven, Hanneke W M; Molkenboer-Kuenen, Janneke D M; Bouwman, Wilbert H; van der Graaf, Winette T A; Oyen, Wim J G; Boerman, Otto C

    2012-08-06

    The insulin-like growth factor 1 receptor (IGF-1R) is a potential new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. IGF-1R expression can be visualized using radiolabeled R1507, a monoclonal antibody directed against IGF-1R. However, antibodies clear slowly from the circulation, resulting in low tumor-to-background ratios early after injection. Therefore, we aimed to accelerate targeting of IGF-1R using radiolabeled R1507 F(ab')2 and Fab fragments. In vitro, immunoreactivity, binding affinity and internalization of R1507 IgG, F(ab')2 and Fab were determined using the triple negative IGF-1R-expressing breast cancer cell line SUM149. In vivo, pharmacokinetics of (111)In-labeled R1507 IgG, F(ab')2 and Fab were studied in mice bearing subcutaneous SUM149 xenografts. SPECT/CT images were acquired and the biodistribution was measured ex vivo. The in vitro binding characteristics of radiolabeled R1507 IgG and F(ab')2 were comparable, whereas the affinity of Fab fragments was significantly lower (Kd: 0.6 nM, 0.7 nM and 3.0 nM for R1507 IgG, F(ab')2 and Fab, respectively). Biodistribution studies showed that the maximum tumor uptake of (111)In-R1507 IgG, F(ab')2 and Fab was 31.8% ID/g (72 h p.i.), 10.0% ID/g (6 h p.i.), and 1.8% ID/g (1 h p.i.), respectively. However, maximal tumor-to-blood ratios for F(ab')2 (24 h p.i.: 7.5) were more than twice as high as those obtained with R1507 (72 h p.i.: 2.8) and Fab (6 h p.i.: 2.8). Injection of an excess of unlabeled R1507 significantly reduced tumor uptake, suggesting that the uptake of R1507 IgG and F(ab')2 was specific for IGF-1R, while the major fraction of the tumor uptake of Fab was nonspecific. IGF-1R-expressing xenografts were visualized with (111)In-F(ab')2 SPECT/CT as early as 6 h p.i., while with R1507 IgG, the tumor could be visualized after 24 h. No specific targeting was observed with (111)In-Fab. (111)In

  18. Uptake of 111In-labeled fully human monoclonal antibody TSP-A18 reflects transferrin receptor expression in normal organs and tissues of mice.

    PubMed

    Sugyo, Aya; Tsuji, Atsushi B; Sudo, Hitomi; Nomura, Fumiko; Satoh, Hirokazu; Koizumi, Mitsuru; Kurosawa, Gene; Kurosawa, Yoshikazu; Saga, Tsuneo

    2017-03-01

    Transferrin receptor (TfR) is an attractive molecule for targeted therapy of cancer. Various TfR-targeted therapeutic agents such as anti-TfR antibodies conjugated with anticancer agents have been developed. An antibody that recognizes both human and murine TfR is needed to predict the toxicity of antibody-based agents before clinical trials, there is no such antibody to date. In this study, a new fully human monoclonal antibody TSP-A18 that recognizes both human and murine TfR was developed and the correlation analysis of the radiolabeled antibody uptake and TfR expression in two murine strains was conducted. TSP-A18 was selected using extracellular portions of human and murine TfR from a human antibody library. The cross-reactivity of TSP-A18 with human and murine cells was confirmed by flow cytometry. Cell binding and competitive inhibition assays with [111In]TSP-A18 showed that TSP-A18 bound highly to TfR-expressing MIAPaCa-2 cells with high affinity. Biodistribution studies of [111In]TSP-A18 and [67Ga]citrate (a transferrin-mediated imaging probe) were conducted in C57BL/6J and BALB/c-nu/nu mice. [111In]TSP-A18 was accumulated highly in the spleen and bone containing marrow component of both strains, whereas high [67Ga]citrate uptake was only observed in bone containing marrow component and not in the spleen. Western blotting indicated the spleen showed the strongest TfR expression compared with other organs in both strains. There was significant correlation between [111In]TSP-A18 uptake and TfR protein expression in both strains, whereas there was significant correlation of [67Ga]citrate uptake with TfR expression only in C57BL/6J. These findings suggest that the difference in TfR expression between murine strains should be carefully considered when testing for the toxicity of anti-TfR antibody in mice and the uptake of anti-TfR antibody could reflect tissue TfR expression more accurately compared with that of transferrin-mediated imaging probe such as [67Ga]citrate.

  19. The structure of the underpotential deposition of copper on to Pt(111) in the presence of chloride anions: a LEED structure analysis

    NASA Astrophysics Data System (ADS)

    Bludau, H.; Wu, K.; Zei, M. S.; Eiswirth, M.; Over, H.; Ertl, G.

    1998-05-01

    The underpotential deposition (UPD) of copper on to Pt(111) in the presence of chloride anions was studied by full-dynamical LEED-intensity analyses. A deformed (4×4) LEED pattern was observed at an emersion potential of 0.36 V vs. Ag/AgCl, right in between the two characteristic and well-separated peaks of the cyclic voltammogram (CV). Corresponding LEED intensity measurements and simulations of the integral-order beams indicate that the UPD of Cu forms a single pseudomorphic Cu layer on Pt(111).

  20. 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

    2016-04-04

    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

  1. 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.

  2. Synthesis and opioid receptor binding of indium (III) and [(111)In]-labeled macrocyclic conjugates of diprenorphine: novel ligands designed for imaging studies of peripheral opioid receptors.

    PubMed

    Srivastava, Shefali; Fergason-Cantrell, Emily A; Nahas, Roger I; Lever, John R

    2016-10-06

    Radiolabeled diprenorphine (DPN) and analogs are widely used ligands for non-invasive brain imaging of opioid receptors. To develop complementary radioligands optimized for studies of the peripheral opioid receptors, we prepared a pair of hydrophilic DPN derivatives, conjugated to the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), for complexation with trivalent metals. The non-radioactive indium (III) complexes, tethered to the C6-oxygen position of the DPN scaffold by 6- to 9-atom spacers, displayed high affinities for binding to μ, δ and κ opioid receptors in vitro. Use of the 9-atom linker conferred picomolar affinities equipotent to those of the parent ligand DPN. The [(111)In]-labeled complexes were prepared in good yield (>70%), with high radiochemical purity (~99%) and high specific radioactivity (>4000 mCi/μmol). Their log D7.4 values were -2.21 to -1.66. In comparison, DPN is lipophilic, with a log D7.4 of +2.25. Further study in vivo is warranted to assess the suitability of these [(111)In]-labeled DPN-DOTA conjugates for imaging trials.

  3. 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.

  4. 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.

  5. 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.

  6. Carbon 1s photoemission line analysis of C-based adsorbate on (111)In2O3 surface: The influence of reducing and oxidizing conditions

    NASA Astrophysics Data System (ADS)

    Brinzari, V.; Cho, B. K.; Korotcenkov, G.

    2016-12-01

    Synchrotron radiation photoemission study of C 1s line of (111) In2O3 surface was carried out under HV (high vacuum) doses of oxygen, carbon monoxide and water. Gas interaction with the surface was activated by heating of In2O3 monocrystalline film at temperatures of 160 or 250 °C. The study of complex structure of C 1 s line and evolution of its fine components allowed to establish their nature and to propose possible surface adsorbed species and reactions, including a direct chemisorption and dissociation of CO molecules. Reduction or oxidation of the surface determines whether the first (chemisorption) or the second (dissociation) process takes place. The latter is responsible for additional formation of ionosorbed oxygen. Both processes have not been previously reported for In2O3 and for conductive metal oxides.

  7. 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

  8. Influence of macrocyclic chelators on the targeting properties of (68)Ga-labeled synthetic affibody molecules: comparison with (111)In-labeled counterparts.

    PubMed

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

    2013-01-01

    Affibody molecules are a class of small (7 kDa) non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET) would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide (68)Ga (T1/2=67.6 min). Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) and 1-(1,3-carboxypropyl)-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA) were conjugated to the N-terminus of the synthetic Affibody molecule ZHER2:S1 targeting HER2. Affibody molecules were labeled with (68)Ga, and their binding specificity and cellular processing were evaluated. The biodistribution of (68)Ga-DOTA-ZHER2:S1, (68)Ga-NOTA-ZHER2:S1 and (68)Ga-NODAGA-ZHER2:S1, as well as that of their (111)In-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for (68)Ga-DOTA-ZHER2:S1 (17.9 ± 0.7%IA/g) was significantly higher than for both (68)Ga-NODAGA-ZHER2:S1 (16.13 ± 0.67%IA/g) and (68)Ga-NOTA-ZHER2:S1 (13 ± 3%IA/g) at 2 h after injection. (68)Ga-NODAGA-ZHER2:S1 had the highest tumor-to-blood ratio (60 ± 10) in comparison with both (68)Ga-DOTA-ZHER2:S1 (28 ± 4) and (68)Ga-NOTA-ZHER2:S1 (42 ± 11). The tumor-to-liver ratio was also higher for (68)Ga-NODAGA-ZHER2:S1 (7 ± 2) than the DOTA and NOTA conjugates (5.5 ± 0.6 vs.3.3 ± 0.6). The influence of chelator on the biodistribution and targeting properties was less pronounced for (68)Ga than for (111)In. The results of this study demonstrate that

  9. /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.

  10. 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

  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. Anti-3-[18F]FACBC Positron Emission Tomography-Computerized Tomography and 111In-Capromab Pendetide Single Photon Emission Computerized Tomography-Computerized Tomography for Recurrent Prostate Carcinoma: Results of a Prospective Clinical Trial

    PubMed Central

    Schuster, David M.; Nieh, Peter T.; Jani, Ashesh B.; Amzat, Rianot; Bowman, F. DuBois; Halkar, Raghuveer K.; Master, Viraj A.; Nye, Jonathon A.; Odewole, Oluwaseun A.; Osunkoya, Adeboye O.; Savir-Baruch, Bital; Alaei-Taleghani, Pooneh; Goodman, Mark M.

    2014-01-01

    Purpose We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[18F]FACBC compared to ProstaScint® (111In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. Materials and Methods A total of 93 patients met study inclusion criteria who underwent anti-3-[18F]FACBC positron emission tomography-computerized tomography plus 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. Results In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[18F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to 111In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[18F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to 111In-capromabpendetide with10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[18F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[18F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. Conclusions Better diagnostic performance was noted for anti-3-[18F]FACBC positron emission tomography-computerized tomography than for 111In

  13. Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106–115

    PubMed Central

    2016-01-01

    The ability of the cellular prion protein (PrPC) to bind copper in vivo points to a physiological role for PrPC in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrPC. Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting CuI and CuII binding properties. We have evaluated CuI coordination to the PrP(106–115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. CuI coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5–8, both methionine (Met) residues bind to CuI, forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrPC (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrPC to maintain the bound CuI ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant CuI-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrPC. This study provides further insight into the CuI coordination properties of His111 in human PrPC and the molecular mechanism of oxygen activation by this site. PMID:26930130

  14. Spectroscopic and Theoretical Study of Cu(I) Binding to His111 in the Human Prion Protein Fragment 106-115.

    PubMed

    Arcos-López, Trinidad; Qayyum, Munzarin; Rivillas-Acevedo, Lina; Miotto, Marco C; Grande-Aztatzi, Rafael; Fernández, Claudio O; Hedman, Britt; Hodgson, Keith O; Vela, Alberto; Solomon, Edward I; Quintanar, Liliana

    2016-03-21

    The ability of the cellular prion protein (PrP(C)) to bind copper in vivo points to a physiological role for PrP(C) in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrP(C). Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting Cu(I) and Cu(II) binding properties. We have evaluated Cu(I) coordination to the PrP(106-115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. Cu(I) coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5-8, both methionine (Met) residues bind to Cu(I), forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrP(C) (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrP(C) to maintain the bound Cu(I) ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant Cu(I)-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrP(C). This study provides further insight into the Cu(I) coordination properties of His111 in human PrP(C) and the molecular mechanism of oxygen activation by this site.

  15. 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

    PubMed Central

    Deppen, Stephen A.; Blume, Jeffrey; Bobbey, Adam J.; Shah, Chirayu; Graham, Michael M.; Lee, Patricia; Delbeke, Dominique; Walker, Ronald C.

    2017-01-01

    Neuroendocrine tumors (NETs) are uncommon tumors with increasing incidence and prevalence. Current reports suggest that 68Ga-DOTATATE PET/CT imaging improves diagnosis and staging of NETs compared with 111In-DTPA-octreotide and conventional imaging. We performed a systematic review of 68Ga-DOTATATE for safety and efficacy compared with octreotide and conventional imaging to determine whether available evidence supports U.S. Food and Drug Administration approval. Methods Medline, EMBASE, Web of Science, and Cochrane Reviews electronic databases were searched from January 1999 to September 2015. Results were restricted to human studies comparing diagnostic accuracy of 68Ga-DOTATATE with octreotide or conventional imaging for pulmonary or gastroenteropancreatic NET and for human studies reporting safety/ toxicity for 68Ga-DOTATATE with 10 subjects or more thought to have NETs. Direct communication with corresponding authors was attempted to obtain missing information. Abstracts meeting eligibility criteria were collected by a research librarian and assembled for reviewers; 2 reviewers independently determined whether or not to include each abstract. If either reviewer chose inclusion, the abstract was accepted for review. Results Database and bibliography searches yielded 2,479 articles, of which 42 were eligible. Three studies compared the 2 radiopharmaceuticals in the same patient, finding 68Ga-DOTATATE to be more sensitive than octreotide. Nine studies compared 68Ga-DOTATATE with conventional imaging. 68Ga-DOTATATE estimated sensitivity, 90.9% (95% confidence interval, 81.4%–96.4%), and specificity, 90.6% (95% confidence interval, 77.8%–96.1%), were high. Five studies were retained for safety reporting only. Report of harm possibly related to 68Ga-DOTATATE was rare (6 of 974), and no study reported major toxicity or safety issues. Conclusion No direct comparison of octreotide and 68Ga-DOTATATE imaging for diagnosis and staging in an unbiased population of NETs

  16. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy

    SciTech Connect

    Gokhale, Abhay S.; Mayadev, Jyoti; Pohlman, Brad . E-mail: macklir@ccf.org

    2005-09-01

    Purpose: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. Methods and Materials: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. Results: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of 'bulky' (maximal diameter {>=}5 cm) disease displayed evidence of progression vs. 28% (26/93) of 'nonbulky' disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. Conclusion: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

  17. In situ STM investigation of the lithium underpotential deposition on Au(111) in the air- and water-stable ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide.

    PubMed

    Gasparotto, L H S; Borisenko, N; Bocchi, N; El Abedin, S Zein; Endres, F

    2009-12-21

    In the present paper the underpotential deposition (UPD) of lithium on Au(111) from 0.5 mol L(-1) LiTFSA in the air- and water stable ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide, [Py(1,4)]TFSA, has been investigated by cyclic voltammetry (CV) and in situ scanning tunneling microscopy (STM). The pure [Py(1,4)]TFSA was found to be inert in the potential regime investigated. The results show that the lithium UPD on Au(111) in [Py(1,4)]TFSA begins at potentials considerably positive to the electrode potential of bulk deposition and follows a layer-by-layer mechanism with the formation of at least two monolayers. A large number of monoatomically deep pits appear when the potential reaches positive values, which is an indication that a Li-Au alloy was formed.

  18. Targeted cancer therapy with a novel low-dose rate alpha-emitting radioimmunoconjugate.

    PubMed

    Dahle, Jostein; Borrebaek, Jørgen; Jonasdottir, Thora J; Hjelmerud, Anne Kristine; Melhus, Katrine B; Bruland, Øyvind S; Press, Oliver W; Larsen, Roy H

    2007-09-15

    Alpha-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, alpha-emitting antibody conjugates have been difficult to exploit clinically due to the short half-life of the radionuclides, low production capability, or limited source materials. We have developed a novel technology based on the low-dose rate alpha-particle-emitting nuclide (227)Th, exemplified here using the monoclonal antibody rituximab. In vitro, this radioimmunoconjugate killed lymphoma cells at Becquerel per milliliter (Bq/mL) levels. A single injection of (227)Th-rituximab induced complete tumor regression in up to 60% of nude mice bearing macroscopic (32-256 mm(3)) human B-lymphoma xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy with (227)Th-rituximab was significantly more effective than the control radioimmunoconjugate (227)Th-trastuzumab and the standard beta-emitting radioimmunoconjugate for CD20(+) lymphoma(90)Y-tiuxetan-ibritumomab. Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers.

  19. Zevalin and BEAM (Z-BEAM) versus rituximab and BEAM (R-BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma.

    PubMed

    Berger, Martin D; Branger, Giacomo; Klaeser, Bernd; Taleghani, Behrouz Mansouri; Novak, Urban; Banz, Yara; Mueller, Beatrice U; Pabst, Thomas

    2016-09-01

    Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high-dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty-five patients had rituximab and BEAM (R-BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium-90 labeled CD20 targeting antibody, prior to BEAM (Z-BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5-year overall survival (OS) in the R-BEAM and Z-BEAM groups was 55% and 71% (p = 0.288), and the 4-year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z-BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R-BEAM. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Radioimmunotherapy in a radiation oncology environment: Building a multi-specialty team

    SciTech Connect

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

    2006-10-01

    Radioimmunotherapy (RIT) is a new branch of radiation medicine in which antibodies specific for tumor-associated antigens are linked to radioactive atoms to provide biologically targeted short-range molecular radiotherapy. Two such biologically targeted radiopharmaceuticals have been approved for commercial use in the last few years. Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) both recognize the CD-20 surface antigen found on normal and malignant B cells. Both of these compounds produce impressive clinical results when used in the management of indolent, refractory, and transformed CD-20+ B-cell non-Hodgkin's lymphoma, but the unsealed sources involved in this class of compounds also require new types of patient care coordination and patient/environmental safety procedures. Because these multifunctional compounds are ideally administered through a multi-departmental team approach, the planning process to initiate and direct such a team is quite important. This article reviews some of the key processes that may be necessary to establish a successful clinical RIT team. The manuscript highlights the important roles that Radiation oncology team members may play in this multi-department enterprise.

  1. Clinical development of radioimmunotherapy for B-cell non-Hodgkin's lymphoma

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu; Knox, Susan J.

    2006-10-01

    Over the past several decades, several biomolecules have been investigated for their ability to deliver radiation to cancer cells, but antibodies have been the carriers of choice in systemic targeted radionuclide therapy (STaRT). Two radioimmunotherapy agents that target the CD20 antigen, {sup 131}I-tositumomab and {sup 9}Y-ibritumomab tiuxetan, have been approved by the U.S. Food and Drug Administration for the treatment of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL), and clinical trials have shown that they are effective as monotherapies in the salvage setting, producing response rates that are often higher and durations of response that are often longer than those with chemotherapy. Escalated doses of these agents can be supported with stem cell transplantation and can produce high rates of complete response and greater survival in patients with relapsed NHL. The quality and duration of responses are greater with radioimmunotherapy when it is used earlier in the course of treatment.

  2. Utility of 11C-methionine and 11C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model: comparison to autologous 111In-labelled leukocytes, 99mTc-DPD, and 18F-FDG

    PubMed Central

    Afzelius, Pia; Alstrup, Aage KO; Schønheyder, Henrik C; Borghammer, Per; Jensen, Svend B; Bender, Dirk; Nielsen, Ole L

    2016-01-01

    The aim of this study was to compare 11C-methionine and 11C-donepezil positron emission tomography (PET) with 111In-labeled leukocyte and 99mTc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and 18F-fluorodeoxyglucose (18F-FDG) PET to improve detection of osteomyelitis. The tracers’ diagnostic utility where tested in a juvenile porcine hematogenously induced osteomyelitis model comparable to osteomyelitis in children. Five 8-9 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, 11C-methionine and 11C-donepezil PET, 99mTc-DPD and 111In-labelled leukocytes scintigraphy, and 18F-FDG PET. This was followed by necropsy of the pigs and gross pathology, histopathology, and microbial examination. The pigs developed a total of 24 osteomyelitic lesions, 4 lesions characterized as contiguous abscesses and pulmonary abscesses (in two pigs). By comparing the 24 osteomyelitic lesions, 18F-FDG accumulated in 100%, 111In-leukocytes in 79%, 11C-methionine in 79%, 11C-donepezil in 58%, and 99mTc-DPD in none. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT and 11C-methionine in marking infectious lesions. PMID:28078182

  3. Utility of (11)C-methionine and (11)C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model: comparison to autologous (111)In-labelled leukocytes, (99m) Tc-DPD, and (18)F-FDG.

    PubMed

    Afzelius, Pia; Alstrup, Aage Ko; Schønheyder, Henrik C; Borghammer, Per; Jensen, Svend B; Bender, Dirk; Nielsen, Ole L

    2016-01-01

    The aim of this study was to compare (11)C-methionine and (11)C-donepezil positron emission tomography (PET) with (111)In-labeled leukocyte and (99m) Tc-DPD (Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid) single-photon emission computed tomography (SPECT), and (18)F-fluorodeoxyglucose ((18)F-FDG) PET to improve detection of osteomyelitis. The tracers' diagnostic utility where tested in a juvenile porcine hematogenously induced osteomyelitis model comparable to osteomyelitis in children. Five 8-9 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus. The sequential scan protocol included Computed Tomography, (11)C-methionine and (11)C-donepezil PET, (99m) Tc-DPD and (111)In-labelled leukocytes scintigraphy, and (18)F-FDG PET. This was followed by necropsy of the pigs and gross pathology, histopathology, and microbial examination. The pigs developed a total of 24 osteomyelitic lesions, 4 lesions characterized as contiguous abscesses and pulmonary abscesses (in two pigs). By comparing the 24 osteomyelitic lesions, (18)F-FDG accumulated in 100%, (111)In-leukocytes in 79%, (11)C-methionine in 79%, (11)C-donepezil in 58%, and (99m) Tc-DPD in none. Overall, (18)F-FDG PET was superior to (111)In-leukocyte SPECT and (11)C-methionine in marking infectious lesions.

  4. Double layer effects in electrocatalysis: the oxygen reduction reaction and ethanol oxidation reaction on Au(111), Pt(111) and Ir(111) in alkaline media containing Na and Li cations.

    SciTech Connect

    Lopes, Pietro P.; Strmcnik, Dusan; Jirkovsky, Jakub S.; Connell, Justin G.; Stamenkovic, Vojislav; Markovic, Nenad

    2016-03-15

    Oxygen reduction and ethanol oxidation reactions were studied on Au(111), Pt(111) and Ir(111) in alkaline solutions containing sodium and/or lithium cations. By keeping the same (111) surface orientation and exploring oxophilicity trends and non-covalent interactions between OHad and alkali metal cations (AMCn+), we were able to gain deep insights into the multiple roles that OHad plays in these important electrocatalytic reactions. Cyclic voltammetry experiments revealed that OHad formation initiates at distinct electrode potentials, governed by the oxophilicity of the specific metal surface, with further OHad adlayer stabilization by non-covalent alkali-cation interactions and affecting the formation of a “true oxide” layer at higher electrode potentials. Although OHad is a simple spectator for the ORR, it promotes the ethanol oxidation reaction (EOR) at lower potentials and act as spectator at high OHad coverages. By changing the alkali metal cation at the interface (Li+) on more oxophilic surfaces, it was possible to promote the EOR even more, relative to Na+, without changing the product distribution for the reaction. This cation effect suggests that OHad---Li+(H2O)x clusters can stabilize the ethoxide adlayer, thus improving the EOR activity. Our results indicate the importance of the entire electrochemical interface in determining the electrocatalytic activity during reaction.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. [Cancer therapy using unsealed radioisotopes-the present and future].

    PubMed

    Karasawa, Katsuyuki

    2014-12-01

    Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants and cancer cells in well-differentiated thyroid cancers. It has also been used for metastatic well-differentiated thyroid cancers, especially lung and bone metastases. For small lung metastases, I-131 treatment has curative potential, particularly in young patients. Suppression of the thyroid stimulating hormone is also important for prolonging the survival of thyroid cancer patients. Strontium-89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for the treatment of bone metastases, especially osteoblastic metastases. It has been reported to have analgesic effects in an average of 76% of cases, and it is more effective if used in the early bone metastatic phase. Ibritumomab tiuxetan (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y-90). It is used for treatment-resistant low grade or follicular B-cell non-Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been used for bone metastases from castration resistant prostate cancers, and in a phase III trial, it has been proven to prolong survival of these patients. Cancer therapy using unsealed radioisotopes has been thought to be promising because it exhibits more targeted therapy than external beam irradiation. Therefore, if many more ideal targeting agents are developed in the future, this treatment might be used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available for treating bone metastasis, the combined use of other treatments such as high precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted agents should be investigated.

  10. 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.

  11. An 111In-Pentetreotide Positive Sclerosing Pneumocytoma.

    PubMed

    Savelli, Giordano; Bnà, Claudio; Zambelli, Claudia; Illuminati, Sonia; Bonello, Luke

    2017-04-01

    A 43-year-old woman had an incidental lung mass identified on shoulder x-ray performed for pain. Contrast-enhanced CT showed a 38-mm mass in the medial segment of the right middle lobe, with features suggestive of carcinoid tumor. A In-pentetreotide scan showed intense uptake; furthermore, fine needle aspiration biopsy yielded neuroendocrine cells confirming the carcinoid hypothesis. However, definitive surgical histology showed a sclerosing pneumocytoma. This could potentially suggest that such rare tumors, with metastatic potential, could respond to somatostatin analogue treatment.

  12. Equivalent dose rate at 1m of patients with known or suspected neuroendocrine tumor exiting a nuclear medicine department after (68)Ga-DOTATOC, (18)F-FDOPA or (18)F-FDG PET/CT, or (111)In-pentetreotide or (123)I-mIBG SPECT/CT.

    PubMed

    Zhang-Yin, Jules; Dirand, Anne-Sophie; Sasanelli, Myriam; Corrégé, Gwenaelle; Peudon, Aude; Kiffel, Thierry; Nataf, Valérie; Clerc, Jérôme; Montravers, Françoise; Talbot, Jean-Noël

    2017-02-16

    (123)I-mIBG and (111)In-pentetrotide SPECT have been used for functional imaging of neuroendocrine tumors (NET) for the last two decades. More recently, PET/CT imaging with (18)F-FDG, (18)F-FDOPA and (68)Ga somatostatin-receptor ligands in NETs has been expanding. No direct measurements of the dose rate from NET patients exiting the nuclear medicine department could be found in the literature after PET/CT with (18)F-FDOPA or (68)Ga-DOTATOC, a somatostatin analogue. Methods: We measured the dose rates from NET patients undergoing PET/CT or SPECT/CT in our centers. A total of 103 paired measurements of equivalent dose rate at 1m of the patient (EDR-1m) were performed in 98 patients on leaving the department. The detector was facing the sternum or the urinary bladder, at a distance of 1 meter from and right in front of the patient. The practice for exiting the department differed according to whether the patient was referred to PET/CT or to SPECT/CT. PET/CT patients were discharged after imaging. Results: The median administered activity was 122 MBq in 53 (68)Ga-DOTATOC PET/CTs, 198 MBq in 15 (18)F-FDOPA PET/CTs and 176 MBq in 13 (18)F-FDG PET/CTs. The corresponding median EDR-1m (in µSv/h) were 4.8, 9.5 and 8.8 respectively facing the sternum, and 5.1, 10.1 and 9.5 respectively facing the bladder. SPECT/CT patients left the department earlier, just after radiopharmaceutical injection. The median administered activity was 170 MBq in 12 (111)In-pentetreotide SPECT/CTs and 186 MBq in 10 (123)I-mIBG SPECT/CTs. The corresponding median EDR-1m (in µSv/h) were 9.4, and 4.9 respectively at the level of the sternum, and 9.3 and 4.7 respectively at the level of the bladder. The EDR-1m was <20 µSv/h in all patients. Thus when exiting the nuclear medicine department, the NET patients injected with (68)Ga-DOTATOC or (123)I mIBG emitted an average EDR-1m roughly half of that of patients injected with other radiopharmaceuticals. This is a complementary argument for replacing

  13. A Monte Carlo and physical phantom evaluation of quantitative In-111 SPECT

    NASA Astrophysics Data System (ADS)

    He, Bin; Du, Yong; Song, Xiyun; Segars, W. Paul; Frey, Eric C.

    2005-09-01

    Accurate estimation of the 3D in vivo activity distribution is important for dose estimation in targeted radionuclide therapy (TRT). Although SPECT can potentially provide such estimates, SPECT without compensation for image degrading factors is not quantitatively accurate. In this work, we evaluated quantitative SPECT (QSPECT) reconstruction methods that include compensation for various physical effects. Experimental projection data were obtained using a GE VH/Hawkeye system and an RSD torso phantom. Known activities of In-111 chloride were placed in the lungs, liver, heart, background and two spherical compartments with inner diameters of 22 mm and 34 mm. The 3D NCAT phantom with organ activities based on clinically derived In-111 ibritumomab tiuxetan data was used for the Monte Carlo (MC) simulation studies. Low-noise projection data were simulated using previously validated MC simulation methods. Fifty sets of noisy projections with realistic count levels were generated. Reconstructions were performed using the OS-EM algorithm with various combinations of attenuation (A), scatter (S), geometric response (G), collimator-detector response (D) and partial volume compensation (PVC). The QSPECT images from the various combinations of compensations were evaluated in terms of the accuracy and precision of the estimates of the total activity in each organ. For experimental data, the errors in organ activities for ADS and PVC compensation were less than 6.5% except the smaller sphere (-11.9%). For the noisy simulated data, the errors in organ activity for ADS compensation were less than 5.5% except the lungs (20.9%) and blood vessels (15.2%). Errors for other combinations of compensations were significantly (A, AS) or somewhat (AGS) larger. With added PVC, the error in the organ activities improved slightly except for the lungs (11.5%) and blood vessels (3.6%) where the improvement was more substantial. The standard deviation/mean ratios were all less than 1.5%. We

  14. 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.

  15. Cadmium underpotential deposition on Cu(111) in situ scanning tunneling microscopy.

    PubMed

    Hommrich, J; Hümann, S; Wandelt, K

    2002-01-01

    Atomically resolved in situ STM images are presented for an underpotentially deposited (upd) cadmium layer on a Cu(111) electrode from a 10(-4) M CdCl2/10(-2) M HCl solution. The observed moiré-like structure seen in the images is analysed by means of an algebraic model for this long-range superstructure. A structure model for the upd layer is developed which reflects all features of the observed moiré pattern. Furthermore the height modulation was simulated by a hard-sphere model for the Cd overlayer and shows remarkable agreement with the detailed tunneling current density distribution of the measured STM images. The existence of translational and rotational domains is demonstrated. The results are also compared and shown to be fully consistent with previous (ex situ) low-energy electron diffraction (LEED) observations of this system. The mechanism of Cd upd involves a dynamic site exchange between preadsorbed Cl- anions and adsorbing Cd2+ cations as previously concluded from ex situ X-ray photoelectron (XPS) and low-energy ion scattering (LEIS) measurements.

  16. 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.

  17. 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.

  18. Clearance patterns for {sup 111}In-oxide particles deposited in specific airways of beagle dogs

    SciTech Connect

    Snipes, M.B.; Muggenburg, B.A.; Griffith, W.C.; Guilmette, R.A.

    1994-11-01

    The International Commission on Radiological Protection (ICRP) has incorporated long-term retention of radioactive particles in conducting airways into its newly approved respiratory tract dosimetry model. This model is purported to provide a better basis for assessing risk associated with human inhalation exposures to radioactive particles. However, applying the new model requires an understanding of particle retention patterns in conducting airways of the lung. Studies are being conducted at ITRI to quantify long-term retention patterns for particles deposited at specific sites in conducting airways of Beagle dogs. The dog was selected as a model because long-term retention and clearance patterns for particles deposited in the lungs of dogs and humans are similar.

  19. Corrective 111 In Capromab Pendetide SPECT Image Reconstruction Methods for Improved Detection of Recurrent Prostate Cancer

    DTIC Science & Technology

    2006-06-01

    with compensation for attenuation and detector response (OSAD). The results in pink are from 25% lesion contrast with respect to background and the...Trans. Nucl. Sci., 1980. NS-27(3): p. 1137-1153. 10. Jaszczak, R.J., C.E. Floyd , Jr., and R.E. Coleman, Scatter Compensation Techniques For SPECT

  20. The Comparison of Wading Measurement Discharge between ADC and FP111 in Shallow Flow

    NASA Astrophysics Data System (ADS)

    Yang, H. C.; Chiang, C. J.

    2012-04-01

    During the low water period, the water depth of streams in Taiwan is very shallow and the velocity is too slow; the discharge in the streams is relatively small. At this time, larger velocity measurement equipments such as Price Type AA cannot be completely submerged in water so that they are unable to be applied to measure the velocity. Discharge measurements using conventional methods, including Price Type AA suspended in the water from bridge, are therefore unusable. The discharge records during the low water period can provide required information for monitoring ecological reference flow and various related applications of water intake engineering design. Therefore, it is necessary to choose an appropriate equipment to measure the discharge in shallow water flow in order to continuously carry out the monitoring and recording the discharge. This study is conducted in Linbian river basin, selecting Laiyi Bridge in Linbian Township Pingtung County as the gauging station. The research uses Acoustic Digital Current Meter (ADC) and Digital water velocity meter (FP111 Global Flow Probe) to measure the discharge of river during the low water period in order to explore the applicability and deviation of the two equipments which have different features and measurement principles. There are 11 discharges conducted in this study. The method of calculating the discharge is to get the sum of the measured discharge of sub-section in each measurement. Furthermore, based on velocity-area principle in Mean-Section Method, the total discharge can be estimated from the velocity data obtained by using velocity equipment. The result of the study indicates that both equipments can be applied to measure the discharge on the condition that the measurement probe should be completely submerged in water. However, ADC is more applicable than FP111 to measure discharge in shallow water flow because the precision of ADC is 7.96% higher than that of FP111. Also, through the independent sample T-test in statistical analysis, the result of difference of means test analysis shows that there is no significant difference in the measured data using the two different equipments. Due to its higher precision, ADC is relatively capable to obtain the flow velocity in small flow. When the velocity is very small (i.e., flow velocity is 0.01 m/s), ADC is still able to measure the velocity, but its price is relatively more expensive. If the precision of measured data is taken into account, it is recommended to use ADC to measure the discharge. If the expensive equipment is unattainable because of funding issue, FP111 can be used to conduct the measurement in order to obtain the required flow field of the study area. Keywords: Acoustic Digital Current Meter; Measurement Discharge; Mean-Section Method; Shallow Flow.

  1. 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.

  2. 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.

  3. Underpotential deposition of Cu on Au(111) in sulfate-containing electrolytes: A theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Sung, Yung-Eun; Rikvold, Per Arne; Wieckowski, Andrzej

    1996-04-01

    We study the underpotential deposition of Cu on single-crystal Au(111) electrodes in sulfate-containing electrolytes by a combination of computational statistical-mechanics based lattice-gas modeling and experiments. The experimental methods are in situ cyclic voltammetry and coulometry and ex situ Auger electron spectroscopy and low-energy electron diffraction. The experimentally obtained voltammetric current and charge densities and adsorbate coverages are compared with the predictions of a two-component lattice-gas model for the coadsorption of Cu and sulfate. This model includes effective, lateral interactions out to fourth-nearest neighbors. Using group-theoretical ground-state calculations and Monte Carlo simulations, we estimate effective electrovalences and lateral adsorbate-adsorbate interactions so as to obtain overall agreement with experiments, including both our own and those of other groups. In agreement with earlier work, we find a mixed (√3×√3) phase consisting of 2/3 monolayer Cu and 1/3 monolayer sulfate at intermediate electrode potentials, delimited by phase transitions at both higher and lower potentials. Our approach provides estimates of the effective electrovalences and lateral interaction energies, which cannot yet be calculated by first-principles methods.

  4. Cluster variation study of the underpotential deposition of Cu on Au(111) in the presence of bisulfate

    NASA Astrophysics Data System (ADS)

    Huckaby, Dale A.; Legault, Marc D.; Blum, L.

    1998-09-01

    A cluster variation method is developed to study the phase transitions and the structures of phases which occur at the fluid-crystal interface during the underpotential deposition of a metal on an electrode in the presence of an anion, such as bisulfate. In addition to the possibility of first-order condensation phase transitions occurring during the deposition of a metal, the steric repulsion of adsorbed anions can also cause an order-disorder transition. Using clusters containing six adsorption sites, the method is applied to the underpotential deposition of copper on (111) gold in the presence of bisulfate. In order to fix a constant in the expression for the entropy, the effect of the hard-core exclusion of a pair of first-neighbor bisulfates, in addition to the effect of finite interactions, is calculated exactly in the limit of high temperature. The cluster method yields two coupled adsorption isotherms for copper and bisulfate in terms of their activities and coverages. The resulting isotherms show an order-disorder transition due to the hard-core exclusion of neighboring bisulfate ions, as well as two first-order phase transitions in the copper and bisulfate coverages which correspond to the two spikes in the experimental voltammogram. The cluster method also gives the local structure of the phases which occur as the voltage is changed.

  5. 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.

  6. Quantitative evaluation of indium-111 (In-111) octreotide pituitary activity: Comparison in patient with and without pituitary tumors

    SciTech Connect

    Gupta, P.; Waxman, A.; Nguyen, K.

    1995-05-01

    Indium 111 Octreotide is known to detect pituitary tumors. Variable low level pituitary activity has been reported in pts. with no demonstrable pituitary tumors. To our knowledge, there have been no studies which quantitatively categorize pituitary activity with respect to distinguishing normal subject from pts. with pituitary tumors. 13 pts. with proven, treated acromegaly were included, as well as 15 pts. with no history of pituitary disorder. Both groups underwent SPECT In-111 scintigraphy 24 hours post-injection Average count per pixel ratios were obtained for the pituitary/calvarium (P/C) and pituitary/brain (P/B) regions. 10 pts. with acromegaly underwent growth hormone (GH) measurements 2 hours post-glucose load. Statistical correlation between growth hormone levels using P/C and P/B ratios were obtained. P/C ratios, as well as P/B ratios demonstrated high correlation with serum GH levels correlation coefficient(r)= .717 for P/C p<0.05, and correlation coefficient(r) = 0.828 for P/B ratios p<0.005. P/C ratios and P/B ratios for controls correlated closely with the upper level of normal predicted by P/C or P/B ratios as a function of serum growth hormone found in patients with acromegaly. Somatostatin receptor SPECT scintigraphy of the pituitary and appropriate quantitation can predict patients with growth hormone secreting tumors.

  7. Characterizing and quantilying controls on arsenic solubility over a pH range of 1-11 in a uranium mill-scale experiment.

    PubMed

    Moldovan, Brett I; Hendry, M Jim

    2005-07-01

    A mill-scale hydrometallurgical experiment (2700 m3 of effluent treated/day) was conducted for three months at the Rabbit Lake uranium mine site located in northern Saskatchewan, Canada, to determine the controls on the solubility of dissolved arsenic over a pH range of 1-11 and to develop a thermodynamic database for the dominant mineralogical controls on arsenic in the mill and the resulting mill tailings. The arsenic concentrations in the mill ranged from 526 mg/L at pH 1.0 (initial) to 1.34 mg/L at pH 10.8 (final discharge). Geochemical modeling of the chemistry data shows that arsenic solubility is controlled by the formation of scorodite (FeAsO4-2H2O) from pH 2.4 to pH 3.1, with 99.8% of dissolved arsenic precipitated as scorodite. Model results show that scorodite is unstable (releasing arsenic back in to solution) above pH 3.1 and arsenic adsorption to the surface of 2-line ferrihydrite is the dominant controlling factor in the solubility of arsenic from pH 3.2 to pH 11.0, with 99.8% of dissolved arsenic removed from solution via this mechanism. Finally, model results show -0.2% of the total dissolved arsenic adsorbs to the surface of amorphous aluminum hydroxide from pH 5.0 to pH 8.0. Minor alterations to the thermodynamic properties of arsenite and arsenate adsorption to 2-line ferrihydrite allowed the fit between measured mill-scale and modeled concentrations for the pH range of 3.2-11.0 to be optimized.

  8. [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.

  9. Quantitative in Situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-in-Pentetreotide. Addendum

    DTIC Science & Technology

    2008-05-01

    such as autoradiography and RT-PCR in vitro and scintigraphy in vivo. We have developed a series of algorithms called AQUA that can assess protein...defines microvessel area as a prognostic parameter in clear cell renal cell cancer. Hum Pathol 2007;38:1454-1462. 39. Berger AJ, Kluger HM, Li N

  10. 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.

  11. Electron stimulated oxidation of Al(111) in H2O vapor: Dipole orientation effects in the Al2O3 thin film

    NASA Astrophysics Data System (ADS)

    Popova, I.; Zhukov, V.; Yates, J. T.; Chen, J. G.

    1999-12-01

    The electron stimulated oxidation of Al(111) using H2O(g) as a source of oxygen has been investigated at 300 K using near edge x-ray absorption fine structure (NEXAFS) and Auger electron spectroscopy. Irradiation with electrons (100 eV, 50 μA/cm2) produced thick Al2O3 film layers (up to 15 Å), compared to the films grown thermally (4 Å) by the same water exposure. A preferential normal orientation of the O-Al bonds was found for the films grown by the electron assisted process, causing the O K-edge NEXAFS spectra to depend on the incident angle of the polarized x-ray beam. In contrast, little polarization of the O-Al bonds was found for the case of Al2O3 films grown by thermal oxidation in H2O(g).

  12. Strain in epitaxial MnSi films on Si(111) in the thick film limit studied by polarization-dependent extended x-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Figueroa, A. I.; Zhang, S. L.; Baker, A. A.; Chalasani, R.; Kohn, A.; Speller, S. C.; Gianolio, D.; Pfleiderer, C.; van der Laan, G.; Hesjedal, T.

    2016-11-01

    We report a study of the strain state of epitaxial MnSi films on Si(111) substrates in the thick film limit (100-500 Å) as a function of film thickness using polarization-dependent extended x-ray absorption fine structure (EXAFS). All films investigated are phase-pure and of high quality with a sharp interface between MnSi and Si. The investigated MnSi films are in a thickness regime where the magnetic transition temperature Tc assumes a thickness-independent enhanced value of ≥43 K as compared with that of bulk MnSi, where Tc≈29 K . A detailed refinement of the EXAFS data reveals that the Mn positions are unchanged, whereas the Si positions vary along the out-of-plane [111] direction, alternating in orientation from unit cell to unit cell. Thus, for thick MnSi films, the unit cell volume is essentially that of bulk MnSi—except in the vicinity of the interface with the Si substrate (thin film limit). In view of the enhanced magnetic transition temperature we conclude that the mere presence of the interface, and its specific characteristics, strongly affects the magnetic properties of the entire MnSi film, even far from the interface. Our analysis provides invaluable information about the local strain at the MnSi/Si(111) interface. The presented methodology of polarization dependent EXAFS can also be employed to investigate the local structure of other interesting interfaces.

  13. Ordered molecular assemblies of substituted bis(phthalocyaninato) rare earth complexes on Au(111): in situ scanning tunneling microscopy and electrochemical studies.

    PubMed

    Ma, Houyi; Yang, Liang-Yueh Ou; Pan, Na; Yau, Shueh-Lin; Jiang, Jianzhuang; Itaya, Kingo

    2006-02-28

    Substituted bis(phthalocyaninato) rare earth complexes ML2 (M = Y and Ce; L = [Pc(OC8H17)8]2, where Pc = phthalocyaninato) were adsorbed onto single crystalline Au(111) electrodes from benzene saturated with either YL2 or CeL2 complex at room temperature. In situ scanning tunneling microscopy (STM) and cyclic voltammetry (CV) were used to examine the structures and the redox reactions of these admolecules on Au(111) electrodes in 0.1 mol dm(-3) HClO4. The CVs obtained with YL2- and CeL2-coated Au(111) electrodes respectively contained two and three pairs of redox peaks between 0 and 1.0 V (versus reversible hydrogen electrode). STM molecular resolution revealed that YL2 and CeL2 admolecules were imaged as spherical protrusions separated by 2.3 nm, which suggests that they were oriented with their molecular planes parallel to the unreconstructed Au(111)-(1 x 1). Both molecules when adsorbing from approximately micromolar benzene dosing solutions produced mainly ordered arrays characterized as (8 x 5 radical3)rect (theta = 0.0125). The redox reactions occurring between 0.2 and 1.0 V caused no change in the adlayer, but they were desorbed or oxidized at the negative and positive potential limits. The processes of adsorption and desorption at the negative potentials were reversible to the modulation of potential. Electrochemical impedance spectroscopy (EIS) and CV measurements showed that YL2 and CeL2 adlayers could block the adsorption of perchlorate anions and mediating electron transfer at the Au(111) electrode, leading to the enhancement of charge transfer for the ferro/ferricyanide redox couple.

  14. NMR study suggests a major role for Arg111 in maintaining the structure and dynamical properties of type II human cellular retinoic acid binding protein.

    PubMed

    Wang, L; Yan, H

    1998-09-15

    The solution structure of a site-directed mutant of type-II human cellular retinoic acid binding protein (CRABPII) with Arg111 replaced by methionine (R111M) has been determined by NMR spectroscopy. The sequential assignments of the 1H and 15N resonances of apo-R111M were established by multinuclear multidimensional NMR. The solution structure was calculated from 2302 distance restraints and 77 phi dihedral restraints derived from the NMR data. The root-mean-square deviation of the ensemble of 28 refined conformers that represent the structure from the mean coordinate set derived from them was 0.54 +/- 0.26 and 0.98 +/- 0.23 A for the backbone atoms and all heavy atoms, respectively. The solution structure of apo-R111M is similar to that of wild-type apo-CRABPII. However, there are significant conformational differences between the two proteins, localized mainly to three segments (Leu19-Ala36, Glu73-Cys81, and Leu99-Pro105) clustered around the ligand entrance more than 17 A away from the point mutation. In apo-R111M, all the three segments move toward the center of the ligand entrance so that the opening of the ligand-binding pocket in apo-R111M is much smaller than that in wild-type apo-CRABPII. Furthermore, the ligand-binding pocket of apo-R111M, especially the ligand entrance, is much less flexible than that of apo-CRABPII. Surprisingly, apo-R111M is more similar to holo-CRABPII than to apo-CRABPII in both structure and dynamical properties. The conformational and dynamical changes caused by the mutation are similar to those induced by binding of RA, although the magnitudes of the changes caused by the mutation are smaller than those induced by binding of RA. The results suggest that Arg111 plays a critical role in determining the structure and dynamical properties of CRABPII.

  15. Significance of bone-marrow scintigraphy in aplastic anemia: concise communication. [/sup 99m/Tc-sulfur colloid; /sup 111/In-transferrin

    SciTech Connect

    Najean, Y.; Le Danvic, M.; Le Mercier, N.; Pecking, A.; Colonna, P.; Rain, J.D.

    1980-03-01

    Tc-99m colloid and In-111 transferrin were used in a semiquantitative scintigraphic study of bone-marrow activity in 76 patients with aplastic anemia, the majority of which were severe cases. The results are compared with other known prognostic parameters and with a predictive index formulated from a prior multiparametric analysis performed in 352 cases. In 47 cases parallel abnormality of Tc and In uptakes was noted and was well correlated with other prognostic factors. Indium uptake is apparently a good indicator of the severity of aplasia; extension of active erythroid tissue, demonstrated with this method, is correlated with prognosis. In nine cases, excessive in uptake is explained by dyserythropoiesis associated with granulo- and thrombocytopenia (Fanconi's anemia in most cases). In 20 of our patients, TcSC uptake was excessive compared with that of In and with other prognostic factors. Statistically, this phenomenon carries an unfavorable prognosis but its physiological meaning remains to be defined.

  16. 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.

  17. 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.

  18. Quantitative in Situ Assessment of the Somatostatin Receptor in Breast Cancer to Assess Response to Targeted Therapy with 111-In-Pentetreotide

    DTIC Science & Technology

    2005-05-01

    expression a s a whole was substantially diminished compared to our breast cancer cohor t (Figure 2) . 5 20 40 60 80 100 120 AQUA...concentratio n We have gathered a series of cultured cell lines from ATCC for this task . These include breast cancer lines (MB175UN, BT474 , SKBR3, MB468...SST) is a peptide hormone implicated in the growth and progression o f cancers and SSTR2 is the predominant receptor subtype expressed in

  19. Effectiveness of quenchers to reduce radiolysis of (111)In- or (177)Lu-labelled methionine-containing regulatory peptides. Maintaining radiochemical purity as measured by HPLC.

    PubMed

    de Blois, Erik; Chan, Ho Sze; Konijnenberg, Mark; de Zanger, Rory; Breeman, Wouter A P

    2012-01-01

    An overview how to measure and to quantify radiolysis by the addition of quenchers and to maintain Radio-Chemical Purity (RCP) of vulnerable methionine-containing regulatory peptides is presented. High RCP was only achieved with a combination of quenchers. However, quantification of RCP is not standardized, and therefore comparison of radiolabelling and RCP of regulatory peptides between different HPLC-systems and between laboratories is cumbersome. Therefore we suggest a set of standardized requirements to quantify RCP by HPLC for radiolabelled DTPA- or DOTA-peptides. Moreover, a dosimetry model was developed to calculate the doses in the reaction vials during radiolabelling and storage of the radiopeptides, and to predict RCP in the presence and absence of quenchers. RCP was measured by HPLC, and a relation between radiation dose and radiolysis of RCP was established. The here described quenchers are tested individually as ƒ(concentration) to investigate efficacy to reduce radiolysis of radiolabelled methionine-containing regulatory peptides.

  20. Development of the TFX F-111 in the Department of Defense’s Search for Multi-Mission, Joint-Service Aerial Platforms

    DTIC Science & Technology

    2011-06-10

    Release; Distribution is Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT In 1961, the new Secretary of Defense, Robert McNamara directed a joint...Hollister, M.A. Accepted this 10th day of June 2011 by: , Director, Graduate Degree Programs Robert F. Baumann, Ph.D. The opinions and...new Secretary of Defense, Robert McNamara directed a joint aircraft acquisition program called the TFX, which would produce the first common aerial

  1. Unraveling transition metal dissolution of Li1.04Ni1/3Co1/3Mn1/3O2 (NCM 111) in lithium ion full cells by using the total reflection X-ray fluorescence technique

    NASA Astrophysics Data System (ADS)

    Evertz, Marco; Horsthemke, Fabian; Kasnatscheew, Johannes; Börner, Markus; Winter, Martin; Nowak, Sascha

    2016-10-01

    In this work we investigated the transition metal dissolution of the layered cathode material Li1.04Ni1/3Co1/3Mn1/3O2 in dependence on the cycle number and cut-off cell voltage during charge by using the total reflection X-ray fluorescence technique for the elemental analysis of the specific lithium ion battery degradation products. We could show that with ongoing cycling transition metal dissolution from the cathode increased over time. However, it was less pronounced at 4.3 V compared to elevated charge cut-off voltages of 4.6 V. After a maximum of 100 cycles, we detected an overall transition metal loss of 0.2 wt‰ in relation to the whole cathode active material for cells cycled to 4.3 V. At an increased charge cut-off voltage of 4.6 V, 4.5 wt‰ transition metal loss in relation to the whole cathode active material could be detected. The corresponding transition metal dissolution induced capacity loss at the cathode could thus be attributed to 1.2 mAh g-1. Compared to the overall capacity loss of 80 mAh g-1 of the complete cell after 100 galvanostatic charge/discharge cycles the value is quite low. Hence, the overall full cell capacity fade cannot be assigned exclusively to the transition metal dissolution induced cathode fading.

  2. Spectroscopic and electronic structure studies of copper(II) binding to His111 in the human prion protein fragment 106-115: evaluating the role of protons and methionine residues.

    PubMed

    Rivillas-Acevedo, Lina; Grande-Aztatzi, Rafael; Lomelí, Italia; García, Javier E; Barrios, Erika; Teloxa, Sarai; Vela, Alberto; Quintanar, Liliana

    2011-03-07

    The prion protein (PrP(C)) is implicated in the spongiform encephalopathies in mammals, and it is known to bind Cu(II) at the N-terminal region. The region around His111 has been proposed to be key for the conversion of normal PrP(C) to its infectious isoform PrP(Sc). The principal aim of this study is to understand the role of protons and methionine residues 109 and 112 in the coordination of Cu(II) to the peptide fragment 106-115 of human PrP, using different spectroscopic techniques (UV-vis absorption, circular dichroism, and electron paramagnetic resonance) in combination with detailed electronic structure calculations. Our study has identified a proton equilibrium with a pK(a) of 7.5 associated with the Cu(II)-PrP(106-115) complex, which is ascribed to the deprotonation of the Met109 amide group, and it converts the site from a 3NO to a 4N equatorial coordination mode. These findings have important implications as they imply that the coordination environment of this Cu binding site at physiological pH is a mixture of two species. This study also establishes that Met109 and Met112 do not participate as equatorial ligands for Cu, and that Met112 is not an essential ligand, while Met109 plays a more important role as a weak axial ligand, particularly for the 3NO coordination mode. A role for Met109 as a highly conserved residue that is important to regulate the protonation state and redox activity of this Cu binding site, which in turn would be important for the aggregation and amyloidogenic properties of the protein, is proposed.

  3. Possible novel agents in marginal zone lymphoma.

    PubMed

    Zinzani, Pier Luigi; Broccoli, Alessandro

    Efficacy, safety and mechanisms of action of novel agents in marginal zone lymphoma patients, both with a nodal and extranodal presentation, are reviewed. Data on lenalidomide, bortezomib and (90)yttrium-ibrutumomab tiuxetan are obtained from trials specifically designed for patients affected by marginal zone lymphoma and with various disease presentations. The role of targeted agents, such as obinutuzumab, ibrutinib and idelalisib, and of some very new drugs (venetoclax, copanlisib, ublituximab and TGR-1202) is also discussed, taking into account the most relevant experiences in patients with indolent non-Hodgkin's lymphomas. A glance to some possible drug combinations will also be provided, along with an update of the most relevant ongoing trials.

  4. 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.

  5. 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.

  6. 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.

  7. Accumulation of indium-111-labeled granulocytes in malignant tumors

    SciTech Connect

    Schmidt, K.G.; Rasmussen, J.W.; Wedebye, I.M.; Frederiksen, P.B.; Pedersen, N.T.

    1988-04-01

    In a retrospective study of 220 (/sup 111/In)granulocyte scintigrams from 208 patients, 25 patients had malignant neoplasms. Among these, tumor uptake of /sup 111/In activity was observed in ten patients (intense activity in two patients with non-Hodgkin's lymphoma and colonic carcinoma, respectively; moderate uptake in a patient with non-Hodgkin's lymphoma, and in a patient with an ovarian carcinoma; weak activity in three patients with cerebral neoplasms; and activity within otherwise cold metastatic lesions of the liver in three patients). Microscopic investigation following specific granulocyte staining revealed the greatest extent of granulocyte infiltration in the tumors which took up /sup 111/In activity, emphasizing the importance of tumor granulocyte infiltration as the single most important factor underlying tumor accumulation of /sup 111/In activity during (/sup 111/In)granulocyte scintigraphy.

  8. 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.

  9. 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.

  10. Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of Neuroendocrine Tumors

    PubMed Central

    Deppen, Stephen A.; Liu, Eric; Blume, Jeffrey D.; Clanton, Jeffrey; Shi, Chanjuan; Jones-Jackson, Laurie B.; Lakhani, Vipul; Baum, Richard P.; Berlin, Jordan; Smith, Gary T.; Graham, Michael; Sandler, Martin P.; Delbeke, Dominique; Walker, Ronald C.

    2017-01-01

    Our purpose was to evaluate safety and efficacy of 68Ga-DOTATATE PET/CT compared with 111In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. Methods 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after 68Ga-DOTATATE injection. Added value was determined by changes in treatment plan when 68Ga-DOTATATE PET/CT results were added to all prior imaging, including 111In-pentetreotide. Interobserver reproducibility of 68Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. Results 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). 68Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. 68Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by 111In-pentetreotide. Conclusion 68Ga-DOTATATE PET/CT was equivalent or superior to 111In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. 68Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with 111In-pentetreotide, 68Ga-DOTATATE imaging should be used instead of 111In-pentetreotide imaging where available. PMID:26769865

  11. Loss of 111Indium as indicator of platelet injury

    SciTech Connect

    Joist, J.H.; Baker, R.K.

    1981-08-01

    We previously demonstrated that platelets can be labeled with 111Inoxine with high labeling efficiency and that 111In is not liberated from labeled platelets during the platelet release reaction or prolonged in vitro storage. In view of these findings, we examined the potential usefulness of loss of 111In from labeled platelets as an indicator of platelet damage by comparing the loss of 111In with that of 51Cr and LDH (in some experiments also with platelet factor 3 availability) under different conditions of platelet injury. When washed human platelets labeled with either 51Cr-chromate or 111In-oxine were exposed to increasing concentrations of detergents (Triton X-100, lysolecithin), threshold, rate, and extent of loss of 111In, 51Cr and, LDH were similar. In contrast, when labeled platelets were depleted of metabolic energy by incubation in glucose-free Tyrode albumin solution or glucose-depleted plasma in the presence of antimycin A and 2-deoxy-D-glucose, loss of 51Cr (and PF3a) occurred earlier and progressed at a faster rate than that of 111In or LDH. Similar results were obtained when platelets were exposed to increasing concentrations of PlA1 antibody, causing complement-mediated immune injury. The findings indicate that with certain agents that cause rapid platelet disruption (lysis), different platelet constituents are lost at similar rates. However, under conditions of more subtle or slowly progressive platelet injury, small molecules such as adenine nucleotides (51Cr) may escape earlier and at faster rates than larger molecules such as LDH or 111In-binding platelet protein. Thus, neither 111In loss nor LDH loss appear to be suitable indicators for sublytic or prelytic platelet injury.

  12. 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.

  13. 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.

  14. 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.

  15. Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein

    SciTech Connect

    Moerlein, S.M.; Daugherty, A.; Sobel, B.E.; Welch, M.J. )

    1991-02-01

    Low-density lipoprotein (LDL) labeled with either gallium-68 ({sup 68}Ga) or indium-111 ({sup 111}In) was evaluated as a potential PET or SPECT radiopharmaceutical for determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or {sup 111}In was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70% radiochemical yield. Studies in vivo that compared {sup 68}Ga- or {sup 111}In-DTPA-LDL with dilactitol-({sup 125}I)-tyramine LDL and 131I-LDL showed that both {sup 68}Ga- and {sup 111}In-labeled LDL behaved as residualizing radiotracers. Localization of radioactivity within the liver of normal rabbits was visualized clearly with ({sup 68}Ga)DTPA-LDL by PET and with ({sup 111}In)DTPA-LDL by gamma scintigraphy. Significant differences were observed in hepatic uptake of normal compared with hypercholesterolemic rabbits in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68 and {sup 111}In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive delineation of tissue LDL metabolism under normal and pathophysiologic conditions.

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

    PubMed

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

    2011-04-01

    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 (111)In ((111)In-IL-M1), along with control non-targeted liposomes ((111)In-CL). Incubation of (111)In-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 (111)In-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 (111)In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of (111)In-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.

  17. 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.

  18. Indium-111-labeled LDL: A potential agent for imaging atherosclerotic disease and lipoprotein biodistribution

    SciTech Connect

    Rosen, J.M.; Butler, S.P.; Meinken, G.E.; Wang, T.S.; Ramakrishnan, R.; Srivastava, S.C.; Alderson, P.O.; Ginsberg, H.N. )

    1990-03-01

    Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-({sup 111}In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-({sup 125}I) LDL binding to LDL receptors by {sup 111}In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of {sup 111}In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of {sup 111}In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that {sup 111}In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.

  19. 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.

  20. Dual isotope study of iodine-125 and indium-111-labeled antibody in athymic mice

    SciTech Connect

    Carney, P.L.; Rogers, P.E.; Johnson, D.K. )

    1989-03-01

    Monoclonal antibody B72.3 was coupled to a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA). The maximum substitution achievable without loss of immunoreactivity was three DTPA groups per immunoglobulin molecule. The resulting conjugate was labeled with {sup 111}In by brief incubation with {sup 111}InCl{sub 3}, giving a mean radiochemical yield of {sup 111}In-labeled antibody of 96%. The ({sup 111}In)B72.3 preparation was mixed with an ({sup 125}I) B72.3 preparation, obtained by the chloramine-T method, and the mixture administered to athymic mice bearing subcutaneous LS174T colon carcinoma xenografts. There were no significant differences (p greater than 0.1) in the biodistributions of the two labels at 1, 2, 5, and 7 days postinjection. These results are contrasted with prior studies showing elevated levels of {sup 111}In in liver, spleen, and kidneys using B72.3-DTPA conjugates prepared via the bicyclic anhydride. It is concluded that protein cross-linking and/or the formation of unstable chelate sites in anhydride coupled conjugates underlie these disparities.

  1. 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.

  2. Effect of acetylation on monoclonal antibody ZCE-025 Fab': Distribution in normal and tumor-bearing mice

    SciTech Connect

    Tarburton, J.P.; Halpern, S.E.; Hagan, P.L.; Sudora, E.; Chen, A.; Fridman, D.M.; Pfaff, A.E. )

    1990-04-01

    Studies were performed to determine in vitro and in vivo effects of acetylation on Fab' fragments of ZCE-025, a monoclonal anti-CEA antibody. Isoelectric focusing revealed a drop in isoelectric point of 1.7 pI units following acetylation. Biodistribution studies of acetylated and nonacetylated (111In)Fab' were performed in normal BALB/c mice and in nude mice bearing the T-380 CEA-producing human colon tumor. The acetylated fragments remained in the vascular compartment longer and had significantly diminished renal uptake of 111In compared to controls. While acetylation itself effected a 50% drop in immunoreactivity, tumor uptake of the acetylated and nonacetylated 111In-labeled Fab' fragments was comparable, with the exception of one data point, through 72 h.

  3. Indium-111 chloride imaging in the detection of infected prostheses

    SciTech Connect

    Sayle, B.A.; Fawcett, H.D.; Wilkey, D.J.; Cierny, G. III; Mader, J.T.

    1985-07-01

    Thirty-three patients with painful joint prostheses and a suspicion of infection were imaged with (/sup 111/In)chloride. A final diagnosis was established by culture in 19. Of these, 12 were categorized as true positives and three as true negatives. There were two false-positive studies, occurring in patients with knee prostheses. In both, the culture was obtained by aspiration. The sensitivity was 86%, specificity 60%, and accuracy 79%. Seventeen of the proven cases had bone imaging prior to (/sup 111/In)chloride imaging. All 17 static images were positive and were not helpful in differentiating loosening from infection. Using increased uptake on the blood-pool image as a criteria for infection, the sensitivity was 89%, but the specificity was 0. Adding flow studies made little difference in interpreting the blood-pool images. This study shows that (/sup 111/In)chloride imaging is more accurate in evaluating infection in prosthesis than bone imaging.

  4. 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

  5. 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.

  6. EGF-coated gold nanoparticles provide an efficient nano-scale delivery system for the molecular radiotherapy of EGFR-positive cancer

    PubMed Central

    Song, Lei; Falzone, Nadia; Vallis, Katherine A.

    2016-01-01

    Abstract Purpose Radiolabeled antibodies and peptides hold promise for molecular radiotherapy but are often limited by a low payload resulting in inadequate delivery of radioactivity to tumour tissue and, therefore, modest therapeutic effect. We developed a facile synthetic method of radiolabeling indium-111 (111In) to epidermal growth factor (EGF)-gold nanoparticles (111In-EGF-Au NP) with a high payload. Materials and methods EGF-Au NP were prepared via an interaction between gold and the disulphide bonds of EGF and radiolabeled using 111InCl3. Targeting efficiency was investigated by quantitating internalized radioactivity and by confocal imaging following exposure of MDA-MB-468 (1.3 × 106 EGFR/cell) and MCF-7 (104 EGFR/cell) cells to Cy3-EGF-Au NP. Cytotoxicity was evaluated in clonogenic assays. Results The proportion of total administered radioactivity that was internalized by MDA-MB-468 and MCF-7 cells was 15% and 1.3%, respectively (mixing ratio of EGF:Au of 160). This differential uptake in the two cell lines was confirmed using confocal microscopy. 111In-EGF-Au NP were significantly more radiotoxic to MDA-MB-468 than MCF-7 cells with a surviving fraction of 17.1 ± 4.4% versus 89.8 ± 1.4% (p < 0.001) after exposure for 4 h. Conclusions An 111In-labeled EGF-Au nanosystem was developed. It enabled targeted delivery of a high 111In payload specifically to EGFR-positive cancer cells leading to radiotoxicity that can be exploited for molecularly targeted radiotherapy. PMID:26999580

  7. 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.

  8. In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin-binding therapeutic affibody construct

    PubMed Central

    Bass, Tarek Z.; Rosestedt, Maria; Mitran, Bogdan; Frejd, Fredrik Y.; Löfblom, John; Tolmachev, Vladimir; Ståhl, Stefan; Orlova, Anna

    2017-01-01

    Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with 111In via a DOTA chelator. The residence time of 111In-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. 111In-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, 111In-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct 111In-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of 111In-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours. PMID:28230065

  9. 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

  10. 68Gallium-DOTATATE PET/CT Scanning Results in Patients with MEN1

    PubMed Central

    Sadowski, Samira M; Millo, Corina; Cottle-Delisle, Candice; Merkel, Roxanne; Yang, Lily A; Herscovitch, Peter; Pacak, Karel; Simonds, William F; Marx, Stephen J; Kebebew, Electron

    2015-01-01

    Background Screening for neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN1) is recommended to detect primary and metastatic tumors, which can result in significant morbidity and mortality. The utility of somatostatin receptor imaging 68Gallium-DOTATATE PET/CT in patients with MEN1 is not known. The aim of this study was to prospectively determine the accuracy of 68Gallium-DOTATATE PET/CT versus 111In-pentetreotide SPECT/CT and anatomic imaging in patients with MEN1. Study design Prospective study comparing 68Gallium-DOTATATE PET/CT, 111In-pentetreotide SPECT/CT, and triphasic CT scan to clinical, biochemical and pathological data in 26 patients with MEN1. Results 68Gallium-DOTATATE PET/CT detected 107 lesions; 111In- pentetreotide SPECT/CT detected 33 lesions; and CT scan detected 48 lesions. Lesions detected on 68Gallium-DOTATATE PET/CT had high SUVmax (median SUVmax = 72.8 [range 19–191]). In 7 of the 26 patients (27%), 68Gallium-DOTATATE PET/CT was positive with a negative 111In-pentetreotide SPECT/CT, and in 10 patients (38.5%), additional metastases were detected (range 0.3 cm to 1.5 cm). In 8 of the 26 patients (31%), there was a change in management recommendations as a result of the findings on 68Gallium-DOTATATE PET/CT that were not seen on 111In- pentetreotide SPECT/CT and CT scan. Conclusions 68Gallium-DOTATATE PET/CT is more sensitive for detecting NETs than 111In-pentetreotide SPECT/CT and CT scan in patients with MEN1. This imaging technique should be integrated into radiologic screening and surveillance of patients with MEN1, as it can significantly alter management recommendations. PMID:26206648

  11. ¹¹¹In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer.

    PubMed

    Fasih, Aisha; Fonge, Humphrey; Cai, Zhongli; Leyton, Jeffrey V; Tikhomirov, Ilia; Done, Susan J; Reilly, Raymond M

    2012-08-01

    Increased expression of epidermal growth factor receptors (EGFR) in breast cancer (BC) is often associated with trastuzumab (Herceptin)-resistant forms of the disease and represents an attractive target for novel therapies. Nimotuzumab is a humanized IgG(1) monoclonal antibody that is in clinical trials for treatment of EGFR-overexpressing malignancies. We show here that nimotuzumab derivatized with benzylisothiocyanate diethylenetriaminepentaacetic acid for labelling with the subcellular range Auger electron-emitter, (111)In and modified with nuclear translocation sequence (NLS) peptides ((111)In-NLS-Bn-DTPA-nimotuzumab) was bound, internalized and transported to the nucleus of EGFR-positive BC cells. Emission of Auger electrons in close proximity to the nucleus caused multiple DNA double-strand breaks which diminished the clonogenic survival (CS) of MDA-MB-468 cells that have high EGFR density (2.4 × 10(6) receptors/cell) to less than 3 %. (111)In-Bn-DTPA-nimotuzumab without NLS peptide modification was sevenfold less effective for killing MDA-MB-468 cells. (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification were equivalently cytotoxic to MDA-MB-231 and TrR1 BC cells that have moderate EGFR density (5.4 × 10(5) or 4.2 × 10(5) receptors/cell, respectively) reducing their CS by twofold. MDA-MB-231 cells have intrinsic trastuzumab resistance due to low HER2 density, whereas TrR1 cells have acquired resistance despite HER2 overexpression. Biodistribution and microSPECT/CT imaging revealed that (111)In-NLS-Bn-DTPA-nimotuzumab exhibited more rapid elimination from the blood and lower tumour uptake than (111)In-Bn-DTPA-nimotuzumab. Tumour uptake of the radioimmunoconjugates in mice with MDA-MB-468 xenografts was high (8-16 % injected dose/g) and was blocked by administration of an excess of unlabelled nimotuzumab, demonstrating EGFR specificity. We conclude that (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification are promising Auger

  12. 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.

  13. 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.

  14. 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

  15. Internal radiation dosimetry of orally administered radiotracers for the assessment of gastrointestinal motility.

    PubMed

    Yeong, Chai-Hong; Ng, Kwan-Hoong; Abdullah, Basri Johan Jeet; Chung, Lip-Yong; Goh, Khean-Lee; Perkins, Alan Christopher

    2014-12-01

    Radionuclide imaging using (111)In, (99m)Tc and (153)Sm is commonly undertaken for the clinical investigation of gastric emptying, intestinal motility and whole gut transit. However the documented evidence concerning internal radiation dosimetry for such studies is not readily available. This communication documents the internal radiation dosimetry for whole gastrointestinal transit studies using (111)In, (99m)Tc and (153)Sm labeled formulations. The findings were compared to the diagnostic reference levels recommended by the United Kingdom Administration of Radioactive Substances Advisory Committee, for gastrointestinal transit studies.

  16. 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.

  17. 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.

  18. 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.

  19. The "'Grammar Correction' Debate in L2 Writing": Where Are We, and Where Do We Go from Here?--(And What Do We Do in the Meantime ...?)

    ERIC Educational Resources Information Center

    Ferris, Dana R.

    2004-01-01

    The efficacy of teacher error/grammar correction in second language writing classes has been the subject of much controversy, including a published debate in an earlier volume of this journal [J. Second Language Writing 8 (1999) 1; J. Second Language Writing 8 (1999) 111]. In this paper, the state-of-the-art in error correction research in L2…

  20. 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).

  1. Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: Imaging of tumors hosted in nude mice

    SciTech Connect

    Le Doussal, J.M.; Gruaz-Guyon, A.; Martin, M.; Gautherot, E.; Delaage, M.; Barbet, J. )

    1990-06-01

    Antibody conjugates were prepared by coupling F(ab')2 or Fab' fragments of an antibody specific for the human high molecular weight-melanoma associated antigen to Fab' fragments of an antibody specific for indium-diethylenetriaminepentaacetate complexes. Monovalent and bivalent haptens were synthesized by reacting the dipeptide tyrosyl-lysine with diethylenetriaminepentaacetic cyclic anhydride. In vitro, the antibody conjugate mediated binding of the 111In-labeled haptens to melanoma cells. In vivo, it allowed specific localization of the haptens in A375 tumors. The bivalent hapten exhibited much higher efficiency at targeting 111In onto cells, both in vitro and in vivo. Antibody conjugate and hapten doses (2 micrograms and 1 pmol, respectively) and the delay between antibody conjugate and tracer injections (24 h) were adjusted to maximize tumor uptake (4% injected dose/g) and tumor to normal tissue contrast (greater than 3) obtained 3 h after injection of the 111In-labeled bivalent hapten. This two-step technique, when compared to direct targeting of 111In-labeled F(ab')2 fragments, provided lower localization of injected activity into the tumor (x 0.25), but higher tumor/tissue ratios, especially with respect to liver (x 7), spleen (x 8), and kidneys (x 10). In addition, high contrast images were obtained within 3 hours, instead of days. Thus, antibody conjugate-mediated targeting of small bivalent haptens, labeled with short half-life isotopes, is proposed as a general method for improving tumor radioimmunolocalization.

  2. 19 CFR 111.29 - Diligence in correspondence and paying monies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Diligence in correspondence and paying monies. 111... in correspondence and paying monies. (a) Due diligence by broker. Each broker must exercise due diligence in making financial settlements, in answering correspondence, and in preparing or assisting in...

  3. 19 CFR 111.29 - Diligence in correspondence and paying monies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Diligence in correspondence and paying monies. 111... in correspondence and paying monies. (a) Due diligence by broker. Each broker must exercise due diligence in making financial settlements, in answering correspondence, and in preparing or assisting in...

  4. 19 CFR 111.29 - Diligence in correspondence and paying monies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Diligence in correspondence and paying monies. 111... in correspondence and paying monies. (a) Due diligence by broker. Each broker must exercise due diligence in making financial settlements, in answering correspondence, and in preparing or assisting in...

  5. 19 CFR 111.29 - Diligence in correspondence and paying monies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Diligence in correspondence and paying monies. 111... in correspondence and paying monies. (a) Due diligence by broker. Each broker must exercise due diligence in making financial settlements, in answering correspondence, and in preparing or assisting in...

  6. 19 CFR 111.29 - Diligence in correspondence and paying monies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Diligence in correspondence and paying monies. 111... in correspondence and paying monies. (a) Due diligence by broker. Each broker must exercise due diligence in making financial settlements, in answering correspondence, and in preparing or assisting in...

  7. 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

  8. Standardized Screening and Assessment of Older Emergency Department Patients: A Survey of Implementation in Quebec

    ERIC Educational Resources Information Center

    McCusker, Jane; Verdon, Josee; Veillette, Nathalie; Berg, Katherine; Emond, Tina; Belzile, Eric

    2007-01-01

    Cost-effective methods have been developed to help busy emergency department (ED) staff cope with the growing number of older patients, including quick screening and assessment tools to identify those at high risk and note their specific needs. This survey, from a sample of key informants from all EDs (n=111) in the province of Quebec…

  9. 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.

  10. Advising Foreign Security Forces: Implications of Korea and Vietnam

    DTIC Science & Technology

    2010-12-02

    the requirements for successful foreign internal defense operations.”111 In early-2008, Army Special Forces Lieutenant Colonel John Mulberry argued...purpose force is robust enough to execute any advisory effort with little preparation. Similar to Maxwell, Mulberry makes a case for the...April 2009), While Mulberry argues that foreign internal defense http

  11. 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.

  12. Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging.

    PubMed

    Kojima, Chie; Niki, Yuichiro; Ogawa, Mikako; Magata, Yasuhiro

    2014-12-10

    Polymers are widely applied to drug delivery systems because polymers are generally excreted from the body more slowly than small molecules. Subcutaneous injection is one plausible means of administration. In this study, the in vivo behaviors of subcutaneously injected polymers, linear poly(glutamic acid) (Poly-Glu), acetylated dendrimer (Ac-den) and collagen peptide-conjugated dendrimer (CP-den), were investigated. Single photon emission computed tomography (SPECT) imaging was used to noninvasively monitor the in vivo behaviors. Diethylenetriaminepentaacetic acid (DTPA) was conjugated to these polymers, which were labeled with radioactive (111)In. These (111)In-DTPA-bearing polymers (Poly-Glu-DTPA, Ac-den-DTPA and CP-den-DTPA) and unconjugated DTPA were subcutaneously injected into tumor-bearing mice, which were subjected to SPECT imaging. These (111)In-DTPA-bearing polymers were largely retained at the injection site for at least 1 day, whereas the unconjugated DTPA was rapidly cleared from the whole body through excretion. Poly-Glu-DTPA and Ac-den-DTPA were partly accumulated in the kidney (and the liver), but the CP-den-DTPA was not. However, these (111)In-DTPA-bearing polymers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected polymers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site.

  13. 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.…

  14. High efficiency diffusion molecular retention tumor targeting.

    PubMed

    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) In(3+)), 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 i.v. methods was assessed by surface fluorescence, biodistribution of [(111)In] RGD and [(111)In] 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 [(111)In] 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 i.v.). 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.

  15. US EPA, Pesticide Product Label, , 01/03/1983

    EPA Pesticide Factsheets

    2011-04-21

    ... n'T('.lll ~·.I·'·~· 1'1,·' I ',III! !"l .. ·.!l·tI'PI ,~p or Sp,.I), 11(',1In'I",1 ,'. \\I~"11 'I, !',I!'\\ " , 11 .II,{, .. ... p(" aCH'1 /lpply II f.llI t··" RASPBERRIES: Spur Blight. ...

  16. 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.

  17. 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)

  18. Indium-based and iodine-based labeling of HPMA copolymer–epirubicin conjugates: Impact of structure on the in vivo fate

    PubMed Central

    Zhang, Libin; Zhang, Rui; Yang, Jiyuan; Wang, Jiawei; Kopeček, Jindřich

    2016-01-01

    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) 111In-2P-EPI-125I (polymeric carrier 2P was radiolabeled with 111In and drug EPI with 125I), and 2) 125I-2P-EPI-111In (polymeric carrier 2P was radiolabeled with 125I and drug EPI with 111In). 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 (111In-2P and 125I-2P) showed similar retention of radioactivity in both tumor and major organs except kidney. However, compared to 111In-labeled payload EPI, 125I-labeled EPI showed lower radioactivity in normal organs and tumor at 48 h and 144 h 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)111In than EPI(Tyr)125I was observed. It may be also due to in vivo catabolism and subsequent iodine loss as

  19. 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

  20. 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

  1. Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas.

    PubMed

    Brom, Maarten; Joosten, Lieke; Oyen, Wim J G; Gotthardt, Martin; Boerman, Otto C

    2012-01-01

    Internalizing agonists are usually selected for peptide receptor targeting. 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 with the GLP-1R agonists exendin-3 and exendin-4. The binding and internalization kinetics of labelled [Lys(40) (DTPA)]exendin-3, [Lys(40) (DTPA)]exendin-4 and [Lys(40) (DTPA)]exendin(9-39) were determined in vitro using INS-1 cells. The in vivo targeting properties of [Lys(40) ((111) In-DTPA)]exendin-3, [Lys(40) ((111) In-DTPA)]exendin-4 and [Lys(40) ((111) In-DTPA)]exendin(9-39) were examined in BALB/c nude mice with subcutaneous INS-1 tumours. (nat) In-labelled [Lys(40) (DTPA)]exendin-3, [Lys(40) (DTPA)]exendin-4 and [Lys(40) (DTPA)]exendin(9-39) exhibited similar IC(50) values (13.5, 14.4 and 13.4 n m, respectively) and bound to 26 × 10(3) , 41 × 10(3) and 37 × 10(3) receptors per cell, respectively. [Lys(40) ((111) In-DTPA)]exendin-3 and [Lys(40) ((111) In-DTPA)]exendin-4 showed rapid in vitro binding and internalization kinetics, whereas [Lys(40) ((111) In-DTPA)]exendin(9-39) showed lower binding and minimal internalization in vitro. In mice, high specific uptake of [Lys(40) ((111) In-DTPA)]exendin-3 [25.0 ± 6.0% injected dose (ID) g(-1) ] in the tumour was observed at 0.5 h post-injection (p.i.) with similar uptake up to 4 h p.i. [Lys(40) ((111) In-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(-1), respectively). Remarkably, [Lys(40) ((111) In-DTPA)]exendin(9-39) showed only low specific uptake in the tumour at 0.5 h p.i. (3.2 ± 0.7% ID g(-1)), rapidly decreasing over time. In conclusion, the GLP-1R agonists [Lys(40) (DTPA)]exendin-3 and [Lys(40) (DTPA)]exendin-4 labelled with (111

  2. Quantitative assessment of overall inflammatory bowel disease activity using labelled leucocytes: a direct comparison between indium-111 and technetium-99m HMPAO methods.

    PubMed Central

    Mansfield, J C; Giaffer, M H; Tindale, W B; Holdsworth, C D

    1995-01-01

    The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method. Images Figure 2 PMID:8549945

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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)

  9. Recent developments of cyclotron produced radionuclides for nuclear cardiology

    NASA Astrophysics Data System (ADS)

    Kulkarni, P. V.; Jansen, D. E.; Corbett, J. R.

    1987-04-01

    For over a decade myocardial perfusion imaging with thallium-201, a cyclotron product, has been routinely used in clinical medicine. Recent advances have allowed the efficient production of very high purity (> 99.8%) iodine-123. New metabolically active 123I labeled radiopharmaceuticals, including alkyl and phenyl fatty acids, and norepinephrine analogs, have been developed and are undergoing clinical trials. Fab' fragments of monoclonal antibodies to cardiac myosin have been labeled with indium-111 ( 111In) and are undergoing clinical evaluation for imaging myocardial infarcts. Monoclonal antibodies to platelets, fibrin, and the thrombolytic agent, tissue plasminogen activator (TPA), have recently been labeled with 111In. Together these developments in radiotracers and instrumentation should have a significant impact on the future of cardiovascular nuclear medicine. This manuscript will discuss developments in single photon emitting radiotracers for myocardial imaging.

  10. Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer.

    PubMed

    Robu, Stephanie; Schottelius, Margret; Eiber, Matthias; Maurer, Tobias; Gschwend, Jürgen; Schwaiger, Markus; Wester, Hans-Jürgen

    2017-02-01

    Initial studies in patients have demonstrated the suitability of (111)In-PSMA-I&T ((111)In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostate-specific membrane antigen and I&T is imaging and therapy) for radioguided surgery (RGS) of small metastatic prostate cancer (PCa) soft-tissue lesions. To meet the clinical need for a more cost-effective alternative, the PSMA-I&T-based tracer concept was adapted to (99m)Tc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine- (MAS3) and all-D-serine- (mas3) chelating moieties were evaluated in parallel, and a kit procedure for routine (99m)Tc labeling was developed.

  11. 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

  12. 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

  13. [Radionuclide imaging of neurendocrine tumors: biological basis and diagnostic results].

    PubMed

    Genovese, Eugenio Annibale; Mallardo, Vania; Rossi, Michele; Vaccaro, Andrea; Raucci, Antonio; Della Vecchi, Nicoletta; Romano, Giovanna; Califano, Teresa; Schillirò, Francesco

    2013-01-01

    Many radiopharmaceuticals have been successfully used in nuclear medicine to detect neuroendocrine tumors, and many of them are based on a specific mechanism of uptake, while others are non-specific probes. This "review" focuses on the clinical applications of metaiodobenzylguanidine, (111)In-pentreotide and positron emission tomography (PET) tracers. New avances in diagnostic imaging will be discussed. Molecular imaging serves these diagnostic functions and provides powerful means for non-invasively detecting disease.

  14. 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.

  15. Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats

    SciTech Connect

    Abrams, M.J.; Juweid, M.; tenKate, C.I.; Schwartz, D.A.; Hauser, M.M.; Gaul, F.E.; Fuccello, A.J.; Rubin, R.H.; Strauss, H.W.; Fischman, A.J. )

    1990-12-01

    The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m ({sup 99m}Tc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: ({sup 99m}Tc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. {sup 111}In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: {sup 99m}Tc-IgG greater than {sup 111}In-IgG in lung, liver, and spleen; {sup 99m}Tc-IgG less than {sup 111}In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with {sup 99m}Tc via a nicotinyl hydrazine modified intermediate is equivalent to {sup 111}In-IgG for imaging focal sites of infection in experimental animals.

  16. Sequential assessment of pulmonary epithelial diethylene triamine penta-acetate clearance and intrapulmonary transferrin accumulation during Escherichia coli peritonitis

    SciTech Connect

    Ishizaka, A.; Stephens, K.E.; Segall, G.M.; Hatherill, J.R.; McDougall, I.R.; Wu, Z.; Raffin, T.A. )

    1990-03-01

    The individual roles of pulmonary capillary endothelial and alveolar epithelial permeability in the pathogenesis of the adult respiratory distress syndrome (ARDS) are unclear. We developed a method for the sequential assessment of pulmonary macromolecule accumulation and small solute clearance in vivo using a gamma camera. We measured the exponential clearance coefficient of 111In-labeled diethylene triamine penta-acetate (111In-DTPA) to assess airway clearance of small solutes. We also calculated the exponential equilibration coefficient of 111In-labeled transferrin (111In-TF) to assess intrapulmonary accumulation of transferrin. We determined these parameters in guinea pigs with Escherichia coli peritonitis and compared them with a saline-treated control group, oleic-acid-treated groups, and a group treated with low molecular weight dextran Ringer solution. The pulmonary DTPA clearance and the intrapulmonary transferrin accumulation were significantly increased in the peritonitis group (29.4 +/- 8.2 x 10(-3) min-1, p less than 0.02, and 15.1 +/- 3.1 x 10(-3) min-1, p less than 0.02) when compared with the control group (3.1 +/- 0.8 x 10(-3) min-1 and 4.5 +/- 0.5 x 10(-3) min-1). These changes developed within 5.5 h of the initial insult. Neither increased extravascular lung water nor elevated pulmonary artery and left atrial pressures were detected in the peritonitis group. The low molecular weight dextran Ringer group did not show a significant increase in the pulmonary DTPA clearance and the intrapulmonary transferrin accumulation.

  17. 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.

  18. Suppression by intradermal administration of heparin of eosinophil accumulation but not oedema formation in inflammatory reactions in guinea-pig skin.

    PubMed Central

    Teixeira, M. M.; Hellewell, P. G.

    1993-01-01

    1. Heparin is widely used in the treatment of thrombotic disorders and as an aid in surgery. Anti-inflammatory effects of heparin have also been described. In this study, we have investigated the effects of locally-injected heparin on the oedema formation and eosinophil accumulation induced by various inflammatory stimuli in guinea-pig skin. 2. Heparin dose-dependently suppressed the accumulation of 111In-labelled eosinophils induced by i.d. injection of zymosan-activated plasma (ZAP). The 111In-eosinophil accumulation induced by other inflammatory stimuli (compound 48/80, platelet activating factor, interleukin-8 and in a passive cutaneous anaphylaxis reaction) was also suppressed by locally-injected heparin. 3. Oedema formation in response to these same stimuli was not altered by the local injection of heparin. 4. Fucoidin, a negatively-charged sulphated algal polymer, had no effect on the 111In-eosinophil accumulation or oedema formation induced by ZAP. Nevertheless, fucoidin significantly suppressed the oedema formation induced by i.d. injection of cationic protein-containing extracts of Schistosoma mansoni larvae. Heparin also inhibited oedema induced by the extracts, suggesting that both fucoidin and heparin were effectively neutralizing the cationic protein of the extracts to inhibit their oedema-inducing activity. 5. Thus, heparin significantly inhibited the accumulation of 111In-eosinophils, but not oedema formation, induced by various inflammatory stimuli. This, taken together with the lack of effect of fucoidin, suggests that heparin interferes with the process of eosinophil trafficking by a mechanism that does not depend on neutralisation of the charge of the stimulatory molecules. PMID:8306092

  19. 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.

  20. 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.

  1. Preclinical evaluation of 68Ga-DOTA-minigastrin for the detection of cholecystokinin-2/gastrin receptor-positive tumors.

    PubMed

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J G; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C

    2011-04-01

    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.

  2. 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.

  3. Compendium of Animal Rabies Control, 1998. Vol. 47, No. RR-9

    DTIC Science & Technology

    1998-05-29

    offspring of wild animals crossbred to domestic dogs and cats) has not been established, and no rabies vaccine is licensed for these animals. Zoos or...animals. Such procedures in the United States have re- duced laboratory-confirmed rabies cases in dogs from 6,949 in 1947 to 111 in 1996. Because more... rabies cases are reported annually involving cats than dogs , vaccination of cats should be required. The recommended vaccination proce- dures and the

  4. 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.

  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. Principles of Strategic Communication for a New Global Commons

    DTIC Science & Technology

    2008-06-06

    Wadsworth Publishers, 1996. “Logic as Semiotic: The Theory of Signs.” The Philosophical Writings of Peirce . Edited by Justus Buchler. Mineola, NY...from the work of Berlo, Peirce , and Schramm, explains communication as a process through which a sender intends to send a combination of message and...important.111 In addition, communicative acts will drive and be driven by Clausewitz’s theories of interaction in war. He cites three cases of

  7. 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.

  8. Controlling the Electronic Structure of Graphene Using Surface-adsorbate Interactions

    DTIC Science & Technology

    2015-07-21

    before and after adsorption [in Fig. 4(a)] and structural changes to Gr/Ni(111) [in Fig. 4(b)]. Before adsorption, the atomic orbitals of graphene (pz...RAPID COMMUNICATIONS PHYSICAL REVIEW B 92, 041407(R) (2015) Controlling the electronic structure of graphene using surface-adsorbate interactions...manuscript received 3 May 2015; published 21 July 2015) Hybridization of atomic orbitals in graphene on Ni(111) opens up a large energy gap of ≈2.8 eV

  9. 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

    2015-07-03

    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.

  10. Dual labeling of lipopolysaccharides for SPECT-CT imaging and fluorescence microscopy.

    PubMed

    Duheron, Vincent; Moreau, Mathieu; Collin, Bertrand; Sali, Wahib; Bernhard, Claire; Goze, Christine; Gautier, Thomas; Pais de Barros, Jean-Paul; Deckert, Valérie; Brunotte, François; Lagrost, Laurent; Denat, Franck

    2014-03-21

    Lipopolysaccharides (LPS) or endotoxins are amphipathic, pro-inflammatory components of the outer membrane of Gram-negative bacteria. In the host, LPS can trigger a systemic inflammatory response syndrome. To bring insight into in vivo tissue distribution and cellular uptake of LPS, dual labeling was performed with a bimodal molecular probe designed for fluorescence and nuclear imaging. LPS were labeled with DOTA-Bodipy-NCS, and pro-inflammatory properties were controlled after each labeling step. LPS were then radiolabeled with (111)In and subsequently injected intravenously into wild-type, C57B16 mice, and their in vivo behavior was followed by single photon emission computed tomography coupled with X-ray computed tomography (SPECT-CT) and fluorescence microscopy. Time course of liver uptake of radiolabeled LPS ((111)In-DOTA-Bodipy-LPS) was visualized over a 24-h period in the whole animal by SPECT-CT. In complementary histological analyses with fluorescent microscopy, the bulk of injected (111)In-DOTA-Bodipy-LPS was found to localize early within the liver. Serum kinetics of unlabeled and DOTA-Bodipy-labeled LPS in mouse plasma were similar as ascertained by direct quantitation of β-hydroxymyristate, and DOTA-Bodipy-LPS was found to retain the potent, pro-inflammatory property of the unlabeled molecule as assessed by serum cytokine assays. It is concluded that the dual labeling process, involving the formation of covalent bonds between a DOTA-Bodipy-NCS probe and LPS molecules is relevant for imaging and kinetic analysis of LPS biodistribution, both in vivo and ex vivo. Data of the present study come in direct and visual support of a lipopolysaccharide transport through which pro-inflammatory LPS can be transported from the periphery to the liver for detoxification. The (111)In-DOTA-Bodipy-LPS probe arises here as a relevant tool to identify key components of LPS detoxification in vivo.

  11. Indium 111 toxicity in the human lymphocyte

    SciTech Connect

    Silberstein, E.B.; Watson, S.; Mayfield, G.; Kereiakes, J.G.; Bullock, W.

    1985-05-01

    Indium-labeled lymphocytes were examined for response to a variety of mitogens, ability to synthesize immunoglobulins, mitotic index, and presence of chromosome aberrations at a range of exposures from 0.2 to 500 muCi/10(8) cells. Results of all four tests were found to be abnormal when the lymphocytes were labeled with /sup 111/In activities well within those employed for diagnostic testing.

  12. Advantage of indium-111 leukocytes over ultrasound in imaging an infected renal cyst

    SciTech Connect

    Fortner, A.; Taylor, A. Jr.; Alazraki, N.; Datz, F.L.

    1986-07-01

    Indium-111-labeled leukocyte scanning is a highly sensitive and specific method of detecting abscesses. This report describes a patient with polycystic kidneys and a single infected cyst. Ultrasound could not determine which cyst was infected, but the infected cyst could be localized by (/sup 111/In)leukocyte imaging in conjunction with a (/sup 99m/Tc)DMSA renal scan. The two radionuclide studies were used to identify an infected renal cyst and direct ultrasound guided aspiration.

  13. Charlie, Development of a Light-Weight, Virtual Reality Trainer for the LSO Community: Time to Make the Leap Toward Immersive VR

    DTIC Science & Technology

    2015-09-01

    Trainer, Device 2H111, in which the LSO receives a series of six one-hour long sessions. For many LSOs, this will be the only interaction will this...fulfillment of the requirements for the degree of MASTER OF SCIENCE IN COMPUTER SCIENCE from the NAVAL POSTGRADUATE SCHOOL SEPTEMBER 2015...Department of Computer Science iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT Landing Signal Officers (LSOs) are the backbone of tailhook naval

  14. 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.

  15. 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.

  16. 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.

  17. Encapsulation, with high efficiency, of radioactive metal ions in liposomes.

    PubMed

    Hwang, K J; Merriam, J E; Beaumier, P L; Luk, K F

    1982-05-05

    The encapsulation of radioactive metalic cations, such as 111In3+ or 67Ga3+, in the internal aqueous compartment of liposomes can be achieved with an efficiency of about 90%. The efficient loading of a high specific activity of cations into liposomes involves the transport of 111In3+ or 67Ga3+ through the lipid bilayer to an encapsulated strong chelate, such as nitrilotriacetic acid, by 8-hydroxyquinoline, in conjunction with an efficient anion-exchange resin technique for the removal of the external cations. The efficiency of loading cations to liposomes is affected markedly by the concentration of 8-hydroxyquinoline-metal, and the presence of the chelating agents in the loading incubation mixture. However, the loading efficiency is not affected by the pH of the internal aqueous compartment of liposomes over a range of pH 5-9, the concentration of the liposomes, the method of liposomal preparation, the lamellar structure of the liposomes, and the composition of liposomes. Furthermore, the loading procedures do not appear to affect the size and the permeability of liposomes. There is a good agreement in the tissue distributions of the liposomes prepared by the present loading methods and those by the conventional method of encapsulation by sonication. Liposomes entrapping high specific activity of 67Ga3+ or 111In3+ will be useful for future studies of the in vivo kinetics of liposomes by the combined techniques of scintigraphic imaging and the gamma-ray perturbed angular correlation.

  18. 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.

  19. Histogram analysis of pharmacokinetic parameters by bootstrap resampling from one-point sampling data in animal experiments.

    PubMed

    Takemoto, Seiji; Yamaoka, Kiyoshi; Nishikawa, Makiya; Takakura, Yoshinobu

    2006-12-01

    A bootstrap method is proposed for assessing statistical histograms of pharmacokinetic parameters (AUC, MRT, CL and V(ss)) from one-point sampling data in animal experiments. A computer program, MOMENT(BS), written in Visual Basic on Microsoft Excel, was developed for the bootstrap calculation and the construction of histograms. MOMENT(BS) was applied to one-point sampling data of the blood concentration of three physiologically active proteins ((111)In labeled Hsp70, Suc(20)-BSA and Suc(40)-BSA) administered in different doses to mice. The histograms of AUC, MRT, CL and V(ss) were close to a normal (Gaussian) distribution with the bootstrap resampling number (200), or more, considering the skewness and kurtosis of the histograms. A good agreement of means and SD was obtained between the bootstrap and Bailer's approaches. The hypothesis test based on the normal distribution clearly demonstrated that the disposition of (111)In-Hsp70 and Suc(20)-BSA was almost independent of dose, whereas that of (111)In-Suc(40)-BSA was definitely dose-dependent. In conclusion, the bootstrap method was found to be an efficient method for assessing the histogram of pharmacokinetic parameters of blood or tissue disposition data by one-point sampling.

  20. In vivo tracing of indium-111 oxine-labeled human peripheral blood mononuclear cells in patients with lymphatic malignancies

    SciTech Connect

    Mueller, C.Z.; Zielinski, C.C.; Linkesch, W.; Ludwig, H.; Sinzinger, H.

    1989-06-01

    The in vivo migration of (/sup 111/In)oxine-labeled peripheral mononuclear cells (PMNC) was studied in 20 patients with various lymphatic malignancies and palpable enlarged lymph nodes. The maximal labeling dose of 10 microCi (0.37 MBq) (/sup 111/In)oxine/10(8) PMNC was found not to adversely influence either cell viability or lymphocyte proliferation in vitro. For in vivo studies, 1.5 X 10(9) PMNC were gained by lymphapheresis and reinjected intravenously after radioactive labeling, 150 microCi (5.55 MBq). The labeling of enlarged palpable lymph nodes was achieved in three out of three patients with Hodgkin's disease and in five out of five with high-malignant lymphoma, whereas three out of seven patients with low malignant lymphoma and no patient with chronic lymphatic leukemia had positive lymph node imaging. We thus conclude that PMNC retain their ability to migrate after (/sup 111/In)oxine labeling and that these cells traffic to involved lymph nodes of some, but not all hematologic malignancies.

  1. Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL® and 90Y-Lactosome for orthotopic mammary tumor

    NASA Astrophysics Data System (ADS)

    Kurihara, Kensuke; Ueda, Motoki; Hara, Isao; Hara, Eri; Sano, Kohei; Makino, Akira; Ozeki, Eiichi; Yamamoto, Fumihiko; Saji, Hideo; Togashi, Kaori; Kimura, Shunsaku

    2016-05-01

    Polymeric micelles (Lactosome) in the size of 20-30 nm were labeled with radionuclides of 111In (111In-DOTA-Lactosome) for SPECT imaging and 90Y (90Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of 111In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of 90Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of 90Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of 90Y-DOTA-Lactosome and DOXIL® inhibited the tumor growth during 15 days with their administrations.

  2. 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

  3. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition.

    PubMed

    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 [111In]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 [111In]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 [111In]WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation.

  4. Indium-111 T101 monoclonal antibody is superior to iodine-131 T101 in imaging of cutaneous T-cell lymphoma

    SciTech Connect

    Carrasquillo, J.A.; Mulshine, J.L.; Bunn, P.A. Jr.; Reynolds, J.C.; Foon, K.A.; Schroff, R.W.; Perentesis, P.; Steis, R.G.; Keenan, A.M.; Horowitz, M.

    1987-03-01

    We have reported that (/sup 111/In)T101 is highly effective in the detection of cutaneous T-cell lymphoma (CTCL) in nodal and cutaneous (erythroderma and tumor) sites. This study compares the biodistribution of (/sup 131/I)T101 (1 to 7.1 mg, 2 mCi) in four patients with CTCL; two of these patients also received (/sup 111/In)T101 (1 mg, 5 mCi). There was rapid clearance of (/sup 131/I)T101 from whole-body, spleen, liver, and bone marrow, with evidence of loss of /sup 131/I tracer from the T101. Lymph node uptake was minimal in three of four patients, and there was no localization in skin lesions. This contrasted with (/sup 111/In)T101 where there was prolonged retention of activity in these organs and excellent uptake in skin tumors, erythroderma, and lymph nodes. The study showed that (/sup 131/I)T101 was suboptimal for imaging CTCL patients and demonstrates that the isotope or labeling method can dramatically alter the apparent biodistribution and tumor targeting of a given monoclonal antibody.

  5. Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia

    SciTech Connect

    Panzer, S.; Lechner, K.; Neumann, E.; Meryn, S.; Haubenstock, A.

    1986-07-15

    In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous /sup 111/In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of /sup 111/In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of /sup 111/In-labeled platelets in nonsplenectomized patients suggests hypersplenism with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

  6. 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

  7. 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

    2015-10-22

    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.

  8. 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

  9. 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

  10. (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

  11. Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation.

    PubMed

    Yim, Cheng-Bin; Dijkgraaf, Ingrid; Merkx, Remco; Versluis, Cees; Eek, Annemarie; Mulder, Gwenn E; Rijkers, Dirk T S; Boerman, Otto C; Liskamp, Rob M J

    2010-05-27

    Herein, we describe the design, synthesis, and biological evaluation of a series of DOTA-conjugated monomeric, dimeric, and tetrameric [Tyr(3)]octreotide-based analogues as a tool for tumor imaging and/or radionuclide therapy. These compounds were synthesized using a Cu(I)-catalyzed 1,3-dipolar cycloaddition ("click" reaction) between peptidic azides and dendrimer-derived alkynes and a subsequent metal-free introduction of DOTA via the thio acid/sulfonyl azide amidation ("sulfo-click" reaction). In a competitive binding assay using rat pancreatic AR42J tumor cells, the monomeric [Tyr(3)]octreotide conjugate displayed the highest binding affinity (IC(50) = 1.32 nM) followed by dimeric [Tyr(3)]octreotide (2.45 nM), [DOTA(0),Tyr(3)]octreotide (2.45 nM), and tetrameric [Tyr(3)]octreotide (14.0 nM). Biodistribution studies with BALB/c nude mice with subcutaneous AR42J tumors showed that the (111)In-labeled monomeric [Tyr(3)]octreotide conjugate had the highest tumor uptake (42.3 +/- 2.8 %ID/g) at 2 h p.i., which was better than [(111)In-DOTA(0),Tyr(3)]octreotide (19.5 +/- 4.8 %ID/g). The (111)In-labeled dimeric [Tyr(3)]octreotide conjugate showed a long tumor retention (25.3 +/- 5.9 %ID/g at 2 h p.i. and 12.1 +/- 1.3 %ID/g at 24 h p.i.). These promising results can be exploited for therapeutic applications.

  12. Rat testis as a radiobiological in vivo model for radionuclides.

    PubMed

    Grafström, G; Jönsson, B-A; El Hassan, A M; Tennvall, J; Strand, S-E

    2006-01-01

    The radiobiological effect of intracellularly localised radionuclides emitting low energy electrons (Auger electrons) has received much attention. Most in vivo studies reported have been performed in the mouse testis. We have investigated the rat testis as an in vivo radiobiological model, with sperm-head survival, testis weight loss and also alteration in the blood plasma hormone levels of FSH and LH as radiobiological endpoints. Validation of the rat testis model was evaluated by using mean absorbed doses of up to 10 Gy from intratesticularly (i.t.) injected (111)In oxine or local X-ray irradiation. Biokinetics of the i.t. injected radionuclide was analysed by scintillation camera imaging and used in the absorbed dose estimation. By the analysis of the autoradiographs, the activity distribution was revealed. Cell fractionation showed (111)In to be mainly associated with the cell nuclei. External irradiations were monitored by thermoluminescence dosimeters. The sperm-head survival was the most sensitive radiobiological parameter correlated to the mean absorbed dose, with a D(37) of 2.3 Gy for (111)In oxine and 1.3 Gy for X rays. The levels of plasma pituitary gonadal hormones FSH and LH were elevated for absorbed doses >7.7 Gy. This investigation shows that the radiobiological model based on the rat testis has several advantages compared with the previously commonly used mouse testis model. The model is appropriate for further investigations of basic phenomena such as radiation geometry, intracellular kinetics and heterogeneity, crucial for an understanding of the biological effect of low-energy electrons.

  13. 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).

  14. 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).

  15. Prevention of ischemia-induced myocardial platelet deposition by exogenous prostacyclin

    SciTech Connect

    Aherne, T.; Price, D.C.; Yee, E.S.; Hsieh, W.R.; Ebert, P.A.

    1986-07-01

    The antithrombotic effects of prostacyclin infusion on myocardial platelet deposition were studied in a canine model during and after global ischemia. Eleven isolated heart preparations were subjected to 1 hour of cardioplegic arrest under moderate hypothermia (27 to 28/sup 0/C), including a control group (n = 7) and a prostacyclin-treated group (n = 4). The hearts of four other dogs were continuously perfused for 180 minutes. Platelet deposition was measured at 15 minute intervals throughout the 3 hour study. Serial full-thickness myocardial biopsy specimens were analyzed for activity of /sup 111/In-labeled platelets with /sup 99m/Tc-labeled erythrocyte correction for tissue blood content. The pattern of platelet distribution was determined by scintiscans of each heart, taken with a gamma camera at the end of the 60 minute reperfusion period. Substantial myocardial platelet deposition was found in the control hearts after ischemia but not in the prostacyclin-treated group (p less than 0.05). Furthermore, prostacyclin infusion had a significant disaggregatory effect on intracoronary platelet deposits when the precardioplegic and postcardioplegic biopsy specimens were analyzed (p less than 0.05). Three hours of continuous perfusion did not increase tissue /sup 111/In-labeled platelet activity. Ex vivo images showed platelet deposition to be a diffuse patchy process with significantly more /sup 111/In activity in the endocardium than in the epicardium after global ischemia (p less than 0.05). These data show the potent antithrombotic properties of prostacyclin in preventing and disaggregating ischemia-induced intracoronary platelet deposition during and after cardioplegic arrest.

  16. Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents

    PubMed Central

    Hernandez, Reinier; Heskamp, Sandra; Rijpkema, Mark; Bos, Desirée L.; Goldenberg, David M.; McBride, William J.; Morgenstern, Alfred; Bruchertseifer, Frank; Cai, Weibo; Boerman, Otto C.

    2017-01-01

    Despite the large interest in nuclear/optical multimodality imaging, the effect of radiation on the fluorescence of fluorophores remains largely unexplored. Herein, we report on the radiobleaching of cyanine fluorophores and describe conditions to provide robust radioprotection under practical (pre)clinical settings. We determined the radiosensitivity of several cyanine fluorescent compounds, including IRDye 800CW (800CW) and a dual modality imaging tetrapeptide containing DOTA as chelator and Dylight 800 as fluorophore, exposed to increasing activities of 111In, 68Ga, or 213Bi (γ, EC/β, and α emitter, respectively). An activity and type of radiation-dependent radiation-induced loss of fluorescence, radiobleaching, of 800CW was observed upon incubation with escalating activities of 111In, 68Ga, or 213Bi. 68Ga showed the largest radiolytic effect, followed by 111In and 213Bi. The addition of oxygen radical scavengers including ethanol, gentisic acid, and ascorbic acid (AA), provided a concentration dependent radioprotective effect. These results supported the hypothesis of a free radical-mediated radiobleaching mechanism. AA provided the most robust radioprotection over a wide range of concentrations and preserved fluorescence at much higher radioactivity levels. Overall, both near-infrared fluorescent compounds displayed similar sensitivity, except for 213Bi-irradiated solutions, where the dual modality construct exhibited enhanced radiolysis, presumably due to direct radiation damage from α particles. Concurrently, AA was not able to preserve fluorescence of the dual-modality molecule labeled with 213Bi. Our findings have important consequences for several research areas including ROS sensing, radiation-mediated drug release (uncaging), fluorescent dosimetry, and in the preparation of dual-modality radiopharmaceuticals. PMID:28042311

  17. 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.

  18. 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

  19. Influence of voxel S factors on three-dimensional internal dosimetry calculations.

    PubMed

    Berenato, Salvatore; Amato, Ernesto; Fischer, Alexander; Baldari, Sergio

    2016-10-01

    Internal dosimetry is a fundamental instrument for the personalization of nuclear medicine therapies, to maximize the therapeutic effect while minimizing the radiation burden to other organs. Three-dimensional (3D) dosimetry can quantify the impact of heterogeneous radiopharmaceutical distributions in organs, lesions and tissues. We analysed the influence of radionuclide voxel S factors in 3D dosimetry of (111)In, (177)Lu and (90)Y, the most used radionuclides in Peptide Receptor Radionuclide Therapy (PRRT). Calculations were carried out for kidneys on a workstation equipped with a software for 3D dosimetry (Imalytics STRATOS, Philips AG), adopting a computational anthropomorphic phantom and, retrospectively, the SPECT-CT image series of a clinical case of PRRT. Two sets of voxel S factors were adopted: the pre-loaded Philips kernels, calculated by direct Monte Carlo simulation, and the ones calculated through a previously proposed analytical approach. Philips (111)In kernel did not account for mono-energetic Auger or Conversion electrons. Results indicate a difference of about -32% in voxel S factors for (111)In in 4.42mm voxel size and around -35% in 4.80mm voxel size, particularly self-dose values; this lead to significant shift in dose histograms and average doses. For (177)Lu and (90)Y, differences are about 2% and 12% for 4.42mm voxels and about -8% and 9% for 4.80mm voxels, respectively, attributable to the different calculation methods of the voxel S factors; this does not lead to significant discrepancies between the two dose histograms. Consequently, voxel S factors must account accurately for all radiations emitted by the nuclide.

  20. The influence of a thoria dispersion on preferred orientation in nickel alloys.

    NASA Technical Reports Server (NTRS)

    Hutchinson, W. B.; Wilcox, B. A.

    1973-01-01

    Preferred orientation has been examined in extruded, drawn, and swaged nickel, nickel-20% chromium, and nickel-20% chromium-10% tungsten, with and without a dispersion of 2 vol % of thoria particles. Duplex 100 (in carets) + 111 (in carets) fiber textures were observed in most cases. The 100 (in carets) component was stabilized by the presence of particles and also by the application of intermediate anneals during deformation. These results and the stability of the deformed state in thoriated nickel are attributed largely to the action of the particles in generating homogeneous deformation.

  1. 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.

  2. 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.

  3. Labeled cells in the investigation of hematologic disorders

    SciTech Connect

    Alavi, J.B.; Hansell, J.

    1984-07-01

    Radiolabeling techniques for white cells, platelets, and erythrocytes are reviewed. The early studies using diisopropylfluoro-32P contributed to an understanding of the production and circulation of the blood elements, and 51Cr proved useful in localizing sites of cell migration or destruction. 111In-oxine has further improved the understanding of blood cell organ sequestration, and permitted combined kinetic and organ imaging studies. Radionuclide labels have been essential for the elucidation of various hematologic disorders, such as the neutropenias, thrombocytopenias, anemias, and polycythemia. Many new treatments, including monoclonal antibodies, have been evaluated with radionuclides.

  4. Kinetic Theory for Electrodic Phase Transitions: The Voltammogram

    DTIC Science & Technology

    1994-05-04

    In section 3 we include diffusion and mass transport. In section 4 we apply our theory to the underpotential deposition of Cu onto Au(l11), and we give...not be discussed here as such. However, in the example of the underpotential deposition of Cu onto Au(111) in the presence of sulphuric acid as... deposition (UPD) of Cu onto Au(1ll) in the presence of sulphuric acid. As is known [22, 23] the voltammogram shows two distinct peaks, which do not appear

  5. Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors.

    PubMed

    Zhang, Hanwen; Chen, Jianhua; Waldherr, Christian; Hinni, Karin; Waser, Beatrice; Reubi, Jean Claude; Maecke, Helmut R

    2004-09-15

    Bombesin receptors are overexpressed on a variety of human tumors like prostate, breast, and lung cancer. The aim of this study was to develop radiolabeled (Indium-111, Lutetium-177, and Yttrium-90) bombesin analogues with affinity to the three bombesin receptor subtypes for targeted radiotherapy. The following structures were synthesized: diethylenetriaminepentaacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH1) and 1,4,7,10-tetraazacyclododecane-N,N',N",N"' -tetraacetic acid-gamma-aminobutyric acid-[D-Tyr6, beta-Ala11, Thi13, Nle14] bombesin (6-14) (BZH2). [111In]-BZH1 and in particular [90Y]-BZH2 were shown to have high affinity to all three human bombesin receptor subtypes with binding affinities in the nanomolar range. In human serum metabolic cleavage was found between beta-Ala11 and His12 with an approximate half-life of 2 hours. The metabolic breakdown was inhibited by EDTA and beta-Ala11-His12 (carnosine) indicating that carnosinase is the active enzyme. Both 111In-labeled peptides were shown to internalize into gastrin-releasing peptide-receptor-positive AR4-2J and PC-3 cells with similar high rates, which were independent of the radiometal. The biodistribution studies of [111In]-BZH1 and [111In]-BZH2 ([177Lu]-BZH2) in AR4-2J tumor-bearing rats showed specific and high uptake in gastrin-releasing peptide-receptor-positive organs and in the AR4-2J tumor. A fast clearance from blood and all of the nontarget organs except the kidneys was found. These radiopeptides were composed of the first pan-bombesin radioligands, which show great promise for the early diagnosis of tumors bearing not only gastrin-releasing peptide-receptors but also the other two bombesin receptor subtypes and may be of use in targeted radiotherapy of these tumors.

  6. Molecular-beam epitaxy of CrSi2 on Si(111)

    NASA Technical Reports Server (NTRS)

    Fathauer, R. W.; Grunthaner, P. J.; Lin, T. L.; Chang, K. T.; Mazur, J. H.

    1988-01-01

    The growth of CrSi2 on Si(111) in a commercial MBE system with a base pressure in the low 10 to the -11th torr range is reported. CrSi2 layers grown on Si(111) exhibit a strong tendency to form islands. Two particular epitaxial relationships are identified. Thick (210 nm) layers have been grown by four different techniques, with best results obtained by codepositing Cr and Si at elevated temperature. The grain size is observed to increase with substrate temperature, reaching 1-2 microns in a layer deposited at 825 C.

  7. Surface chemistry of polyimide precursors on Cu(111)

    NASA Astrophysics Data System (ADS)

    Ivanecky, J. E.; Child, C. M.; Campion, Alan

    1995-03-01

    We have investigated the bonding of the monomers pyromellitic dianhydride (PMDA) and oxydianiline (ODA) as well as model compounds, succinic anhydride, phthalic anhydride, and benzoic acid, on Cu(111) in ultrahigh vacuum. Unenhanced surface Raman spectroscopy was used to identify the adsorbed species. ODA was unreactive at 110 K; the surface vibrational features were identical to those in the condensed multilayer. In contrast, PMDA chemisorbed dissociatively to form a bidentate surface carboxylate. Succinic anhydride physisorbed at 110 K, whereas benzoic acid and phthalic anhydride both adsorbed dissociatively forming bridging surface carboxylates as was observed for PMDA. The surface Raman spectrum of PMDA showed resonance enhancement.

  8. Training Extract AFSC 51XX Computer Systems Officer AFPT 90-51X-468.

    DTIC Science & Technology

    1983-06-01

    C 1 55. ANALYZE PROGRAM DUMPS .93 N.M 2.2 M.6 .3ES ANALYZ SYSTEM DUMPS ,93 N.M 2.2 6 .0 - 499 MARE ENTRIES ON SYSTEM FAILURE LOGS ,97 l*O 11*1 IN.3...2.2 . 5.3 .0 " 657 APPROVE OR DISAPPROVE SYSTEM DOCUMENTATION SUCH AS BAIA .16 .C .2 .0 .0 REOUOQCMCMTS DOCUMENTS (RD? OR SYSTEM SPECIFICATIONS SSI 660...9.1 3,7 A 971 ASSISTI COMPUTER OPERATORS IN FAILURE RECOVERY PROCEDURES .91 75.7 10.1 21. 7.1 I I.1 518R4 MARE TDY APRANSEMENTS SUCH AS BILLETING

  9. 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.

  10. Imaging Prostate Cancer Microenvironment by Collagen Hybridization

    DTIC Science & Technology

    2015-10-01

    bearing a range of selected subcutaneous prostate cancer xenografts resulted in the observation of a trend in which CMP-800 accumulates with higher...xenogratfs to reflect androgen receptor sensitivity status, expression of the biomarker PSMA and speed at which the tumors were growing. Mice bearing ...2. [111In](CXH-A)-(lys2)-DTPA-CMP9-(cys1)-IRDye800CW SPECT-CT at 3-6 h post-injection. Five mice, each bearing a single PC-3 PIP (higher Δ collagen

  11. (68)Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Meta-Analysis.

    PubMed

    Graham, Michael M; Gu, Xiaomei; Ginader, Timothy; Breheny, Patrick; Sunderland, John

    2017-03-09

    (68)Ga-DOTATOC, a somatostatin receptor targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision-making. This meta-analysis summarizes the efficacy of (68)Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. Methods: The major electronic medical databases were searched for relevant papers over the period from January 2001 until November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with (111)In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. Results: The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers, sensitivity 92%,) and specificity (7 papers, specificity 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers - change in management in 51%); and comparison with (111)In-octreotide (2 papers, sensitivity of DOTATOC on a per lesion basis was 100%,for (111)In-octreotide was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Conclusion:(68)Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging, restaging, and to assist in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients

  12. 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.

  13. 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.

  14. A high performance hybrid battery based on aluminum anode and LiFePO4 cathode

    DOE PAGES

    Sun, Xiao-Guang; Bi, Zhonghe; Liu, Hansan; ...

    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.

  15. Dipole forbidden vibrational modes for NO and CO on Cu observed in the far IR

    SciTech Connect

    Hirschmugl, C.J. |; Dumas, P.; Suhren, M.; Chabal, Y.J.; Hoffmann, F.M.; Williams, G.P.

    1993-11-01

    IRRAS spectra of NO/Cu(111) and ({radical}3 {times} {radical}3)R30{degrees} coverage of CO/Cu(111) in the range 3000--180 cm{sup {minus}1} show both the adsorbate internal modes and features assigned to the hindered rotational modes. These dipole-forbidden features are characterized by asymmetric (mostly negative) absorption lineshapes and are accompanied by a change in broadband absorption. The shape and intensity of this broadband absorption is well accounted for by a scattering model.

  16. 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

  17. 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.

  18. 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.

  19. A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors.

    PubMed

    Chatterjee, Samit; Lesniak, Wojciech G; Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Azad, Babak Behnam; Pomper, Martin G; Nimmagadda, Sridhar

    2016-03-01

    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.

  20. 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.

  1. 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.

  2. Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites

    PubMed Central

    Sadowski, Samira M.; Neychev, Vladimir; Millo, Corina; Shih, Joanna; Nilubol, Naris; Herscovitch, Peter; Pacak, Karel; Marx, Stephen J.

    2016-01-01

    Purpose Gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. 68Ga-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs. Patients and Methods One hundred thirty-one patients were enrolled in a prospective study of patients undergoing 68Ga-DOTATATE PET/CT, 111In-pentetreotide single-photon emission computed tomography (SPECT)/CT and multiphasic CT scan, and/or magnetic resonance imaging in a blinded fashion with comprehensive biochemical testing. The primary outcome measure was the detection of lesions by each imaging study. Results 68Ga-DOTATATE PET/CT imaging detected 95.1% of lesions (95% CI, 92.4% to 96.8%) with an average maximum standardized uptake value of 65.4 ± 47 (range, 6.9 to 244), anatomic imaging detected 45.3% of lesions (95% CI, 37.9% to 52.9%), and 111In-pentetreotide SPECT/CT detected 30.9% of lesions (95% CI, 25.0% to 37.5%), with a significant difference between imaging modalities (P < .001). In four of 14 patients (28.6%), 68Ga-DOTATATE PET/CT found a previously unknown primary tumor, and detected primary GEPNET, lymph node, and distant metastases correctly in 72 of 113 lesions (63.7%) when compared with histopathology, with 22.1% and 38.9% detected by using 111In-pentetreotide SPECT/CT and anatomic imaging, respectively. On the basis of findings with 68Ga-DOTATATE PET/CT, 43 of 131 patients (32.8%) had a change in management recommendation. In patients with carcinoid symptoms but negative biochemical testing, 68Ga-DOTATATE PET/CT detected lesions in 65.2% of patients, 40% of which were detected neither by anatomic imaging nor by 111In-pentetreotide SPECT/CT. Conclusion

  3. 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.

  4. Alloimmunization prevents the migration of transfused indium-111-labeled granulocytes to sites of infection

    SciTech Connect

    Dutcher, J.P.; Schiffer, C.A.; Johnston, G.S.; Papenburg, D.; Daly, P.A.; Aisner, J.; Wiernik, P.H.

    1983-08-01

    111In-labeled granulocytes were used to study the effects of histocompatibility factors on the migration of transfused granulocytes to infected sites. Fourteen alloimmunized and 20 nonalloimmunized patients received approximately 10(8) 111In-labeled granulocytes from ABO-compatible, non-HLA-matched donors, and scans were performed over known infected sites. All 14 alloimmunized patients had lymphocytotoxic antibody (LCTAb) and required HLA-matched platelet transfusions. Of the nonalloimmunized patients, 20/20 had positive scans at sites of infection. None of the 20 had LCTAb, 0/17 had a positive lymphocytotoxic crossmatch (LCTXM) with the donor, and 3/18 had a positive leukoagglutinin crossmatch (LAXM). Thus, histocompatibility testing was not found to be important in nonalloimmunized patients. In contrast, only 3/14 alloimmunized patients had positive scans at sites of infection (p . 0.00001 compared to nonalloimmunized patients). One of 3 had a positive LCTXM and 2/3 had a positive LAXM. Of the alloimmunized patients, 10/11 with negative scans had a positive LCTXM and 8/11 had a positive LAXM. Labeled granulocytes failed to reach sites of infection in 11/14 (78%) alloimmunized patients, demonstrating that histocompatibility factors can be of major importance in affecting the outcome of granulocyte transfusions. Granulocytes from random donors are unlikely to be effective in alloimmunized patients. The lack of an adequate crossmatching technique is a major problem limiting the ability to provide granulocyte transfusions for alloimmunized patients.

  5. Stability of Erythrocyte Ghosts: A γ -Ray Perturbed Angular Correlation Study

    NASA Astrophysics Data System (ADS)

    Kruse, Carol A.; Tin, George W.; Baldeschwieler, John D.

    1983-03-01

    The structural integrity of erythrocyte ghosts made by the preswell and slow-dialysis techniques has been studied in vitro by use of γ -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 quantities 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.

  6. 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.

  7. Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy.

    PubMed

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-21

    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.

  8. 17AAG-induced internalisation of HER2-specific Affibody molecules

    PubMed Central

    Göstring, Lovisa; Lindegren, Sture; Gedda, Lars

    2016-01-01

    The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled 211At-ABY-025 and radiometal-labelled 111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter 211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells. PMID:27698830

  9. Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model.

    PubMed

    Muselaers, Constantijn H J; Oosterwijk, Egbert; Bos, Desirée L; Oyen, Wim J G; Mulders, Peter F A; Boerman, Otto C

    2014-01-01

    A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT study in mice with intraperitoneally growing ccRCC lesions. Mice with intraperitoneal xenografts were injected with 1, 3, 10, 30, or 100 μg of G250 labeled with 10 MBq indium 111 (111In) to determine the optimal protein dose. The optimal protein dose determined with imaging and biodistribution studies was used in a subsequent RIT experiment in three groups of 10 mice with intraperitoneal SK-RC-52 tumors. One group received 13 MBq 177Lu-DOTA-G250, a control group received 13 MBq nonspecific 177Lu-MOPC21, and the second control group was not treated and received 20 MBq 111In-DOTA-G250. The optimal G250 protein dose to target ccRCC in this model was 10 μg G250. Treatment with 13 MBq 177Lu-DOTA-G250 was well tolerated and resulted in significantly prolonged median survival (139 days) compared to controls (49-53 days, p  =  .015), indicating that RIT has potential in this metastatic ccRCC model.

  10. Whole organ and islet of Langerhans dosimetry for calculation of absorbed doses resulting from imaging with radiolabeled exendin

    PubMed Central

    van der Kroon, Inge; Woliner-van der Weg, Wietske; Brom, Maarten; Joosten, Lieke; Frielink, Cathelijne; Konijnenberg, Mark W.; Visser, Eric P.; Gotthardt, Martin

    2017-01-01

    Radiolabeled exendin is used for non-invasive quantification of beta cells in the islets of Langerhans in vivo. High accumulation of radiolabeled exendin in the islets raised concerns about possible radiation-induced damage to these islets in man. In this work, islet absorbed doses resulting from exendin-imaging were calculated by combining whole organ dosimetry with small scale dosimetry for the islets. Our model contains the tissues with high accumulation of radiolabeled exendin: kidneys, pancreas and islets. As input for the model, data from a clinical study (radiolabeled exendin distribution in the human body) and from a preclinical study with Biobreeding Diabetes Prone (BBDP) rats (islet-to-exocrine uptake ratio, beta cell mass) were used. We simulated 111In-exendin and 68Ga-exendin absorbed doses in patients with differences in gender, islet size, beta cell mass and radiopharmaceutical uptake in the kidneys. In all simulated cases the islet absorbed dose was small, maximum 1.38 mGy for 68Ga and 66.0 mGy for 111In. The two sources mainly contributing to the islet absorbed dose are the kidneys (33–61%) and the islet self-dose (7.5–57%). In conclusion, all islet absorbed doses are low (<70 mGy), so even repeated imaging will hardly increase the risk on diabetes. PMID:28067253

  11. The acetabulum: A prospective study of three-phase bone and indium white blood cell scintigraphy following porous-coated hip arthroplasty

    SciTech Connect

    Oswald, S.G.; Van Nostrand, D.; Savory, C.G.; Anderson, J.H.; Callaghan, J.J. )

    1990-03-01

    Although few studies address the use of three-phase bone scanning (TPBS) and indium-111-labeled white blood cell scintigraphy ({sup 111}In-WBC) in hip arthroplasty utilizing a porous-coated prosthesis, the literature suggests that scintigraphic patterns in the uncomplicated patient may differ from that seen with the cemented prosthesis. In an attempt to determine the scintigraphic natural history, 25 uncomplicated porous-coated hip arthroplasties in 21 patients were prospectively studied with serial TPBS and {sup 111I}n-WBC at approximately 7 days, and 3, 6, 12, 18, and 24 mo postoperatively. This report deals with findings related to the acetabulum. All 25 prostheses (144 of 144 scans) demonstrated increased uptake on the bone-phase images. Although this activity decreased with time, 76% had persistent uptake at 24 mo. Twenty-three of 25 prostheses (126 of 140 scans) showed increased uptake on {sup 111}In-WBC scintigraphy, invariably decreasing with time, but with 37% having significant uptake at 24 mo. Scintigraphic patterns in the uncomplicated porous-coated hip arthroplasty patient appear to differ from patterns described in cemented prostheses.

  12. 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.

  13. Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging

    SciTech Connect

    Machac, J.; Vallabhajosula, S.; Goldman, M.E.; Goldsmith, S.J.; Palestro, C.; Strashun, A.; Vaquer, R.; Phillips, R.A.; Fuster, V. )

    1989-09-01

    Blood-pool subtraction has been proposed to enhance {sup 111}In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, blinded readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.

  14. 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.

  15. Assessment of myocardial damage in dilated-phase hypertrophic cardiomyopathy by using indium-111-antimyosin Fab myocardial scintigraphy

    SciTech Connect

    Nishimura, T.; Nagata, S.; Uehara, T.; Hayashida, K.; Mitani, I.; Kumita, S. )

    1991-07-01

    For the detection of myocardial cell damage, an 111In-antimyosin Fab study was carried out on seven patients (Group A) in the dilated phase of hypertrophic cardiomyopathy, seven patients (Group B) with dilated cardiomyopathy, and eight control patients (Group C). Imaging was done 48 hr after intravenous injection of 74 MBq of 111In-antimyosin Fab. Myocardial antimyosin uptake was visually graded as 0, +1, +2 or +3. A score of +2 or +3 was considered positive. The heart/lung ratio of antimyosin uptake (antimyosin index) also was determined. Antimyosin uptake was positive in seven (100%), nine (90%) and no (0%) patients in Groups A, B, and C, respectively. The antimyosin index in Groups A and B was 2.46 {plus minus} 0.49 and 2.04 {plus minus} 0.24, respectively, findings were significantly higher than that in Group C (1.51 {plus minus} 0.13) (p less than 0.01). Positive biopsy findings were noted in only two patients in Group A. Thus, antimyosin uptake was increased in dilated phase hypertrophic cardiomyopathy and dilated cardiomyopathy, which suggests ongoing necrotic changes in these patients.

  16. 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.

  17. A new approach to assessment and management of the impact from medical liquid radioactive waste.

    PubMed

    Sundell-Bergman, S; de la Cruz, I; Avila, R; Hasselblad, S

    2008-10-01

    The Swedish regulations concerning disposal of clinical radioactive waste are currently under revision and a graded approach is proposed for risk limitation purposes. To assist the revision procedures, a screening study was performed to estimate public exposures from liquid releases from hospitals to public sewers. The results showed that doses to sewage workers were above the dose constraint of 100 microSv a(-1) especially for 131I and (99m)Tc. Hence, a dynamic model, LUCIA, was developed for realistic assessments in which radionuclide transportation in sewers was modelled. Probabilistic simulations were performed to obtain probability distributions of radionuclide concentrations in sludge. Concurrently, estimates of the effective doses to sewage workers decreased significantly and were below 10 microSv a(-1) except for 111In and 131I. However, the Kd-coefficients representing the partition of radioactivity between water and sludge in sewers are highly uncertain for 111In. As shown by sensitivity studies, these values are the major determinant of the exposures in sewers.

  18. Tumor immunoscintigraphy by means of radiolabeled monoclonal antibodies: Multicenter studies of the Italian National Research Council--Special Project Biomedical Engineering

    SciTech Connect

    Siccardi, A.G. )

    1990-02-01

    Four radioimmunopharmaceuticals ({sup 99m}Tc- and 111In-labeled anti-melanoma and {sup 111}In- and {sup 131}I-labeled anti-carcinoembryonic antigen F(ab')2 fragments derived from monoclonal antibodies 225.28S and F023C5) were developed by means of a collaborative effort coordinated by the Italian National Research Council, Special Project Biomedical Engineering. After appropriate pilot studies, the radioimmunopharmaceuticals, prepared by Sorin Biomedica (Saluggia, Italy), were distributed to 31 Nuclear Medicine departments in Italy and in 10 other European countries within the framework of three immunoscintigraphy multicenter studies. A total of 1245 patients were studied, 898 of whom carried 1725 documented tumor lesions; 1596 of 2193 tumor lesions (468 of which were previously unknown) were imaged by immunoscintigraphy in 785 of 990 lesion-bearing patients. Among the occult lesions, 173 were imaged in 92 patients admitted to the study as lesion-free patients. The results have been analyzed in terms of the reliability, reproducibility, and diagnostic usefulness of the method and of each immunoradiopharmaceutical.

  19. 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.

  20. 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.

  1. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

    SciTech Connect

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-11-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (/sup 111/In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated /sup 111/In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.

  2. Antitumor Activity of VB-111, a Novel Antiangiogenic Virotherapeutic, in Thyroid Cancer Xenograft Mouse Models

    PubMed Central

    Reddi, H. V.; Madde, P.; Cohen, Y. C.; Bangio, L.; Breitbart, E.; Harats, D.; Bible, K. C.

    2011-01-01

    VB-111 is an engineered antiangiogenic adenovirus that expresses Fas-c in angiogenic blood vessels and has previously been shown to have significant antitumor activity in vitro and in vivo in Lewis lung carcinoma, melanoma, and glioblastoma models. To evaluate the efficacy of VB-111 in thyroid cancer, we conducted in vivo xenograft nude mouse studies using multiple thyroid cancer-derived cell lines models. VB-111 treatment resulted in 26.6% (P = 0.0596), 34.4% (P = 0.0046), and 37.6% (P = 0.0249) inhibition of tumor growth in follicular, papillary and anaplastic thyroid cancer models, respectively. No toxicity was observed in any model. All tumor types showed a consistent and significant reduction of CD-31 staining (P < 0.05), reflecting a reduction of angiogenic activity in the tumors, consistent with the intended targeting of the virus. A phase 2 clinical trial of VB-111 in patients with advanced differentiated thyroid cancer is ongoing. PMID:22701765

  3. Nuclear imaging of amyloidosis.

    PubMed

    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. (123)I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. (99m)Tc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as (201)Tl, (123)I-mIBG, together with (111)In-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. (67)Ga-citrate and (99m)Tc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with (131)I or (111)In. Among PET tracers, (11)C-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.

  4. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    PubMed

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  5. Investigation of hyperfine interactions in GdCrO3 perovskite oxide using PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Silva, Renilson A. Da; Saxena, R. N.; Carbonari, A. W.; Cabrera-Pasca, G. A.

    2010-04-01

    Perturbed angular correlation (PAC) measurements have been carried out in the antiferromagnetic GdCrO3 perovskite oxide using 111In (111Cd) and 181Hf(181Ta) nuclear probes. The radioactive parent nuclei 111In and 181Hf were introduced in the compound through a chemical process during sample preparation. The PAC measurements were carried out in the temperature range 20-300 K. Measurements with the 181Ta indicated a unique quadrupole interaction above 170 K and a combined electric quadrupole and magnetic dipole interactions below this temperature. The observed interaction was assigned to the probe nuclei substituting Cr sites. Measurements with 111Cd showed two quadrupole interactions. Only one of the fractions however, showed a combined electric and magnetic interaction in the temperature rage 20-170 K which was assigned to 111Cd probe substituting Cr site. The other fraction was attributed to the Gd site. The present results are compared with those of LaCrO3 and NdCrO3.

  6. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  7. In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis

    SciTech Connect

    Read, E.J.; Keenan, A.M.; Carter, C.S.; Yolles, P.S.; Davey, R.J. )

    1990-06-01

    The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with {sup 111}In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) {sup 111}In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skin test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.

  8. 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.

  9. Enthalpy-Entropy Tuning in the Adsorption of Nucleobases at the Au(111) Surface.

    PubMed

    Rosa, Marta; Corni, Stefano; Di Felice, Rosa

    2014-04-08

    The interaction of DNA molecules with hard substrates is of paramount importance both for the study of DNA itself and for the variety of possible technological applications. Interaction with inorganic surfaces strongly modifies the helical shape of DNA. Hence, an accurate understanding of DNA structure and function at interfaces is a fundamental question with enormous impact in science and society. This work sets the fundamentals for the simulation of entire DNA oligomers on gold surfaces in dry and wet conditions. Thanks to the new GolDNA-AMBER force field, which was derived from first principles and includes dispersion interactions and polarization effects, we simulated self-assembled guanine and adenine monolayers on Au(111) in vacuo and the adsorption of all nucleobases on the same substrate in aqueous conditions. The periodic monolayers obtained from classical simulations match very well those from first principle calculations and experiments, assessing the robustness of the force field and motivating the application to more complex systems for which quantum calculations are not affordable and experiments are elusive. The energetics of nucleobases on Au(111) in solution reveal fundamental physicochemical effects: we find that the adsorption paradigm shifts from purely enthalpic to dominantly entropic by changing the environment and aggregation phase.

  10. 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 - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, 111In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of 111In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers. PMID:27080529

  11. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments.

    PubMed

    Eter, Wael A; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-04-15

    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 - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, (111)In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of (111)In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers.

  12. Development and preclinical studies of (64)Cu-NOTA-pertuzumab F(ab')2 for imaging changes in tumor HER2 expression associated with response to trastuzumab by PET/CT.

    PubMed

    Lam, Karen; Chan, Conrad; Reilly, Raymond M

    2017-01-01

    We previously reported that microSPECT/CT imaging with (111)In-labeled pertuzumab detected decreased HER2 expression in human breast cancer (BC) xenografts in athymic mice associated with response to treatment with trastuzumab (Herceptin). Our aim was to extend these results to PET/CT by constructing F(ab')2 of pertuzumab modified with NOTA chelators for complexing (64)Cu. The effect of the administered mass (5-200 µg) of (64)Cu-NOTA-pertuzumab F(ab')2 was studied in NOD/SCID mice engrafted with HER2-positive SK-OV-3 human ovarian cancer xenografts. Biodistribution studies were performed in non-tumor bearing Balb/c mice to predict radiation doses to normal organs in humans. Serial PET/CT imaging was conducted on mice engrafted with HER2-positive and trastuzumab-sensitive BT-474 or trastuzumab-insensitive SK-OV-3 xenografted mice treated with weekly doses of trastuzumab. There were no significant effects of the administered mass of (64)Cu-NOTA-pertuzumab F(ab')2 on tumor or normal tissue uptake. The predicted total body dose in humans was 0.015 mSv/MBq, a 3.3-fold reduction compared to (111)In-labeled pertuzumab. MicroPET/CT images revealed specific tumor uptake of (64)Cu-NOTA-pertuzumab F(ab')2 at 24 or 48 h post-injection in mice with SK-OV-3 tumors. Image analysis of mice treated with trastuzumab showed 2-fold reduced uptake of (64)Cu-NOTA-pertuzumab F(ab')2 in BT-474 tumors after 1 week of trastuzumab normalized to baseline, and 1.9-fold increased uptake in SK-OV-3 tumors after 3 weeks of trastuzumab, consistent with tumor response and resistance, respectively. We conclude that PET/CT imaging with (64)Cu-NOTA-pertuzumab F(ab')2 detected changes in HER2 expression in response to trastuzumab while delivering a lower total body radiation dose compared to (111)In-labeled pertuzumab.

  13. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy

    SciTech Connect

    Baechler, Sebastien; Hobbs, Robert F.; Boubaker, Ariane; Buchegger, Franz; He Bin; Frey, Eric C.; Sgouros, George

    2012-10-15

    Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with {sup 111}In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., {sup 111}In, {sup 90}Y and {sup 177}Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for {sup 90}Y and {sup 177}Lu. Nevertheless, for {sup 111}In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated

  14. NanoFerrite particle based radioimmunonanoparticles: binding affinity and in vivo pharmacokinetics.

    PubMed

    Natarajan, A; Gruettner, C; Ivkov, R; DeNardo, G L; Mirick, G; Yuan, A; Foreman, A; DeNardo, S J

    2008-06-01

    Dextran and PEG-coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal antibodies, scFv, and peptides conjugated to 20 nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NPs can affect their in vivo performance. Surface morphology, surface charge density, and particle size are considered important factors that determine pharmacokinetics, toxicity, and biodistribution. New NanoFerrite (NF) particles having improved specific AMF absorption rates and diameters of 30 and 100 nm were studied to evaluate the variation in their in vitro and in vivo characteristics in comparison to the previously studied 20 nm superparamagnetic iron oxide (SPIO) NP. SPIO NP 20 nm and NF NP 30 and 100 nm were conjugated to (111)In-DOTA-ChL6, a radioimmunoconjugate. Radioimmunoconjugates were conjugated to NPs using 25 microg of RIC/mg of NP by carbodiimide chemistry. The radioimmunonanoparticles (RINP) were purified and characterized by PAGE, cellulose acetate electrophoresis (CAE), live cell binding assays, and pharmacokinetics in athymic mice bearing human breast cancer (HBT 3477) xenografts. RINP (2.2 mg) were injected iv and whole body; blood and tissue data were collected at 4, 24, and 48 h. The preparations used for animal study were >90% monomeric by PAGE and CAE. The immunoreactivity of the RINP was 40-60% compared to (111)In-ChL6. Specific activities of the doses were 20-25 microCi/2.2 mg and 6-11 microg of mAb/2.2 mg of NP. Mean tumor uptakes (% ID/g +/- SD) of each SPIO 20 nm, NF 30 nm, and 100 nm RINP at 48 h were 9.00 +/- 0.8 (20 nm), 3.0 +/- 0.3 (30 nm), and 4.5 +/- 0.8 (100 nm), respectively; the ranges of tissue uptakes were liver (16-32 +/- 1-8), kidney (7.0-15 +/- 1), spleen (8-17 +/- 3-8), lymph nodes 5-6 +/- 1-2), and lung (2.0-4 +/- 0.1-2). In conclusion, this study

  15. What a Difference a Carbon Makes: H4octapa vs H4C3octapa, Ligands for In-111 and Lu-177 Radiochemistry

    PubMed Central

    2015-01-01

    The acyclic ligands H4C3octapa and p-SCN-Bn-H4C3octapa were synthesized for the first time, using nosyl protection chemistry. These new ligands were compared to the previously studied ligands H4octapa and p-SCN-Bn-H4octapa to determine the extent to which the addition of a single carbon atom to the backbone of the ligand would affect metal coordination, complex stability, and, ultimately, utility for in vivo radiopharmaceutical applications. Although only a single carbon atom was added to H4C3octapa and the metal donor atoms and denticity were not changed, the solution chemistry and radiochemistry properties were drastically altered, highlighting the importance of careful ligand design and radiometal–ligand matching. It was found that [In(C3octapa)]− and [Lu(C3octapa)]− were substantially different from the analogous H4octapa complexes, exhibiting fluxional isomerization and a higher number of isomers, as observed by 1H NMR, VT-NMR, and 2D COSY/HSQC-NMR experiments. Past evaluation of the DFT structures of [In(octapa)]− and [Lu(octapa)]− revealed very symmetric complexes; in contrast, the [In(C3octapa)]− and [Lu(C3octapa)]− complexes were much less symmetric, suggesting lower symmetry and less rigidity than that of the analogous H4octapa complexes. Potentiometric titrations revealed the formation constants (log KML, pM) were ∼2 units lower for the In3+ and Lu3+ complexes of H4C3octapa when compared to that of the more favorable H4octapa ligand (∼2 orders of magnitude less thermodynamically stable). The bifunctional ligands p-SCN-Bn-H4C3octapa and p-SCN-Bn-H4octapa were conjugated to the antibody trastuzumab and radiolabeled with 111In and 177Lu. Over a 5 day stability challenge experiment in blood serum, 111In-octapa– and 111In-C3octapa–trastuzumab immunoconjugates were determined to be ∼91 and ∼24% stable, respectively, and 177Lu-octapa– and 177Lu-C3octapa–trastuzumab, ∼89% and ∼4% stable, respectively. This work suggests that 5

  16. NanoFerrite Particle Based Radioimmunonanoparticles: Binding affinity and in vivo pharmacokinetics

    PubMed Central

    Natarajan, A.; Gruettner, C.; Ivkov, R.; DeNardo, G. L.; Mirick, G.; Yuan, A.; Foreman, A.; DeNardo, S. J.

    2008-01-01

    Dextran and PEG coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal Antibodies, scFv, and peptides conjugated to 20-nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NP's can affect their in vivo performance. Surface morphology, surface charge density, and particle size are considered important factors that determine pharmacokinetics, toxicity, and biodistribution. New NanoFerrite (NF) particles having improved specific AMF absorption rates and diameters of 30 nm and 100 nm were studied to evaluate the variation in their in vitro and in vivo characteristics in comparison to the previously studied 20 nm Superparamagnetic Iron Oxide (SPIO) NP. SPIO NP 20-nm, NF NP 30- and 100-nm were conjugated to 111In-DOTA-ChL6, a radioimmunoconjugate. Radioimmunoconjugates were conjugated to NP's using 25μg of RIC/mg of NP by carbodiimide chemistry. The radioimmunonanoparticles (RINP) were purified characterized by PAGE, cellulose acetate electrophoresis (CAE), live cell binding assays, and pharmacokinetics in athymic mice bearing human breast cancer (HBT 3477) xenografts. RINP (2.2 mg) were injected iv and whole body, blood and tissue data were collected at 4, 24, and 48 hours. The preparations used for animal study were >90% monomeric by PAGE and CAE. The immunoreactivity of the RINP was 40−60% compared to 111In-ChL6. Specific activities of the doses were 20−25μCi/2.2 mg and 6−11μg of MAb/2.2 mg of NP. Mean tumor uptakes (% ID/g ± SD) of each SPIO 20nm, NF 30nm, and 100nm RINP at 48h were 9.00 ± 0.8 (20nm), 3.0 ± 0.3 (30nm), and 4.5 ± 0.8 (100nm) respectively; the ranges of tissue uptakes were liver (16−32 ± 1 − 8), kidney (7.0−15 ± 1) spleen (8−17 ± 3 − 8) lymph nodes 5 − 6 ± 1 −2) and lung (2.0− 4 ± 0.1 − 2). In conclusion, this study

  17. A 90Y-labelled anti-ROBO1 monoclonal antibody exhibits antitumour activity against hepatocellular carcinoma xenografts during ROBO1-targeted radioimmunotherapy

    PubMed Central

    2014-01-01

    Background ROBO1 is a membrane protein that functions in axon guidance. ROBO1 contributes to tumour metastasis and angiogenesis and may have potential as a target protein of immunotherapy because ROBO1 is specifically expressed at high levels in hepatocellular carcinoma. In this study, we examined biodistribution and radioimmunotherapy (RIT) using a radioisotope-labelled anti-ROBO1 monoclonal antibody (MAb) against hepatocellular carcinoma models. Methods ROBO1-positive HepG2 human hepatocellular carcinoma xenograft nude mice were used in this study. We conjugated anti-ROBO1 MAb with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and the conjugates were labelled with 111In and 90Y. To study biodistribution, the 111In-DOTA-anti-ROBO1 MAb was injected into HepG2 xenograft mice via the tail vein. To evaluate any antitumour effect, a RIT study was performed, and the 90Y-DOTA-anti-ROBO1 MAb was injected via the tail vein. Tumour volume, mouse weight, and blood cell count were periodically measured throughout the experiments. The tumours and organs of mice were collected, and a histopathological analysis was carried out. Results The tumour uptake of 111In-anti-ROBO1 MAb in HepG2 xenograft mice was 15.0% ± 0.69% injected dose per gram at 48 h after injection. Immunotherapy with cold-anti-ROBO1 MAb (70 μg) did not cause a significant antitumour effect. RIT with 6.7 MBq of 90Y-anti-ROBO1 MAb caused significant tumour growth suppression. Transient body weight loss and bone-marrow suppression were observed. Histopathological analyses of tumours revealed the fatal degeneration of tumour cells, significant reduction of the Ki-67 index, and an increase of the apoptosis index. Normal organs showed no significant injury, but a transient reduction of hematopoietic cells was observed in the spleen and in the sternal bone marrow. Conclusions These results suggest that RIT with 90Y-anti-ROBO1 MAb is a promising treatment for ROBO1-positive hepatocellular

  18. Effect of radiochemical modification on biodistribution of scFvD2B antibody fragment recognising prostate specific membrane antigen.

    PubMed

    Frigerio, Barbara; Benigni, Fabio; Luison, Elena; Seregni, Ettore; Pascali, Claudio; Fracasso, Giulio; Morlino, Sara; Valdagni, Riccardo; Mezzanzanica, Delia; Canevari, Silvana; Figini, Mariangela

    2015-11-01

    Antibody-based reagents represent a promising strategy as clinical diagnostic tools. Prostate cancer (PCa) is the second-leading cause of death in males in the Western population. There is a presently unmet need for accurate diagnostic tool to localize and define the extent of both primary PCa and occult recurrent disease. One of the most suitable targets for PCa is the prostate-specific membrane antigen (PSMA) recognised by the monoclonal antibody D2B that we re-shaped into the single chain Fv (scFv format). Aim of this study was to evaluate in preclinical in vivo models the target specificity of scFvD2B after labelling with different radionuclides. (111)In radiolabelling was performed via the chelator Bz-NOTA, and (131)I radioiodination was performed using iodogen. The potential for molecular imaging and the biological behaviour of the radiolabelled scFvD2B were evaluated in mice bearing two subcutaneous PCa isogenic cell lines that differed only in PSMA expression. Biodistribution studies were performed at 3, 9, 15 and 24h after injection to determine the optimal imaging time point. A significant kidney accumulation, as percentage of injected dose of tissue (%ID/g), was observed for (111)In-scFvD2B at 3h after injection (45%ID/g) and it was maintained up to 24h (26%ID/g). By contrast, kidney accumulation of (131)I-scFvD2B was only marginally (0.3%ID/g at 24h). At the optimal time point defined between 15h and 24h, regardless of the radionuclide used, the scFvD2B was able to localize significantly better in the PSMA expressing tumours compared to the negative control; with (131)I-scFvD2B yielding a significantly better target/background ratio compared to (111)In-scFvD2B. These data suggest that, besides antigen specificity, chemical modification may affect antibody fragment biodistribution.

  19. Targeted actinium-225 in vivo generators for therapy of ovarian cancer.

    PubMed

    Borchardt, Paul E; Yuan, Rui R; Miederer, Matthias; McDevitt, Michael R; Scheinberg, David A

    2003-08-15

    Advanced ovarian cancer is largely incurable, but initially it is frequently confined to the i.p. space. We explored i.p. radioimmunotherapy in a mouse model of human ovarian cancer. Use of a targeted actinium-225 ((225)Ac) in vivo generator of alpha particles exploits the extreme, selective cytotoxicity of alpha particles, while providing a feasible half-life to enable delivery to tumor. (225)Ac chelated with 2-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraacetic acid was conjugated to trastuzumab, an anti-HER-2/neu antibody. The radioimmunoconjugate was tested for immunoreactivity, internalization, and cytotoxicity using a human ovarian carcinoma cell line, SKOV3. (225)Ac-labeled trastuzumab retained immunoreactivity (50-90%), rapidly internalized into cells (50% at 2 h), and had an ED(50) of 1.3 nCi/ml after 4 days of incubation in vitro. i.p. administered (225)Ac- or (111)In-labeled trastuzumab behaved similarly with high tumor uptake [56-60% injected dose per gram (% ID/g) at 4 h, which increased to 65-70% ID/g at 24 h]. Tumor uptake was 3-5-fold higher than liver and spleen, the normal organs with the highest uptake. i.v. administration of (111)In-labeled trastuzumab produced slightly higher normal organ uptake compared with i.p.-administered (111)In-labeled trastuzumab. However, tumor uptake was low, 5%-26% ID/g. Therapy was examined with native trastuzumab and 220, 330, and 450 nCi of (225)Ac-labeled trastuzumab or (225)Ac-labeled control antibody at different dosing schedules. Therapy was initiated 9 days after tumor seeding. Groups of control mice and those administered native trastuzumab had median survivals of 33 and 37 or 44 days, respectively. Median survival was 52-126 days with (225)Ac-labeled trastuzumab at various doses and schedules, and 48-64 days for (225)Ac-labeled control the same schedules. Deaths from toxicity occurred with the highest activity levels. In conclusion, i.p. administration with a (225)Ac

  20. Evaluation of quantitative accuracy in CZT-based pre-clinical SPECT for various isotopes

    NASA Astrophysics Data System (ADS)

    Park, S.-J.; Yu, A. R.; Kim, Y.-s.; Kang, W.-S.; Jin, S. S.; Kim, J.-S.; Son, T. J.; Kim, H.-J.

    2015-05-01

    In vivo pre-clinical single-photon emission computed tomography (SPECT) is a valuable tool for functional small animal imaging, but several physical factors, such as scatter radiation, limit the quantitative accuracy of conventional scintillation crystal-based SPECT. Semiconductor detectors such as CZT overcome these deficiencies through superior energy resolution. To our knowledge, little scientific information exists regarding the accuracy of quantitative analysis in CZT-based pre-clinical SPECT systems for different isotopes. The aim of this study was to assess the quantitative accuracy of CZT-based pre-clinical SPECT for four isotopes: 201Tl, 99mTc, 123I, and 111In. The quantitative accuracy of the CZT-based Triumph X-SPECT (Gamma-Medica Ideas, Northridge, CA, U.S.A.) was compared with that of a conventional SPECT using GATE simulation. Quantitative errors due to the attenuation and scatter effects were evaluated for all four isotopes with energy windows of 5%, 10%, and 20%. A spherical source containing the isotope was placed at the center of the air-or-water-filled mouse-sized cylinder phantom. The CZT-based pre-clinical SPECT was more accurate than the conventional SPECT. For example, in the conventional SPECT with an energy window of 10%, scatter effects degraded quantitative accuracy by up to 11.52%, 5.10%, 2.88%, and 1.84% for 201Tl, 99mTc, 123I, and 111In, respectively. However, with the CZT-based pre-clinical SPECT, the degradations were only 9.67%, 5.45%, 2.36%, and 1.24% for 201Tl, 99mTc, 123I, and 111In, respectively. As the energy window was increased, the quantitative errors increased in both SPECT systems. Additionally, the isotopes with lower energy of photon emissions had greater quantitative error. Our results demonstrated that the CZT-based pre-clinical SPECT had lower overall quantitative errors due to reduced scatter and high detection efficiency. Furthermore, the results of this systematic assessment quantifying the accuracy of these SPECT

  1. Interactions between chromosomal omnipotent suppressors and extrachromosomal effectors in Saccharomyces cerevisiae.

    PubMed

    Ono, B; Chernoff, Y O; Ishino-Arao, Y; Yamagishi, N; Shinoda, S; Inge-Vechtomov, S G

    1991-04-01

    Chromosomal omnipotent suppressor mutations recovered in psi+ strains of Saccharomyces cerevisiae were brought into psi- cytoplasm. SUP46, SUP138 and SUP139 acted as dominant omnipotent suppressors in the psi- cytoplasm though their suppressor activity was substantially reduced. SUP46 and SUP138 conferred recessive thermosensitivity and antibiotic sensitivity in psi- cytoplasm as in psi+ cytoplasm. On the other hand, sup111 through sup115, which acted as recessive omnipotent suppressors in the psi+ cytoplasm, manifested no, or very low, suppressor activity in the psi- cytoplasm. They, however, still enhanced the efficiency of the SUP29 tRNA suppressor in psi- cytoplasm. A multicopy plasmid carrying the wild-type SUP35 gene enhanced the efficiency of sup111 in psi- cytoplasm.

  2. [Study of the circulation of Crimean hemorrhagic fever virus in Turkmenistan].

    PubMed

    Smirnova, S E; Mamaev, V I; Nepesova, N M; Filipenko, P I; Kalieva, V Ia

    1978-01-01

    Final results of the virological and serological investigations of the circulation of the Crimean hemorrhagic fever virus in the Turkmenian SSR carried out in 1968-1976 are presented in this report. In the examination of 2294 blood serum samples of human beings complement binding antibodies against the Crimean hemorrhagic fever were revealed in 0.4% of cases. It was revealed that five species of ixodes ticks could he infected with this virus; for the first time its strains were also isolated from the Hyalomma dromedarii ticks. Isolation of the Crimean hemorrhagic fever virus from ticks and determination of the precipitating antibodies against this virus in agricultural animals--from 6.2 to 11.1%--in all the regions of the republic pointed out that the natural nidi zones were widespread at the territory of the Turkmenian SSR, and that it was necessary to carry out further study of the given focus.

  3. Solvent-assisted growth of metal phthalocyanine thin films on Au(111)

    SciTech Connect

    Tskipuri, Levan; Shao Qian; Reutt-Robey, Janice

    2012-05-15

    Thin films of metal phthalocyanine (MPc) are grown on an Au(111) support with a newly developed aerosol molecular beam deposition source and characterized in situ via ultrahigh vacuum scanning tunneling microscopy. MPcs are delivered to Au(111) in a series of N{sub 2}-entrained microsized solvent droplets of variable surface residence time. Phthalocyanine film registration to the herringbone reconstruction of the Au(111) surface, indicative of thermodynamically favored structure, is observed at submonolayer coverages for aromatic solvents with long residence times. Aerosol-deposited monolayer film structures are noncrystalline with tilted MPc orientations and vacancy nanocavities. Upon annealing, MPc molecules adopt flat-lying orientations with respect to the substrate and vacancies are eliminated. Film morphologies indicate solvation-mediated film nucleation and growth, with less long-range ordering that in vapor-generated films.

  4. Spinal dural enhancement on magnetic resonance imaging associated with spontaneous intracranial hypotension. Report of three cases and review of the literature.

    PubMed

    Moayeri, N N; Henson, J W; Schaefer, P W; Zervas, N T

    1998-05-01

    This report offers a description of typical changes seen on gadolinium-enhanced magnetic resonance (MR) imaging of the entire spine that indicate spontaneous intracranial hypotension (SIH). To the authors' knowledge, this is the first report of its kind. They describe three cases of SIH that were accompanied by dural enhancement throughout the neuraxis on imaging, with the evolution of associated subdural and epidural fluid collections in the spine. Recognition of this disorder is important to be able to distinguish it from an infectious or neoplastic process in which surgical intervention might be warranted. Evaluation using gadolinium-enhanced cranial and spinal MR imaging in patients with postural headaches and an (111)In-labeled cerebrospinal fluid leak study are discussed. Treatment with an epidural blood patch is shown to be particularly effective, with resolution of the radiological and clinical findings.

  5. Improved control over spontaneously formed GaN nanowires in molecular beam epitaxy using a two-step growth process.

    PubMed

    Zettler, J K; Corfdir, P; Geelhaar, L; Riechert, H; Brandt, O; Fernández-Garrido, S

    2015-11-06

    We investigate the influence of modified growth conditions during the spontaneous formation of GaN nanowires (NWs) on Si(111) in plasma-assisted molecular beam epitaxy. We find that a two-step growth approach, where the substrate temperature is increased during the nucleation stage, is an efficient method to gain control over the area coverage, average diameter, and coalescence degree of GaN NW ensembles. Furthermore, we also demonstrate that the growth conditions employed during the incubation time that precedes nanowire nucleation do not influence the properties of the final nanowire ensemble. Therefore, when growing GaN NWs at elevated temperatures or with low Ga/N ratios, the total growth time can be reduced significantly by using more favorable growth conditions for nanowire nucleation during the incubation time.

  6. Radiolabeled peptides in oncology: role in diagnosis and treatment.

    PubMed

    Weiner, Ronald E; Thakur, Mathew L

    2005-01-01

    There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in the last decade. The automated means of synthesizing these compounds in large quantities and the simplified methods of purifying, characterizing, and optimizing them have kindled attention to peptides as carrier molecules. These new techniques have accelerated the commercial development of radiolabelled peptides, which has provided additional radiopharmaceuticals for the nuclear medicine community. Peptides have many key properties including fast clearance, rapid tissue penetration, and low antigenicity, and can be produced easily and inexpensively. However, there may be problems with in vivo catabolism, unwanted physiologic effects, and chelate attachment. Radiolabeled peptides have made their greatest impact in the management of relatively rare neuroendocrine malignancies. Indeed, Indium-111 ((111)In)-pentetreotide ((111)In-DTPA-octreotide, Octreoscan), which binds to somatostatin receptors (SSTRs), has become the diagnostic 'gold standard' in these diseases. However, (111)In-pentetreotide has been less successful in the diagnosis of other more prevalent diseases in which SSTRs are upregulated. Technetium-99m (99mTc)-depreotide (NeoTect), a 99mTc-labeled SSTR-analog, could have wider impact since it has high sensitivity and specificity for lung cancer lesion detection. However, this impact may be minimized by the increased availability of positron emission tomography imaging with Fluorine-18 (18F)-flourodeoxyglucose, which has similar sensitivity and specificity for lesion identification in this disease, and is currently more widely used. The receptors for bombesin, alpha-melanocyte-stimulating hormone, neurotensin, and the integrin alpha(v)beta3, are under active investigation as targets for radiolabelled peptides, but are still in the pre-clinical stage. Compounds directed at the cholecystokinin-B/gastrin receptor have shown promising

  7. [Inpatient and partial hospitalization facilities for child and adolescent psychiatry in the unified Germany, 1991].

    PubMed

    Specht, F; Anton, S

    1992-12-01

    First results of the project "Surveys regarding the structure of psychiatric institutions for children and adolescents in the Federal Republic of Germany" are described. On July 1, 1991 there were 111 in-patient institutions with a total capacity for 6363 children and youths. The contributing shares of each state (Bundesland) vary enormously. The number of accommodations per 100,000 residents is between 2.1 and 19. One reason for this discrepancy lies in the fact that the services of the institutions are called upon without regard to the state borders. More important though is the fact that in the new states the psychiatric institutions for children and youths also treat young patients who are psychologically or mentally handicapped with neuropsychiatric complications to a greater extent than comparable institutions in the old states.

  8. Sum Frequency Generation Studies of Hydrogenation Reactions on Platinum Nanoparticles

    SciTech Connect

    Krier, James M.

    2013-08-31

    Sum Frequency Generation (SFG) vibrational spectroscopy is used to characterize intermediate species of hydrogenation reactions on the surface of platinum nanoparticle catalysts. In contrast to other spectroscopy techniques which operate in ultra-high vacuum or probe surface species after reaction, SFG collects information under normal conditions as the reaction is taking place. Several systems have been studied previously using SFG on single crystals, notably alkene hydrogenation on Pt(111). In this thesis, many aspects of SFG experiments on colloidal nanoparticles are explored for the first time. To address spectral interference by the capping agent (PVP), three procedures are proposed: UV cleaning, H2 induced disordering and calcination (core-shell nanoparticles). UV cleaning and calcination physically destroy organic capping while disordering reduces SFG signal through a reversible structural change by PVP.

  9. Direct mapping of spin and orbital entangled wave functions under interband spin-orbit coupling of giant Rashba spin-split surface states

    NASA Astrophysics Data System (ADS)

    Noguchi, Ryo; Kuroda, Kenta; Yaji, K.; Kobayashi, K.; Sakano, M.; Harasawa, A.; Kondo, Takeshi; Komori, F.; Shin, S.

    2017-01-01

    We use spin- and angle-resolved photoemission spectroscopy (SARPES) combined with a polarization-variable laser and investigate the spin-orbit coupling effect under interband hybridization of Rashba spin-split states for the surface alloys Bi/Ag(111) and Bi/Cu(111). In addition to the conventional band mapping of photoemission for Rashba spin splitting, the different orbital and spin parts of the surface wave function are directly imaged into energy-momentum space. It is unambiguously revealed that the interband spin-orbit coupling modifies the spin and orbital character of the Rashba surface states leading to the enriched spin-orbital entanglement and the pronounced momentum dependence of the spin polarization. The hybridization thus strongly deviates the spin and orbital characters from the standard Rashba model. The complex spin texture under interband spin-orbit hybridization proposed by first-principles calculation is experimentally unraveled by SARPES with a combination of p - and s -polarized light.

  10. Theranostic etoposide phosphate/indium nanoparticles for cancer therapy and imaging.

    PubMed

    Srinivas, Ramishetti; Satterlee, Andrew; Wang, Yuhua; Zhang, Yuan; Wang, Yongjun; Huang, Leaf

    2015-11-28

    Etoposide phosphate (EP), a water-soluble anticancer prodrug, is widely used for treatment of many cancers. After administration it is rapidly converted to etoposide, its parent compound, which exhibits anticancer activity. Difficulty in parenteral administration necessitates the development of a suitable nanoparticle delivery system for EP. Here we have used indium both as a carrier to deliver etoposide phosphate to tumor cells and as a SPECT imaging agent through incorporation of (111)In. Etoposide phosphate was successfully encapsulated together with indium in nanoparticles, and exhibited dose dependent cytotoxicity and induction of apoptosis in cultured H460 cancer cells via G2/M cell cycle arrest. In a mouse xenograft lung cancer model, etoposide phosphate/indium nanoparticles induce tumor cell apoptosis, leading to significant enhancement of tumor growth inhibition compared to the free drug.

  11. An improved method for echographic detection of left atrial enlargement

    NASA Technical Reports Server (NTRS)

    Brown, O. R.; Harrison, D. C.; Popp, R. L.

    1974-01-01

    Echographic dimensions of the aortic root and left atrium were compared in 170 patients in order to assess dilation of the left atrium with reference to the relatively nondistensible fibrous aortic root. In 50 patients without cause for left atrial or aortic enlargement, the ratio of left atrial/aortic root dimensions was 0.87 to 1.11. In 80 patients with known cause for left atrial enlargement, the left atrial/aortic root ratio was greater than or equal to 1.17. In 40 patients with isolated valve disease, dilation of both the aortic root and the left atrium resulted in a left atrial/aortic root dimension ratio less than 1.17 in some patients. Despite this consideration, the comparison of left atrial and aortic root dimension appears to be as specific as, and more sensitive than, previously proposed methods for the evaluation of left atrial enlargement.

  12. Real-time investigations of Pt(111) surface transformations in sulfuric acid solutions.

    PubMed

    Braunschweig, Björn; Mukherjee, Prabuddha; Dlott, Dana D; Wieckowski, Andrzej

    2010-10-13

    We present the first broadband sum-frequency generation (SFG) spectra of adlayers from sulfuric acid solutions on Pt(111) surfaces and reveal surface transformations of (bi)sulfate anions in unprecedented detail. SFG amplitudes, bandwidth, and electrochemical Stark tuning of (bi)sulfate vibrational bands centered at 1250-1290 cm(-1) strongly depend on the applied potential and are correlated with prominent voltammetric features. (Bi)sulfate adlayers on Pt(111) are important model systems for weak, specific adsorption of anions on catalytically active surfaces. Although the existence of surface transformations on Pt(111) in dilute H(2)SO(4) solutions has been established by previous studies, so far they have not been observed with surface vibrational spectroscopy. Our results confirm previous reports of a surface transformation at 0.21 V and provide new information on a second transformation at 0.5 V due to surface hydroxyl formation and rearrangement of the electric double layer.

  13. Heteroepitaxial growth of a zeolite film with a patterned surface-texture.

    PubMed

    Wakihara, Toru; Yamakita, Shigehiro; Iezumi, Kumiko; Okubo, Tatsuya

    2003-10-15

    We focus on the eteroepitaxial growth of trigonal chabazite with voids of three-dimensional intersection structures. The differences in the structures originate from the stacking sequences of the six-membered rings. Sodalite along 111 is constructed by an "abcabc" stacking sequence, while chabazite along [111] is constructed by "abab". Therefore, chabazite can grow heteroepitaxially on a sodalite substrate while keeping the relation of chabazite (111)//sodalite {111}. In this Communication, we report on the first success of the heteroepitaxial growth of a continuous zeolite (chabazite) film with a unique patterned surface-texture on a millimeter-sized sodalite single crystal. We have found that the unique texture of chabazite films is rationalized by the heteroepitaxial growth of chabazite on sodalite and the subsequent twin formation of chabazite.

  14. Octreotide Uptake in Parathyroid Adenoma

    PubMed Central

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  15. Use of radiologic modalities in coccidioidal meningitis

    SciTech Connect

    Stadalnik, R.C.; Goldstein, E.; Hoeprich, P.D.; McGahan, J.P.

    1981-01-01

    The diagnostic utility of pentetate indium trisodium CSF studies, technetium Tc 99m brain scans, and computerized tomographic (CT) scans was evaluated in eight patients in whom coccidioidal meningitis developed following a dust storm in the Central Valley of California. The 111In flow studies and the CT scans demonstrated hydrocephalus in five patients with clinical findings suggesting this complication. Ventriculitis has not previously been diagnosed before death in patients with coccidioidal meningitis; however, it was demonstrated in two patients by the technetium Tc 99m brain scan. The finding that communicating hydrocephalus occurs early in meningitis and interferes with CSF flow into infected basilar regions has important therapeutic implications in that antifungal agents injected into the lumbar subarachnoid space may not reach these regions.

  16. Overcoming the stromal barrier for targeted delivery of HPMA copolymers to pancreatic tumors.

    PubMed

    Buckway, Brandon; Wang, Yongjian; Ray, Abhijit; Ghandehari, Hamidreza

    2013-11-01

    Delivery of macromolecules to pancreatic cancer is inhibited by a dense extracellular matrix composed of hyaluronic acid, smooth muscle actin and collagen fibers. Hyaluronic acid causes a high intratumoral fluidic pressure which prevents diffusion and penetration into the pancreatic tumor. This study involves the breaking down of hyaluronic acid by treating CAPAN-1 xenograft tumors in athymic nu/nu mice with targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers radiolabeled with (111)In for single photon emission computerized tomography (SPECT) imaging. Two targeting strategies were investigated including αvβ3 integrin and HER2 receptors. HPMA copolymers were targeted to these receptors by conjugating short peptide ligands cRGDfK and KCCYSL to the side chains of the copolymer. Results demonstrate that tumor targeting can be achieved in vivo after treatment with hyaluronidase. This approach shows promise for enhanced delivery of polymer-peptide conjugates to solid tumors.

  17. Pitfalls in establishing the diagnosis of deep venous thrombophlebitis by indium-111 platelet scintigraphy

    SciTech Connect

    Seabold, J.E.; Conrad, G.R.; Kimball, D.A.; Ponto, J.A.; Bricker, J.A.

    1988-07-01

    Forty-seven /sup 111/In-platelet scintigraphs (In-PS) were analyzed retrospectively to identify sources of diagnostic error and to optimize the diagnostic criteria for active deep venous thrombophlebitis (DVT). The results of In-PS were compared with contrast venography, additional diagnostic studies, and clinical outcome. Three patterns of platelet localization emerged as the best predictors of active DVT: (a) focal or (b) linear 4-hr localization, or (c) an asymmetric blood-pool pattern on 4-hr imaging that evolved into a focal or linear pattern by 16 to 24 hr. All false-positive studies had abnormal patterns confined to the inguinal region at 24 hr. All patients with false-negative studies had received heparin between 4 and 24 hr. The potential pitfalls encountered in the evaluation of the iliac, femoral, and popliteal veins are reviewed and the importance of delayed imaging in selected cases is emphasized.

  18. The electrochemical characterisation of benzyl mercaptan-modified Au(111): structure and copper deposition.

    PubMed

    Baunach, T; Kolb, D M

    2002-04-01

    The behaviour of benzyl mercaptan self-assembled monolayers on Au(111) in sulfuric acid solution was studied using cyclic voltammetry and in situ scanning tunnelling microscopy. Modification of the Au(111) surface in an ethanolic solution of benzyl mercaptan leads to a disordered monolayer. However, by partial reductive desorption a striped c (15 x sqrt [3]) and a (2 x sqrt [3]) structure were obtained. The disordered benzyl mercaptan film was also used for the study of copper deposition. At -0.02 V versus SCE, that is in the underpotential deposition region, monoatomic high islands appear on the surface. Bulk deposition of copper starts at -0.08 V versus SCE with the growth of dendrites underneath the thiol film. At higher overpotentials, the growth of three-dimensional copper clusters commences.

  19. In situ STM investigation of spinodal decomposition and surface alloying during underpotential deposition of Cd on Au(111) from an ionic liquid.

    PubMed

    Pan, Ge-Bo; Freyland, Werner

    2007-07-07

    The electrodeposition and anodic dissolution of Cd on Au(111) in an acidic chloroaluminate ionic liquid (MBIC-AlCl(3), 42 : 58 mol%) have been investigated by cyclic voltammetry and in situ STM. In the Cd underpotential deposition region, various nanostructures can be distinguished. At a potential of 0.95 V vs. Al/Al(iii), a transformation from a well ordered AlCl(4)(-) adlayer to a ( radical3 x radical19) superstructure, presumably due to Cd-AlCl(4)(-) coadsorption, is observed. Reducing the potential to 0.45 V, surface alloying of Cd and Au occurs, which is evidenced for the first time by typical spinodal structures occurring both during deposition and dissolution of the surface alloy layer having a hexagonal structure. At still lower potentials below 0.21 V, a layer-by-layer growth of bulk Cd sets in.

  20. Stick-slip behaviour on Au(111) with adsorption of copper and sulfate.

    PubMed

    Podgaynyy, Nikolay; Wezisla, Sabine; Molls, Christoph; Iqbal, Shahid; Baltruschat, Helmut

    2015-01-01

    Several transitions in the friction coefficient with increasing load are found on Au(111) in sulfuric acid electrolyte containing Cu ions when a monolayer (or submonolayer) of Cu is adsorbed. At the corresponding normal loads, a transition to double or multiple slips in stick-slip friction is observed. The stick length in this case corresponds to multiples of the lattice distance of the adsorbed sulfate, which is adsorbed in a √3 × √7 superstructure on the copper monolayer. Stick-slip behaviour for the copper monolayer as well as for 2/3 coverage can be observed at F N ≥ 15 nN. At this normal load, a change from a small to a large friction coefficient occurs. This leads to the interpretation that the tip penetrates the electrochemical double layer at this point. At the potential (or point) of zero charge (pzc), stick-slip resolution persists at all normal forces investigated.

  1. In-situ STM studies of thallium underpotential deposition on Au(111) single-crystal electrode in acid solution

    NASA Astrophysics Data System (ADS)

    Polewska, Wanda; Adzic, Radoslav

    1999-04-01

    The structure of electrodeposited Tl adlayers on Au(111) in 0.1 M. HClO4 has been investigated using in-situ scanning tunneling microscopy method. Incommensurate, rotated hexagonal (RHCP) Tl adlayer was found, within a wide potential window, between Tl bulk deposition at -0.7 V and -0.4 V. This adlayer is closely packed with Tl interatomic distance of 3.4 +/- 0.2 angstroms, its rotation from the gold substrate axis is 60 +/- 10 and its coverage is 0.74. At slightly more positive potentials, between -0.45 V and -0.37 V, low coverage 2 X 2 phase of Tl was found, coexisting together with RHCP monolayer. At the potential region between -0.35 V and 0.8 V both ordered Tl phases disappeared and instead the formation of considerable amount of pits at the surface has been observed.

  2. Role of ProstaScint for brachytherapy in localized prostate adenocarcinoma.

    PubMed

    Ellis, Rodney J; Kim, Edward; Foor, Ryan

    2004-07-01

    ProstaScint (CYT-356 or capromab pendetide, Cytogen) is an 111In-labeled monoclonal mouse antibody specific for prostate-specific membrane antigen, a prostate transmembrane glycoprotein that is upregulated in prostate adenocarcinoma. ProstaScint scans are US Food and Drug Administration approved for pretreatment evaluation of metastatic disease in high-risk patients. They are also approved for post-prostatectomy assessment of recurrent disease in patients with a rising prostate-specific antigen level. This review explores the literature on ProstaScint and its use in guiding the treatment of prostate cancer. A novel technique for identifying areas of cancer within the prostate using ProstaScint images fused with pelvic computed tomography scans is also described. The identification of areas of high antibody signal provides targets for radiotherapeutic dose escalation, with the overall goals of improving treatment outcome while preserving adjacent tissue structures and decreasing treatment morbidity.

  3. Platelet--arterial synthetic graft interaction and its modification

    SciTech Connect

    Callow, A.D.; Connolly, R.; O'Donnell, T.F. Jr.; Gembarowicz, R.; Keough, E.; Ramberg-Laskaris, K.; Valeri, C.R.

    1982-11-01

    We compared the in vivo platelet reactivity of two commonly used clinical grafts, Dacron and expanded polytetrafluoroethylene (PTFE), with that of a control autogenous artery graft and assessed whether platelet reactivity was modified by the platelet-antiaggregating agent prostacyclin (PGI2) (epoprostenol). Grafts were randomly placed into the carotid arteries of 21 baboons. Platelets labeled with /sup 111/In were infused within one hour after implantation graft for gamma camera scanning of platelet uptake. The accumulation of platelets on Dacron grafts began almost immediately after injection and reached a peak after one to two hours. The PTFE and control autogenous artery grafts accumulated comparable small amounts of platelets. Prostacyclin was then infused in a second series of baboons with Dacron grafts, at a rate of 150 to 200 ng/kg/min. It prevented the usual platelet uptake when administered concomitant with graft implantation and reduced previously established platelet activity.

  4. The LNLS soft X-ray spectroscopy beamline.

    PubMed

    Tolentino, H; Compagnon-Cailhol, V; Vicentin, F C; Abbate, M

    1998-05-01

    The soft X-ray spectroscopy beamline installed at a bending-magnet source at the LNLS is described. The optics are designed to cover energies from 800 to 4000 eV with good efficiency. The focusing element is a gold-coated toroidal mirror with an angle of incidence of 17 mrad. The UHV double-crystal monochromator has three pairs of crystals, Si (111), InSb (111) and beryl (101;0), that can be selected by a sliding movement. The UHV workstation is equipped with an ion gun, an electron gun, an electron analyser, LEED optics, an open channeltron and a photodiode array. This beamline is intended for photoemission, photoabsorption, reflectivity and dichroism experiments.

  5. Pollution level, phase distribution and health risk of polycyclic aromatic hydrocarbons in indoor air at public places of Hangzhou, China.

    PubMed

    Lu, Hao; Zhu, Lizhong; Chen, Shuguang

    2008-04-01

    PAHs pollution survey in air of public places was conducted in Hangzhou, China. The most serious PAHs pollution was observed in indoor air of shopping centers and the slightest was in train stations. The molecular weight of chrysene (MW 228) appeared to be the dividing line for the PAHs with a larger or smaller distribution in the vapor or particulate phase. Concentrations of 15 PAHs on PM2.5 accounted for 71.3% of total particulate PAHs, and followed by PM2.5-10 fraction (17.6%) and >PM10 fraction (11.1%). In shopping centers and supermarkets, emission of 2-4 rings PAHs occurred from indoor sources, whereas 5-6 rings PAHs predominantly originated from transport of outdoor air. In temples, PAHs in indoor air mainly originated from incense burning. Health risks associated with the inhalation of PAHs were assessed, and naphthalene made the greatest contribution (62.4%) to the total health risks.

  6. A quint-wavelength UV spectroscopy for simultaneous determination of dichlorobenzene, chlorobenzene, and benzene in simulated water reduced by nanoscale zero-valent Fe/Ni bimetal.

    PubMed

    Wan, Xiaofang; Liu, Yu; Chai, Xin-Sheng; Li, Youming; Guo, Congbao

    2017-03-18

    A quint-wavelength UV spectroscopy for rapid determination of dichlorobenzene (DCB), chlorobenzene (CB) and benzene (B) was developed for the dechlorination process of DCB reduced by nanoscale zero-valent Fe/Ni bimetal. Based on the absorbance measurements at 260, 269, 277, 290 and 300nm, the equations for calculating the concentration of DCB and CB and B were established, in which the spectral interference from the nanoparticles could be effectively minimized. The results show that the present method has a good measurement precision (the relative standard deviations are within 2.0%) and accuracy (the recoveries are between 89 and 111%) in the DCB, CB and B's quantification. The present method is simple, rapid, and such a methodology is very suitable to be used for evaluating the dechlorination performance of chlorinated aromatic compounds in the presence of bimetal nanoparticle.

  7. Differential reactivity of Cu(111) and Cu(100) during nitrate reduction in acid electrolyte.

    PubMed

    Bae, Sang-Eun; Gewirth, Andrew A

    2008-01-01

    The interactions of nitrate with Cu(100) and Cu(111) in acidic solution are studied by cyclic voltammetry (CV) and in situ electrochemical scanning tunneling microscopy (EC-STM). CV results show that reduction of nitrate on Cu(111) commences at 0.0 V vs. Ag/AgCl while the corresponding potential is -0.3 V on Cu(100). EC-STM images show that the terrace of both Cu(111) and Cu(100) are atomically flat at potentials more negative than -0.7 V. The Cu(100) surface exhibits flat terraces throughout the entire cathodic potential range. Close to OCP, step edges start to corrode. In contrast to Cu(100), the first layer of Cu(111) is converted to an atomically rough and defected surface-associated with nascent surface oxidation at potentials positive of -0.7 V. This surface oxidation is correlated with nitrate reduction.

  8. Intensified nitrogen removal of constructed wetland by novel integration of high rate algal pond biotechnology.

    PubMed

    Ding, Yi; Wang, Wei; Liu, Xingpo; Song, Xinshan; Wang, Yuhui; Ullman, Jeffrey L

    2016-11-01

    High rate algal pond (HRAP) was combined with constructed wetland (CW) to intensify nitrogen removal through optimizing nitrification and denitrification. Nitrification and denitrification process mainly depends on the oxygen content and carbon source level in CWs. Algal biomass was enriched in HRAP, and dissolved oxygen (DO) concentration was increased via photosynthesis. Algal debris increased COD as degradable bioresource. The results showed that HRAP-CW hybrid systems effectively promoted the nitrogen removal performance due to rich DO and COD. The extension of hydraulic retention time in HRAP significantly improved NH4-N and TN removals by 10.9% and 11.1% in hybrid systems, respectively. The highest NH4-N and TN removals in hybrid systems respectively reached 67.2% and 63.5%, which were significantly higher than those in single CW. The study suggested that the hybrid system had the application potentials in nitrogen removal from wastewater.

  9. Monte Carlo simulation of Auger-electron spectra.

    PubMed

    Grau Carles, A; Kossert, K

    2009-01-01

    A procedure to calculate the complex spectra of electron-capture nuclides which simultaneously eject several electrons and X-rays with different energies is presented. The model is applied to compute spectra of the radionuclides (125)I, (123)I and (111)In. The spectra are then compared with experimental spectra obtained by means of liquid scintillation counting. To this end, the computed spectra were transformed to allow for the nonlinear response function for a liquid scintillator, chemical quenching, as well as the Wallac-type amplifier used for the measurements. The calculated spectra are important for applications of free parameter models in liquid scintillation counting and also for studying the impact of electron-capture nuclides on DNA.

  10. Local symmetry lowering in CdMn{sub 2}O{sub 4} spinel

    SciTech Connect

    Oliveira, G. N. P.; Lopes, A. M. L.; Teixeira, R.; Silva, M. R.; Mendonça, T. M.; Araújo, J. P.; Correia, J. G.

    2014-12-14

    This work presents an atomic scale study of the electric field gradient (EFG) in the tetragonally distorted CdMn{sub 2}O{sub 4} spinel manganite. The EFG temperature dependence at the Cd and Mn sites was followed via perturbed angular correlation measurements with the {sup 111}In and {sup 111m}Cd probes, from 873 down to 12 K at Isolde-CERN. The results show that in the 12–600 K temperature range, a single Jahn-Teller distorted local phase exists. However above 100 K, a dynamic lattice distortion, evidenced by time dependent EFG fluctuations, sets in suggesting a structural instability. Above 600 K, a local MnO{sub 6} octahedra with relaxed Jahn-Teller distortions emerge and grow in the low temperature matrix, although no macroscopic tetragonal to cubic phase transition was observed.

  11. Effectiveness of ion implantation of iron garnet films

    SciTech Connect

    Tikhonov, A.N.; Fedichkin, G.M.; Yurchenko, S.E.; Suslin, L.A.; Smirnov, I.S.; Shlenov, Yu.V.

    1986-01-01

    The authors seek to determine experimentally what changes of the magnetic bubble properties and of the iron garnet film characteristics resulting from implantation of Ne/sup +/ ions can be used as criteria for assessing the effectiveness of this process in the production of bubble devices. For the experiments, the authors used (YBi)/sub 3/(FeGa)/sub 5/O/sub 12/; (TmBi)/sub 3/(FeGa)/sub 5/O/sub 12/; and (YSmLuCa)/sub 3/(FeGe)/sub 5/O/sub 12/. The orientation of the Gd/sub 3/Ga/sub 5/O/sub 12/ substrate is (111) in all cases. The current density of the H/sup +/ proton beam did not exceed 0.5 micro-A/cm/sup 2/.

  12. [Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies]. DOE annual report, 1994--95

    SciTech Connect

    DeNardo, S.J.

    1995-12-31

    The authors describe results which have not yet been published from their associated studies listed in the title. For the first, they discuss Lym-1 single chain genetically engineered molecules, analysis of molecular genetic coded messages to enhance tumor response, and human dosimetry and therapeutic human use radiopharmaceuticals. Studies in phantoms includes a discussion of planar image quantitation, counts coincidence correction, organ studies, tumor studies, and {sup 90}Y quantitation with Bremsstrahlung imaging. The study on SPECT discusses attenuation correction and scatter correction. Preclinical studies investigated uptake of {sup 90}Y-BrE-3 in mice using autoradiography. Clinical studies discuss image quantitation verses counts from biopsy samples, S factors for radiation dose calculation, {sup 67}Cu imaging studies for lymphoma cancer, and {sup 111}In MoAb imaging studies for breast cancer to predict {sup 90}Y MoAb therapy.

  13. Anomalous temperature dependence of the electric field gradient at the Y site in In/sub 0. 1/Y/sub 0. 9/Ba/sub 2/Cu/sub 3/O/sub 9-//sub delta/: Evidence for soft vibrational modes

    SciTech Connect

    Catchen, G.L.; Blaszkiewicz, M.; Baratta, A.J.; Huebner, W.

    1988-08-01

    Perturbed angular correlation (PAC) spectroscopy has been used to measure a well-defined static electric quadrupole interaction in a superconducting ceramic, In/sub 0.1/Y/sub 0.9/Ba/sub 2/Cu/sub 3/O/sub 9-//sub delta/. Perturbation functions, Fourier transforms, and the derived PAC parameters are given for data taken at temperatures ranging from 77 to 1070 K. Indirect evidence is presented for the occupation of the Y site by the /sup 111/In-/sup 111/Cd PAC probe. The derived electric field gradients were found to increase linearly with temperature. This result suggests the presence of soft, anisotropic vibrations in the structure. Additional evidence is presented to indicate that O/sup 2-/-ion or O-vacancy transport may not occur in the Y coordination sphere.

  14. The Cyclotron radionuclide program at King Faisal Specialist Hospital and Research Centre

    NASA Astrophysics Data System (ADS)

    Hupf, Homer B.; Tischer, Stephen D.; Al-Watban, Farouk

    1985-05-01

    The King Faisal Specialist Hospital and Research Centre Cyclotron is being used to produce radionuclides for nuclear medicine, short-lived positron emitters for positron emission tomography (PET) studies, neutrons for therapy and biological research. Radiopharmaceuticals for planar imaging at King Faisal Specialist Hospital and other hospitals in Saudi Arabia include thallous-201 chloride, gallium-67 citrate, sodium iodide 123I capsules, 123I orthoiodohippurate and 81mKr generators. Products from short-lived positron emitters such as 18F fluordeoxyglucose, 11C methionine, 15O carbon dioxide and 63Zn hematoporphyrin are prepared and used on site for physiological studies in a PET program. Several patients have been treated with neutron therapy and a program for studying neutron radiation effects on cells is underway. Radiopharmaceutical products under development include 111In-labelled monoclonal antibodies for specific tumor detection, 11C methylglucose for metabolic studies and 11C putrescine for tumor localization.

  15. Structural and optical characterization of indium-antimony complexes in ZnO

    NASA Astrophysics Data System (ADS)

    Türker, M.; Deicher, M.; Johnston, K.; Wolf, H.; Wichert, Th.

    2015-04-01

    One of the main obstacles to the technical application of the wide-gap semiconductor ZnO represents the difficulty to achieve reliable p-type doping of ZnO with group V elements (N, P, As, Sb) acting as acceptors located on O lattice sites. The theoretically proposed concepts of cluster-doping or codoping may lead to an enhanced and stable p-type conductivity of ZnO. We report on PAC results obtained by codoping experiments of ZnO by ion implantation using the donor 111In and the group-V acceptor Sb. The formation of In-Sb pairs has been observed. Based on these PAC results, there is no evidence for the formation of In-acceptor complexes involving more than one Sb acceptor. These results has been complemented by photoluminescence measurements.

  16. Imaging of platelets in right-sided extracardiac conduits in humans

    SciTech Connect

    Agarwal, K.C.; Wahner, H.W.; Dewanjee, M.K.; Fuster, V.; Puga, F.J.; Danielson, G.K.; Chesebro, J.H.; Feldt, R.H.

    1982-04-01

    As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with /sup 111/In-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

  17. Timing of Events in the Central Engine and Jets of the Radio Galaxies 3c 111 and 3c 120 (core Program)

    NASA Astrophysics Data System (ADS)

    The investigators request continuation of their long-term monitoring of the X-ray flux of the radio galaxies 3C 111 (FR 2) and 3C 120 (FR 1) 2 and 4 times per week, respectively, throughout Cycle 12, as well as a 90 days of daily monitoring of 3C 111. In both objects, dips in X-ray flux precede the appearance of bright superluminal knots in the radio jet. The long-term multiwaveband light curves and sequences of 7 mm VLBA images will record the changing pattern of multiwaveband emission in these two AGN. 3C 111 is a probable EGRET source; if the ID is correct, GLAST will measure its flux daily, allowing relative timing of gamma-ray variations with X-ray and optical events from the central engine plus radio events in the jet.

  18. Columnar epitaxy of hexagonal and orthorhombic silicides on Si(111)

    NASA Technical Reports Server (NTRS)

    Fathauer, R. W.; Nieh, C. W.; Xiao, Q. F.; Hashimoto, Shin

    1990-01-01

    Columnar grains of PtSi and CrSi2 surrounded by high-quality epitaxial silicon are obtained by ultrahigh vacuum codeposition of Si and metal in an approximately 10:1 ratio on Si(111) substrates heated to 610-840 C. This result is similar to that found previously for CoSi2 (a nearly-lattice-matched cubic-fluorite crystal) on Si(111), in spite of the respective orthorhombic and hexagonal structures of PtSi and CrSi2. The PtSi grains are epitaxial and have one of three variants of the relation defined by PtSi(010)/Si(111), with PtSi 001 line/Si 110 line type.

  19. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals.

    PubMed

    Zeng, Dexing; Zeglis, Brian M; Lewis, Jason S; Anderson, Carolyn J

    2013-06-01

    Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This review will focus on recent applications of click chemistry ligations in the preparation of imaging agents for SPECT and PET, including small molecules, peptides, and proteins labeled with radionuclides such as (18)F, (64)Cu, (111)In, and (99m)Tc.

  20. Adlayer structure of octa-alkoxy-substituted copper(II) phthalocyanine on Au(111) by electrochemical scanning tunneling microscopy.

    PubMed

    Wang, Li; Ou-Yang, Liangyue; Yau, Shueh-Lin

    2008-01-01

    Electrochemical scanning tunneling microscopy (ECSTM) has been used to examine the adlayer of octa-alkoxy-substituted copper(II) phthalocyanines (CuPc(OC(8)H(17))(8)) on Au(111) in 0.1 M HClO(4), where the molecular adlayer was prepared by spontaneous adsorption from a benzene solution containing this molecule. Topography STM scans revealed long-range ordered, interweaved arrays of CuPc(OC(8)H(17))(8) with coexistent rectangular and hexagonal symmetries. High-quality STM molecular resolution yielded the internal molecular structure and the orientation of CuPc(OC(8)H(17))(8) admolecules. These STM results could shed insight into the method of generating ordered molecular assemblies of phthalocyanine molecules with long-chained substitutes on metal surface.

  1. Intermixed adatom and surface-bound adsorbates in regular self-assembled monolayers of racemic 2-butanethiol on Au(111).

    PubMed

    Ouyang, Runhai; Yan, Jiawei; Jensen, Palle S; Ascic, Erhad; Gan, Shiyu; Tanner, David; Mao, Bingwei; Niu, Li; Zhang, Jingdong; Tang, Chunguang; Hush, Noel S; Reimers, Jeffrey R; Ulstrup, Jens

    2015-04-07

    In situ scanning tunneling microscopy combined with density functional theory molecular dynamics simulations reveal a complex structure for the self-assembled monolayer (SAM) of racemic 2-butanethiol on Au(111) in aqueous solution. Six adsorbate molecules occupy a (10×√3)R30° cell organized as two RSAuSR adatom-bound motifs plus two RS species bound directly to face-centered-cubic and hexagonally close-packed sites. This is the first time that these competing head-group arrangements have been observed in the same ordered SAM. Such unusual packing is favored as it facilitates SAMs with anomalously high coverage (30%), much larger than that for enantiomerically resolved 2-butanethiol or secondary-branched butanethiol (25%) and near that for linear-chain 1-butanethiol (33%).

  2. Adolescents with Turkish background in Norway and Sweden: a comparative study of their psychological adaptation.

    PubMed

    Virta, Erkki; Sam, David L; Westin, Charles

    2004-02-01

    Using a questionnaire survey, this study compared psychological adaptation (self-esteem, life satisfaction, and mental health problems) of Turkish adolescents in Norway and Sweden, and examined to what extent ethnic and majority identities, acculturation strategies, and perceived discrimination accounted for adaptation among Turkish adolescents. The samples consisted of 407 Turks (111 in Norway and 296 in Sweden) with a mean age of 15.2 years and 433 host adolescents (207 in Norway, 226 in Sweden) with a mean age of 15.6 years. Turks in Norway reported poorer psychological adaptation than Turks in Sweden. Predictors of good adaptation were Turkish identity and integration, whereas poor adaptation was related to marginalization and perceived discrimination. The results indicated that the poorer adaptation of Turks in Norway compared to that of Turks in Sweden could be due to lower degree of Turkish identity and higher degree of perceived discrimination.

  3. An in vitro method for assessing biomaterial-associated platelet activation.

    PubMed

    LaFayette, Nathan G; Skrzypchak, Amy M; Merz, Scott; Bartlett, Robert H; Annich, Gail M

    2007-01-01

    The development of a nonthrombogenic artificial surface for use with indwelling sensors or catheters remains an elusive goal despite decades of ongoing research. In vivo studies are both labor intensive and costly, and are therefore an inefficient way to rapidly screen possible surface materials. The following in vitro model used glass, polyvinyl chloride (PVC), and polypropylene test tubes incubated with 111In-labeled rabbit platelets and illustrated that, despite equivalent platelet count and function, platelet adhesion was greatest on glass (n = 13), with PVC (n = 17) at 67 +/- 8% and polypropylene (n = 13) at 43 +/- 5% when compared with glass. Extrapolating this method by coating test tubes with new, nonthrombogenic materials is a quick and reliable way to screen material before embarking upon more lengthy in vivo animal studies.

  4. Heteroepitaxial Growth of Ferromagnetic MnSb(0001) Films on Ge/Si(111) Virtual Substrates

    PubMed Central

    2013-01-01

    Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent. PMID:24409091

  5. Pleural liquid clearance rate measured in awake sheep by the volume of dilution method

    SciTech Connect

    Broaddus, V.C.; Wiener-Kronish, J.P.; Berthiaume, Y.; Staub, N.C.

    1986-03-01

    The authors reported 24h clearance of mock pleural effusions measured terminally in sheep. To measure effusion volume at different times in the same sheep, they injected /sup 111/In-transferrin and measured its dilution. In 5 sheep with effusions of known sizes, the method was accurate to +/-10%. In 5 awake sheep, the authors injected 10 ml/kg of a 1% protein solution via a non-penetrating rib capsule. At 6h, the authors measured the volume by the dilution method and at 24h by direct recovery. The clearance rate in each animal was constant at 2.9-6.0%/h (average 4.8 +/- 1.3%/h). This new method gives a reliable two point clearance rate and requires fewer animals.

  6. Live concerts reduce cancer inpatients' anxiety.

    PubMed

    Toccafondi, A; Bonacchi, A; Mambrini, A; Miccinesi, G; Prosseda, R; Cantore, M

    2016-10-10

    In Italy a new experience of music medicine called "The Music Givers" is spreading among Oncology Units; it aims to organise weekly live concerts (length 45-60 min) followed by a buffet. Purpose of the present study is to evaluate the effect of the format of The Music Givers on cancer in-patients' anxiety. State-Trait Anxiety Inventory (STAI-Y) was administered to 111 in-patients before and after the concerts. After the concerts we observed a 3.87 point decrease in state anxiety (p < .001) and statistically significant differences in most of the domains assessed by STAI-Y. These results invite a reflection on the importance of offering to inpatients events such as live music concerts, in order to improve their psychological condition during hospitalisation.

  7. Power laws governing epidemics in isolated populations

    NASA Astrophysics Data System (ADS)

    Rhodes, C. J.; Anderson, R. M.

    1996-06-01

    TEMPORAL changes in the incidence of measles virus infection within large urban communities in the developed world have been the focus of much discussion in the context of the identification and analysis of nonlinear and chaotic patterns in biological time series1-11. In contrast, the measles records for small isolated island populations are highly irregular, because of frequent fade-outs of infection12-14, and traditional analysis15 does not yield useful insight. Here we use measurements of the distribution of epidemic sizes and duration to show that regularities in the dynamics of such systems do become apparent. Specifically, these biological systems are characterized by well-defined power laws in a manner reminiscent of other nonlinear, spatially extended dynamical systems in the physical sciences16-19. We further show that the observed power-law exponents are well described by a simple lattice-based model which reflects the social interaction between individual hosts.

  8. In vivo and in vitro effects of dexamethasone on leukocyte migration in the rat adjuvant arthritis model

    SciTech Connect

    Thieme, T.R.; Mirkovich, A.; Maloney, P.; Goodwin, D.A.

    1982-12-01

    When polymorphonuclear leukocytes (PMNs) and mononuclear cells were isolated from the blood of dexamethasone-treated normal rats, in vitro mononuclear cell migration was inhibited and PMN migration was stimulated in comparison to controls. Inflammogen-induced PMNs showed inhibited cell migration due to dexamethasone treatment. Gamma camera imaging was then used to detect cells in vivo after labeling with /sup 111/In. When the dexamethasone-treated blood cells were injected into adjuvant arthritis diseased rats, mononuclear cells showed depressed migration into the inflamed paws, while PMNs showed stimulated migration into the inflamed paws in comparison to controls. When the recipient adjuvant arthritic animals were treated with dexamethasone, both normal mononuclear cell and normal PMN migration to the inflamed paws were inhibited.

  9. Li+-ion neutralization on metal surfaces and thin films

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Shen, Jie; Jia, Juanjuan; Kandasamy, Thirunavukkarasu; Bobrov, Kirill; Guillemot, Laurent; Fuhr, Javier. D.; Martiarena, Maria Luz; Esaulov, Vladimir A.

    2011-11-01

    Li+ ions with energies ranging from 0.3 to 2 keV are scattered from Au(110) and Pd(100) surfaces and from ultrathin Ag film grown on Au(111) in order to study electron transfer phenomena. We find that neutralization occurs quite efficiently and find an anomalous ion energy dependence of the neutral fraction for Au(110) and Pd(100) surfaces previously noted for Au(111). The dependence of the neutral fraction on the azimuthal angle of the Au(110) and Pd(100) surfaces is reported. In the case of Ag monolayer on Au(111), results are similar to the case of the Ag(111) surface. To understand the anomalous ion energy dependence, we present a theoretical study using density functional theory (DFT) and a linearized rate equation approach, which allows us to follow the Li charge state evolution for the (111) surfaces of Ag, Au, and Cu, and for the Ag-covered Au(111) surface.

  10. Local fields at nonmagnetic impurity sites in a perovskite La 0 . 7 Ca 0 . 3 MnO 3

    NASA Astrophysics Data System (ADS)

    Sato, W.; Komatsuda, S.; Osa, A.; Sato, T. K.; Ohkubo, Y.

    2016-12-01

    The magnetic hyperfine field and electric field gradient at the 111Cd(leftarrow ^{111m}Cd) and 111Cd(leftarrow ^{111}In) probe nuclei introduced in a perovskite manganese oxide La0.7Ca0.3MnO3 ( T C ˜ 250 K) were measured for the study of the local magnetism and structure by means of time-differential perturbed angular correlation spectroscopy. In the ferromagnetic phase at 77 K, a very slight supertransferred magnetic hyperfine field (SMHF) (< 0.014 T) combined with a well-defined electric field gradient was observed at the nonmagnetic 111Cd nucleus on the La/Ca A site. This observation suggests that the large magnetic hyperfine field ( B h f = 6.9 T) measured, in our previous work, at the 140Ce probe nucleus on the A site originates from the contribution of a 4 f spin oriented by the SMHF from adjacent Mn ions.

  11. A noninvasive scintigraphic assessment of the colonic transit of nondigestible solids in man

    SciTech Connect

    Stubbs, J.B.; Valenzuela, G.A.; Stubbs, C.C.; Croft, B.Y.; Teates, C.D.; Plankey, M.W.; McCallum, R.W. )

    1991-07-01

    A noninvasive, scintigraphic technique for quantifying large intestinal transit time that provides low radiation doses was developed. The scintigraphic large intestinal transit (SLIT) method uses a total of 100 microCi of 111In encapsulated in ten 2-cm nondigestible capsules, which are ingested after a 6-hr fast. Two hundred fifty microcuries of 99mTc-sulfur colloid were given to outline the gastrointestinal tract. Images were acquired at 4-hr intervals until all capsules were excreted. Normal volunteers (n = 10) consumed a standardized diet 2 days prior and during imaging. Segmental transit times were measured in the following: ascending, transverse, descending, recto-sigmoid colons; hepatic and splenic flexures. The radiation absorbed dose to the large intestine for the SLIT technique is less than half of that associated with other radiographic methods of colonic transit time measurement.

  12. Interferroelectric transition as another manifestation of intrinsic size effect in ferroelectrics

    NASA Astrophysics Data System (ADS)

    Narayan, Bastola; Sorb, Y. A.; Loukya, B.; Samanta, Atanu; Senyshyn, Anatoliy; Datta, Ranjan; Singh, Abhishek Kumar; Narayana, Chandrabhas; Ranjan, Rajeev

    2016-09-01

    In general, crystallite size reduction is known to suppress the ferroic order (polarization or magnetization) in ferroelectric and magnetic systems. Using free particles of a giant tetragonality (c /a -1 =0.18 ) ferroelectric alloy BiFe O3-PbTi O3 as the model system, here we show that the intrinsic size effect in ferroelectrics can as well manifest in terms of switching the ground state from one ferroelectric phase (tetragonal with polarization along [001]) to another ferroelectric phase (rhombohedral with polarization along [111]). In this particular case, because of the strong coupling of the magnetic and structural degrees of freedom, a magnetic order also sets in below the critical size, making it a size induced magnetoferroelectric transformation. The driving force for this unusual transformation is argued to be the large depolarizing and domain wall energies in the tetragonal phase.

  13. Structural and Electrical Properties of Lithium-Ion Rechargeable Battery Using the LiFePO4/Carbon Cathode Material.

    PubMed

    Kim, Young-Sung; Jeoung, Tae-Hoon; Nam, Sung-Pill; Lee, Seung-Hwan; Kim, Jea-Chul; Lee, Sung-Gap

    2015-03-01

    LiFePO4/C composite powder as cathode material and graphite powder as anode material for Li-ion batteries were synthesized by using the sol-gel method. An electrochemical improvement of LiFePO4 materials has been achieved by adding polyvinyl alcohol as a carbon source into as-prepared materials. The samples were characterized by elemental analysis (EA), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-EM). The chemical composition of LiFePO4/C powders was in a good agreement with that of the starting solution. The capacity loss after 500 cycles of LiFePO4/C cell is 11.1% in room temperature. These superior electrochemical properties show that LiFePO4/C composite materials are promising candidates as cathode materials.

  14. Surface alloying of Pb on Cu(111): a TEAS study

    NASA Astrophysics Data System (ADS)

    de Beauvais, Ch.; Girard, Y.; Pérard, C.; Croset, B.; Mutaftschiev, B.

    1996-11-01

    Thermal energy atom scattering on vacuum deposited Pb submonolayers on Cu(111) in close to equilibrium conditions, at substrate temperatures between 303 K and 413 K, gives evidence for: (a) decoration by Pb atoms of monatomic steps on the Cu surface at degree of coverage 0 < θ < 0.004; (b) formation of disordered surface alloy in the first lattice plane of the copper substrate in the coverage range 0.004 < θ < 0.21; (c) formation of non-alloyed Pb layer with a p(4 × 4) structure above this coverage, up to the monolayer ( θ ≈ 0.56). The latter transition is shown to be of first order. The role of the deposition kinetics in far from equilibrium conditions is pointed out.

  15. Bridging the pressure gap: In situ atomic-level investigations of model platinum catalyst surfaces under reaction conditions by scanning tunneling microscopy

    SciTech Connect

    McIntyre, Brian James

    1994-05-01

    Results of this thesis show that STM measurements can provide information about the surfaces and their adsorbates. Stability of Pt(110) under high pressures of H2, O2, and CO was studied (Chap. 4). In situ UHV and high vacuum experiments were carried out for sulfur on Pt(111) (Chap.5). STM studies of CO/S/Pt(111) in high CO pressures showed that the Pt substrate undergoes a stacking-fault-domain reconstruction involving periodic transitions from fcc to hcp stacking of top-layer atoms (Chap.6). In Chap.7, the stability of propylene on Pt(111) and the decomposition products were studied in situ with the HPSTM. Finally, in Chap.8, results are presented which show how the Pt tip of the HPSTM was used to locally rehydrogenate and oxidize carbonaceous clusters deposited on the Pt(111) surface; the Pt tip acted as a catalyst after activation by short voltage pulses.

  16. Improving diagnosis of appendicitis. Early autologous leukocyte scanning.

    PubMed

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I

    1989-10-01

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  17. Theranostic etoposide phosphate/indium nanoparticles for cancer therapy and imaging

    NASA Astrophysics Data System (ADS)

    Srinivas, Ramishetti; Satterlee, Andrew; Wang, Yuhua; Zhang, Yuan; Wang, Yongjun; Huang, Leaf

    2015-11-01

    Etoposide phosphate (EP), a water-soluble anticancer prodrug, is widely used for treatment of many cancers. After administration it is rapidly converted to etoposide, its parent compound, which exhibits anticancer activity. Difficulty in parenteral administration necessitates the development of a suitable nanoparticle delivery system for EP. Here we have used indium both as a carrier to deliver etoposide phosphate to tumor cells and as a SPECT imaging agent through incorporation of 111In. Etoposide phosphate was successfully encapsulated together with indium in nanoparticles, and exhibited dose dependent cytotoxicity and induction of apoptosis in cultured H460 cancer cells via G2/M cell cycle arrest. In a mouse xenograft lung cancer model, etoposide phosphate/indium nanoparticles induce tumor cell apoptosis, leading to significant enhancement of tumor growth inhibition compared to the free drug.

  18. Facet-Dependent Catalytic Activity of Platinum Nanocrystals for Triiodide Reduction in Dye-Sensitized Solar Cells

    PubMed Central

    Zhang, Bo; Wang, Dong; Hou, Yu; Yang, Shuang; Yang, Xiao Hua; Zhong, Ju Hua; Liu, Jian; Wang, Hai Feng; Hu, P.; Zhao, Hui Jun; Yang, Hua Gui

    2013-01-01

    Platinum (Pt) nanocrystals have demonstrated to be an effective catalyst in many heterogeneous catalytic processes. However, pioneer facets with highest activity have been reported differently for various reaction systems. Although Pt has been the most important counter electrode material for dye-sensitized solar cells (DSCs), suitable atomic arrangement on the exposed crystal facet of Pt for triiodide reduction is still inexplicable. Using density functional theory, we have investigated the catalytic reaction processes of triiodide reduction over {100}, {111} and {411} facets, indicating that the activity follows the order of Pt(111) > Pt(411) > Pt(100). Further, Pt nanocrystals mainly bounded by {100}, {111} and {411} facets were synthesized and used as counter electrode materials for DSCs. The highest photovoltaic conversion efficiency of Pt(111) in DSCs confirms the predictions of the theoretical study. These findings have deepened the understanding of the mechanism of triiodide reduction at Pt surfaces and further screened the best facet for DSCs successfully. PMID:23670438

  19. The NIST radioactivity measurement assurance program for the radiopharmaceutical industry.

    PubMed

    Cessna, Jeffrey T; Golas, Daniel B

    2012-09-01

    The National Institute of Standards and Technology (NIST) maintains a program for the establishment and dissemination of activity measurement standards in nuclear medicine. These standards are disseminated through Standard Reference Materials (SRMs), Calibration Services, radionuclide calibrator settings, and the NIST Radioactivity Measurement Assurance Program (NRMAP, formerly the NEI/NIST MAP). The MAP for the radiopharmaceutical industry is described here. Consolidated results show that, for over 3600 comparisons, 96% of the participants' results differed from that of NIST by less than 10%, with 98% being less than 20%. Individual radionuclide results are presented from 214 to 439 comparisons, per radionuclide, for (67)Ga, (90)Y, (99m)Tc, (99)Mo, (111)In, (125)I, (131)I, and (201)Tl. The percentage of participants results within 10% of NIST ranges from 88% to 98%.

  20. Effect of storage and cooking on the fatty acid profile of omega-3 enriched eggs and pork meat marketed in Belgium

    PubMed Central

    Douny, Caroline; El Khoury, Rawad; Delmelle, Julien; Brose, François; Degand, Guy; Moula, Nassim; Farnir, Frédéric; Clinquart, Antoine; Maghuin-Rogister, Guy; Scippo, Marie-Louise

    2015-01-01

    The fatty acids (FA) profile was determined in n-3 enriched (Columbus™) Belgian eggs and pork in order to evaluate to what extent the n-3 fatty acids, which are very sensitive to oxidation, are resistant to storage or cooking. In standard eggs or pork, no change of the fatty acid profile was observed after storage or cooking without culinary fat, as well as in Columbus™ eggs and pork after storage. Some cooking processes (eggs in custard and meat in oven) induced a slight significant loss of n-3 fatty acids in Columbus™ eggs or pork (11.1% in fat from eggs cooked in custard vs. 15.3% in raw Columbus™ eggs and 11.0% in fat from oven cooked meat vs. 11.6% in raw Columbus™ meat). As expected, when Columbus™ pork is cooked with culinary fat, its fatty acid profile is modified according to the nature of the fat used. PMID:25838892

  1. Magnetic hyperfine interactions on Cd sites of the rare-earth cadmium compounds R Cd (R =Ce , Pr, Nd, Sm, Gd, Tb, Dy, Ho, and Er)

    NASA Astrophysics Data System (ADS)

    Cavalcante, F. H. M.; Leite Neto, O. F. L. S.; Saitovitch, H.; Cavalcante, J. T. P. D.; Carbonari, A. W.; Saxena, R. N.; Bosch-Santos, B.; Pereira, L. F. D.; Mestnik-Filho, J.; Forker, M.

    2016-08-01

    This paper reports the investigation of the magnetic hyperfine field Bh f in a series of rare-earth (R ) cadmium intermetallic compounds R Cd and GdCd2 measured by perturbed angular correlation (PAC) spectroscopy using 111In/111Cd as probe nuclei at Cd sites as well as first-principles calculations of Bh f at Cd sites in the studied compounds. Vapor-solid state reaction of R metals with Cd vapor and the 111In radioisotope was found to be an appropriate route of doping rare-earth cadmium compounds with the PAC probe 111In/111Cd. The observation that the hyperfine parameters depend on details of the sample preparation provides information on the phase preference of diffusing 111In in the rare-earth cadmium phase system. The 111Cd hyperfine field has been determined in the compounds R Cd for the R constituents Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, and Er, in several cases as a function of temperature. For most R constituents, the temperature dependence Bh f(T ) of 111Cd:R Cd is consistent with ferromagnetic order of the compound. DyCd, however, presents a remarkable anomaly: a finite magnetic hyperfine field is observed only in the temperature interval 35 K ≤ T ≤ 80 K which indicates a transition from ferromagnetic order to a spin arrangement where all 4 f -induced contributions to the magnetic hyperfine field at the Cd site cancel. First-principles calculation results for DyCd show that the (π , π , 0) antiferromagnetic configuration is energetically more favorable than the ferromagnetic. The approach used in the calculations to simulate the R Cd system successfully reproduces the experimental values of Bh f at Cd sites and shows that the main contribution to Bh f comes from the valence electron polarization. The de Gennes plot of the hyperfine field Bh f of 111Cd:R Cd vs the 4 f -spin projection (g -1 )J reflects a decrease of the strength of indirect 4 f -4 f exchange across the R series. Possible mechanisms are discussed and the experimental results indicate that

  2. PRESENT STATUS OF CHARGE-BREEDING IN KEKCB AT TRIAC

    SciTech Connect

    Oyaizu, M.; Jeong, S. C.; Imai, N.; Fuchi, Y.; Hirayama, Y.; Ishiyama, H.; Miyatake, H.; Okada, M.; Watanabe, Y. X.; Ichikawa, S.; Kabumoto, H.; Matsuda, M.; Osa, A.; Otokawa, Y.

    2009-05-04

    We report a recent experiment about the measurement of wall distribution of ions externally injected for charge-breeding in an electron cyclotron resonance (ECR) ion source. The ions, radioactive and singly charged {sup 111}In, were injected into the ECR ion source (ECRIS) for breeding their charge states at the Tokai Radioactive Ion Accelerator Complex (TRIAC). The residual radioactivity on the wall of the ECR plasma chamber of the source was measured, giving a two-dimensional distribution of the ions failed to be re-extracted during charge breeding. The distribution was decomposed, according to azimuthal symmetry, into three components, asymmetric, 120-degree symmetric, and isotropic ones, whose origins were qualitatively discussed for clarifying ion-losses in the course of charge breeding in ECRIS.

  3. The control of Varroa destructor using oxalic acid.

    PubMed

    Gregorc, Ales; Planinc, I

    2002-05-01

    Twenty-four honeybee (Apis mellifera) colonies were used to monitor the efficacy of a solution of 2.9% oxalic acid (OA) and 31.9% sugar against the mite Varroa destructor. Mite mortality was established prior to and after OA treatments, which were conducted in August and September. The treatments resulted in 37% mite mortality as opposed to 1.11% in the controls. OA treatment conducted in September on previously untreated colonies resulted in 25% mite mortality. OA treatments in October and November resulted in approximately 97% mite mortality. These results suggest that OA is effective during the broodless period and less effective when applied to colonies with capped broods. The possible use of OA against the Varroa mite in honeybee colonies as an alternative to routine chemical treatments is discussed.

  4. Correlation of urinary thioethers with chemical exposure in a rubber plant.

    PubMed Central

    Kilpikari, I

    1981-01-01

    Exposure to potentially alkylating in a rubber factory was measured by determining thioether concentrations in urine samples collected at the end of work on a Friday. The study population consisted of the total work force (113) in the production departments of a factory, and office clerks (111) in two factories of the same company. The highest excretion of thioethers was detected in female workers in the belt department who were exposed through the palmar skin. High excretion was also found in workers exposed to air-borne contaminants in the calender department and in workers in the raw material stores and chemical mixing sections. Lower values were found in this dispatching station and in the contaminant-free offices. Urinary thioether determination appears to be a reliable and easy method of assessing the exposure to certain rubber chemicals. PMID:7470409

  5. Identification of New Structural Fragments for the Design of Lactate Dehydrogenase A Inhibitors

    PubMed Central

    Nilov, D.K.; Kulikov, A.V.; Prokhorova, E.A.; Švedas, V.K.

    2016-01-01

    Human lactate dehydrogenase A plays an important role in the glucose metabolism of tumor cells and constitutes an attractive target for chemotherapy. Molecular fragments able to bind in the active site of this enzyme and form hydrogen bonds with the Arg168 guanidinium group, as well as additional interactions with the loop 96–111 in the closed conformation, have been identified by virtual screening of sulfonates and experimental testing of their inhibitory effect. The sulfo group can occupy a similar position as the carboxyl group of the substrate and its structural analogs, whereas the benzothiazole group attached via a linker can be located in the coenzyme (NADH) binding site. Thus, the value of merging individual structural elements of the inhibitor by a linker was demonstrated and ways of further structural modification for the design of more effective inhibitors of lactate dehydrogenase A were established. PMID:27795851

  6. Effect of polymer electrolyte on the performance of natural dye sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Adel, R.; Abdallah, T.; Moustafa, Y. M.; Al-sabagh, A. M.; Talaat, H.

    2015-10-01

    Polymer electrolyte based on polyacrylonitrile (PAN), Ethylene Carbonate (EC) and Acetonitrile (ACN) mixed with Potassium Iodide and Iodine in liquid and thin film forms were employed in natural dye sensitized solar cells (NDSSCs). Three natural dyes; black berry, hibiscus and rose are used as the sensitizing dye. The NDSSCs used, follow the configuration: FTO/TiO2/Natural Dye/Electrolyte/ Carbon/FTO. The liquid form polymer electrolyte with black berry natural dye gives an increase of 111% in short circuit photocurrent density (Jsc), 17.5% to open circuit voltage (Voc), fill factor of 0.57 ± 0.05 and three times increase in the conversion efficiency of 0.242 ± 0.012% compared to the iodine electrolyte.

  7. Stick–slip behaviour on Au(111) with adsorption of copper and sulfate

    PubMed Central

    Podgaynyy, Nikolay; Wezisla, Sabine; Molls, Christoph; Iqbal, Shahid

    2015-01-01

    Summary Several transitions in the friction coefficient with increasing load are found on Au(111) in sulfuric acid electrolyte containing Cu ions when a monolayer (or submonolayer) of Cu is adsorbed. At the corresponding normal loads, a transition to double or multiple slips in stick–slip friction is observed. The stick length in this case corresponds to multiples of the lattice distance of the adsorbed sulfate, which is adsorbed in a √3 × √7 superstructure on the copper monolayer. Stick–slip behaviour for the copper monolayer as well as for 2/3 coverage can be observed at F N ≥ 15 nN. At this normal load, a change from a small to a large friction coefficient occurs. This leads to the interpretation that the tip penetrates the electrochemical double layer at this point. At the potential (or point) of zero charge (pzc), stick–slip resolution persists at all normal forces investigated. PMID:25977853

  8. Influence of restraint and thermal exposure on welds in T-111 and ASTAR-811C

    NASA Technical Reports Server (NTRS)

    Gold, R. E.; Lessmann, G. G.

    1971-01-01

    The notched-tensile, tensile, and bend properties of GTA welds in T-111 and ASTAR-811C sheet were determined following a wide range of thermal exposures in order to define changes in ductility and mechanical property behavior due to weld aging response. No notch sensitivity or unusual tensile response was noted for any of the conditions evaluated. An aging response was noted for the bend ductile-brittle transition temperature determinations on both T-111 and ASTAR-811C welds. A tentative explanation for the observed response of each alloy is presented. In addition, the interrelationship of mechanical and chemical factors leading to underbead cracking in T-111 was investigated. The problem was shown to be amenable primarily to chemical solutions, such as alloy compositional changes. This was demonstrated by the improved performance of ASTAR-811C over T-111 in plate weld studies. Only modest success was achieved using procedural techniques as a means of eliminating underbead cracking.

  9. Hexagonal boron nitride cover on Pt(111): a new route to tune molecule-metal interaction and metal-catalyzed reactions.

    PubMed

    Zhang, Yanhong; Weng, Xuefei; Li, Huan; Li, Haobo; Wei, Mingming; Xiao, Jianping; Liu, Zhi; Chen, Mingshu; Fu, Qiang; Bao, Xinhe

    2015-05-13

    In heterogeneous catalysis molecule-metal interaction is often modulated through structural modifications at the surface or under the surface of the metal catalyst. Here, we suggest an alternative way toward this modulation by placing a two-dimensional (2D) cover on the metal surface. As an illustration, CO adsorption on Pt(111) surface has been studied under 2D hexagonal boron nitride (h-BN) overlayer. Dynamic imaging data from surface electron microscopy and in situ surface spectroscopic results under near ambient pressure conditions confirm that CO molecules readily intercalate monolayer h-BN sheets on Pt(111) in CO atmosphere but desorb from the h-BN/Pt(111) interface even around room temperature in ultrahigh vacuum. The interaction of CO with Pt has been strongly weakened due to the confinement effect of the h-BN cover, and consequently, CO oxidation at the h-BN/Pt(111) interface was enhanced thanks to the alleviated CO poisoning effect.

  10. Sub-monolayer film growth of a volatile lanthanide complex on metallic surfaces

    PubMed Central

    Chen, Jinjie; Edelmann, Kevin; Wulfhekel, Wulf

    2015-01-01

    Summary We deposited a volatile lanthanide complex, tris(2,2,6,6-tetramethyl-3,5-heptanedionato)terbium(III), onto metal surfaces of Cu(111), Ag(111) and Au(111) in vacuum and observed well-ordered sub-monolayer films with low temperature (5 K) scanning tunneling microscopy. The films show a distorted three-fold symmetry with a commensurate structure. Scanning tunneling spectroscopy reveals molecular orbitals delocalized on the ligands of the molecule. Our results imply that this complex can be transferred onto the metal substrates without molecular decomposition or contamination of the surface. This new rare-earth-based class of molecules broadens the choice of molecular magnets to study with scanning tunneling microscopy. PMID:26733215

  11. Site-specific conjugation of chain-terminal chelating polymers to Fab' fragments of anti-CEA mAb: effect of linkage type and polymer size on conjugate biodistribution in nude mice bearing human colorectal carcinoma.

    PubMed

    Slinkin, M A; Curtet, C; Sai-Maurel, C; Gestin, J F; Torchilin, V P; Chatal, J F

    1992-01-01

    Polylysine-based chelating polymers were used for site-specific modification of anti-CEA mAb Fab' fragments via their SH group distal to the antigen-binding site of the antibody molecule. Conjugation was performed using chain-terminal (pyridyldithio)propionate or 4-(p-maleimidophenyl)butyrate moieties to form reducible (S-S) or stable (S-C) bonds between a polymer and Fab' molecule, respectively. One S-S conjugate (S-S9) and two different S-C conjugates (S-C3 and S-C9) were prepared using 3- and 9-kDa molecular weight polymers. No significant loss of immunoreactivity was observed in solid-phase immunoassay, 90-95% of 111In-labeled conjugates being bound to CEA-coated Sepharose beads. After labeling with 111In, the conjugates had a specific radioactivity of 90-120 microCi/micrograms. Injected in nude mice bearing LS 174T carcinoma, the conjugates produced different biodistribution patterns. S-S9 was practically unable to accumulate in tumor and produced very rapid blood clearance of radioactivity and high uptake of radioactivity in liver, spleen, and especially kidneys (225% ID/g 24 h postinjection). S-C3 and S-C9 produced practically the same blood clearances (much slower than that of S-S9) and significant tumor uptake (9-10% ID/g at 24 h). S-C3 gave significantly lower radioactivity in spleen, skin, and bones, and cleared more rapidly from liver and kidneys. Renal uptake for S-C3 and S-C9 was rather high (45% ID/g at 24 h), but much lower than for S-S9.

  12. MONODISPERSED PEG-DOTA CONJUGATED ANTI-TAG-72 DIABODY HAS LOW KIDNEY UPTAKE AND HIGH TUMOR TO BLOOD RATIOS RESULTING IN IMPROVED 64Cu PET IMAGING

    PubMed Central

    Li, Lin; Turatti, Fabio; Crow, Desiree; Bading, James R.; Anderson, Anne-Line; Poku, Erasmus; Yazaki, Paul J.; Williams, Lawrence E.; Tamvakis, Debra; Sanders, Paul; Leong, David; Raubitschek, Andrew; Hudson, Peter J.; Colcher, David; Shively, John E.

    2011-01-01

    Diabodies are non-covalent dimers of single chain antibody fragments (scFvs) that retain the avidity of intact IgG but have more favorable blood clearance than intact IgGs. Radiometals offer a wide range of half lives and emissions for matching imaging and therapy requirements and provide facile labeling of chelate-antibody conjugates. However, due to their high retention and metabolism in the kidney, use of radiometal labeled diabodies can be problematic for both imaging and therapy. Methods Having previously shown that 111In-DOTA-PEG3400-anti-CEA-diabody has similarly high tumor uptake and retention and less than 50% as much kidney uptake and retention as non-PEGylated diabody, we synthesized a similar derivative for an anti-TAG-72-diabody. We also reduced the molecular size of the polydispersed PEG3400 to monodispersed PEG27 and PEG12 (nominal masses of 1188 and 528, respectively). We performed biodistributions of their DOTA conjugates radiolabeled with 125I, 111In, or 64Cu in tumor bearing athymic mice. Results Addition of PEG3400 to the diabody reduced kidney uptake to a level (≈10 %ID/g) comparable to that obtained with radiometal labeled intact IgG. The PEG27 and PEG12 diabody conjugates also demonstrated low kidney uptake without reduction of tumor uptake or tumor to blood ratios. When radiolabeled with 64Cu, the DOTA-PEG12- and PEG27-diabody conjugates gave high contrast PET images of colon cancer xenografts in athymic mice. Conclusion PEGylated diabodies may be a valuable platform for delivery of radionuclides and other agents to tumors. PMID:20554731

  13. Color Doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells.

    PubMed

    Liberman, Alexander; Wu, Zhe; Barback, Christopher V; Viveros, Robert; Blair, Sarah L; Ellies, Lesley G; Vera, David R; Mattrey, Robert F; Kummel, Andrew C; Trogler, William C

    2013-07-23

    Perfluoropentane gas filled iron-silica nanoshells have been developed as stationary ultrasound contrast agents for marking tumors to guide surgical resection. It is critical to establish their long-term imaging efficacy, as well as biodistribution. This work shows that 500 nm Fe-SiO2 nanoshells can be imaged by color Doppler ultrasound over the course of 10 days in Py8119 tumor bearing mice. The 500 nm nonbiodegradable SiO2 and biodegradable Fe-SiO2 nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with (111)In(3+) for biodistribution studies in nu/nu mice. The majority of radioactivity was detected in the liver and kidneys following intravenous (IV) administration of nanoshells to healthy animals. By contrast, after nanoshells were injected intratumorally, most of the radioactivity remained at the injection site; however, some nanoshells escaped into circulation and were distributed similarly as those given intravenously. For intratumoral delivery of nanoshells and IV delivery to healthy animals, little difference was seen between the biodistribution of SiO2 and biodegradable Fe-SiO2 nanoshells. However, when nanoshells were administered IV to tumor bearing mice, a significant increase was observed in liver accumulation of SiO2 nanoshells relative to biodegradable Fe-SiO2 nanoshells. Both SiO2 and Fe-SiO2 nanoshells accumulate passively in proportion to tumor mass, during intravenous delivery of nanoshells. This is the first report of the biodistribution following intratumoral injection of any biodegradable silica particle, as well as the first report demonstrating the utility of DTPA-(111)In labeling for studying silica nanoparticle biodistributions.

  14. Triple Therapy of HER2(+) Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

    PubMed

    Zolata, Hamidreza; Afarideh, Hossein; Davani, Fereydoun Abbasi

    2016-11-01

    By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2(+) cells and tumor (HER2(+))-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) (111)In-labeled, antibody-conjugated surface-modified SPIONs; and (4) (111)In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

  15. [Comparison of human papilloma virus infection status between men who have sex with men recruited from gay bathhouses and HIV voluntary counseling and testing clinics respectively in Urumqi].

    PubMed

    Tian, T; Cai, A J; Huang, B X; Abidan, Ainiwaer; Wang, H; Dai, J H

    2017-01-10

    Objective: To understand the human papilloma virus (HPV) infection status in men who have sex with men (MSM) recruited from gay bathhouses and HIV voluntary counseling and testing (VCT) clinics in Urumqi, Xinjiang Uygur autonomous region, and identify the associated risk factors. Methods: A total of 200 MSM aged ≥18 years were recruited by using the " snowballing" sampling method from gay bathhouses and VCT clinics in Urumqi during March-May, 2016. The MSM recruited completed questionnaires after filling in the informed consent form. The information about their demographic characteristics and sexual behaviors were collected, and anal swabs were collected from them for HPV genotyping. Results: The overall HPV infection rate was 54.0%. The HPV infection rate was 66.7%(74/111) in MSM from gay bathhouses and 38.2%(34/89) in MSM from VCT clinics and the high risk type HPV infection rate was 39.6% (44/111) in MSM from gay bathhouses and 14.6% (13/89) in MSM from VCT clinics, the differences were significant (χ(2)=16.112, P<0.05; χ(2)=15.190, P<0.05). Multiple logistic regression analysis indicated that the major risk factors for HPV infection included activity in gay bathhouse (OR=3.732, 95% CI: 1.950-7.141) and anal sexual behavior (OR=2.555, 95%CI: 1.329-4.912). Conclusion: The prevalence of HPV in MSM from gay bathhouses was higher than that in MSM from VCT clinics, indicating that close attention should be paid to the behavior intervention in MSM.

  16. Effect of intravascular neutrophil chemotactic factors on blood neutrophil and platelet kinetics

    SciTech Connect

    Issekutz, A.C.; Ripley, M.

    1986-02-01

    Intravenous infusion of an analogue (f-met-leu-phe (FMLP)) of a bacterial-derived polymorphonuclear leukocyte (PMNL) chemotactic factor, or of the complement-derived chemotactic stimulus, zymosan-activated plasma (ZAP, containing C5ades Arg) into rabbits induces acute PMNL margination in the pulmonary vasculature. The pulmonary PMNL sequestration is accompanied by thrombocytopenia. Because of the role platelets and PMNLs play in hemostasis and defense against infection, we studied the fate of these blood elements following sequestration induced by chemotactic factors. By employing 111In-labelled platelets and external radioisotope scanning, platelets were found to sequester in the pulmonary vasculature during FMLP infusion. Simultaneous 51Cr PMNL and 111In-platelet studies showed that following sequestration, PMNLs returned to the circulation and disappeared with a normal half-life (T1/2) whereas the T1/2 of the platelets was markedly shortened (T1/2 of control = 49 +/- 3.0 hr; FMLP or ZAP infused T1/2 = 27 +/- 2.7 hr). Infusion of platelet-activating factor (PAF) induced PMN and platelet sequestration with similar abnormalities in platelet kinetics. Studies with 51Cr- and 14C-serotonin-labelled platelets showed that platelets did not release serotonin during FMLP, ZAP, or low dose PAF-induced sequestration. In contrast to platelet survival, platelet size, platelet aggregation responses, and platelet glycoproteins were not affected by transient sequestration. These results indicate that during PMNL margination induced by relatively pure PMNL stimuli such as FMLP, platelets may reversibly marginate and subsequently be cleared at an accelerated rate. The reason for accelerated platelet clearance is not a result of circulating platelet aggregates or detectable proteolytic modification of membrane glycoproteins.

  17. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    SciTech Connect

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

    1987-04-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 (/sup 111/In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous /sup 111/In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures.

  18. Use of indium-111-labeled cells in measurement of cellular dynamics of experimental cardiac allograft rejection

    SciTech Connect

    Oluwole, S.; Wang, T.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.; Hardy, M.A.

    1981-01-01

    This study evaluates the kinetics and utility of infused indium-111-labeled cells in detecting rejection in ACI to Lewis rat heart allografts. Syngeneic leukocytes, lymph node lymphocytes, and platelets were isolated and labeled with indium-111 (/sup 111/In) oxine, respectively, and were infused i.v. into Lewis rats carrying beating ACI or syngeneic hearts from post-transplant days 0 to 6. Recipients were imaged serially at 24 hr after infusion of labeled cells followed by excision of both native and transplanted hearts for direct isotope count. Labeled leukocytes accumulative progressively in the allograft with the scan becoming positive by post-transplant day 4. The ratio of allograft to native heart isotope counts rose from 1.25 on day 1 to 10.07 (P less than 0.0001) on day 7. The Lewis recipients infused with labeled lymphocytes showed a positive scan on days 6 and 7 whereas the allograft to native heart isotope count ratio rose from 0.97 on day 1 to 5.33 (P less than 0.001) on day 7. Recipients infused with /sup 111/In-labeled platelets showed a positive scan on days 5 to 7 and the allograft to native heart isotope count ratio rose sharply from 2.56 on day 4 to 16.98 (P less than 0.005) on day 7. Syngeneic heart grafts failed to demonstrate significant accumulation of any of the labeled cell population. These studies confirm the importance of nonlymphocytic cells in cellular rejection, evaluate the kinetics of graft invasion by the various cell types, and suggest that the techniques used afford a method for a safe and an early detection of allograft rejection.

  19. Indium-111-antimyosin and iodine-123-MIBG studies in early assessment of doxorubicin cardiotoxicity

    SciTech Connect

    Carrio, I.; Estorch, M.; Berna, L.

    1995-11-01

    Detection of myocyte cell damage with {sup 111}In-antimyosin and impairment of adrenergic neuron function with MIBG during doxorubicin administration may provide early identification of patients at risk of significant functional impairment. We studied 36 cancer patients who underwent chemotherapy, including doxorubicin, to assess MIBG and {sup 111}In-antimyosin uptake in the course of doxorubicin administration. MIBG scans, antimyosin scans and ejection fraction measurements were performed before chemotherapy, at intermediate cumulative doses and at maximal cumulative doses of doxorubicin. MIBG uptake was quantified by a heart-to-mediastinum ratio and antimyosin uptake was quantified by a heart-to-lung ratio. All patients had absent antimyosin uptake (mean ratio 1.40 {+-} 0.06) with normal MIBG uptake (ratio 1.85 {+-} 0.29) before chemotherapy; ejection fraction was 61% {+-} 8%. With a 240-300 mg/m{sup 2} dose of doxorubicin, an increase in antimyosin uptake was observed with a ratio of 1.85 {+-} 0.2 (p < 0.01), whereas a similar degree of MIBG uptake was observed (mean ratio of 1.80 {+-} 0.2, p = ns); ejection fraction was 59% {+-} 5% (p = ns). At 420-600 mg/m{sup 2}, increased antimyosin uptake was observed with a ratio of 2.02 {+-} 0.3 (p < 0.01), and a decrease in MIBG uptake was also observed (mean ratio of 1.76 {+-} 0.2, p < 0.05); ejection fraction was 52% {+-} 8% (p < 0.05). Patients with more intense antimyosin uptake at intermediate doses tended to be those with more severe functional impairment at maximal cumulative doses. At cumulative doses of 420-600 mg/m{sup 2}, antimyosin and MIBG studies detect cell damage and impaired adrenergic neuron activity in patients with maintained or slightly decreased ejection fraction. 33 refs., 3 figs., 2 tabs.

  20. In Vitro and In Vivo Evaluation of 89Zr-DS-8273a as a Theranostic for Anti-Death Receptor 5 Therapy

    PubMed Central

    Burvenich, Ingrid J.G.; Lee, Fook-Thean; Guo, Nancy; Gan, Hui K.; Rigopoulos, Angela; Parslow, Adam C.; O'Keefe, Graeme J.; Gong, Sylvia J.; Tochon-Danguy, Henri; Rudd, Stacey E.; Donnelly, Paul S.; Kotsuma, Masakatsu; Ohtsuka, Toshiaki; Senaldi, Giorgio; Scott, Andrew M.

    2016-01-01

    Background: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro. In vivo biodistribution and pharmacokinetic studies were performed, including SPECT/CT and PET/MR imaging. A dose-escalation study using a PET/MR imaging quantitative analysis was also performed to determine DR5 receptor saturability in a mouse model. Results: 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a showed high immunoreactivity (100%), high serum stability, and bound to DR5 expressing cells with high affinity (Ka, 1.02-1.22 × 1010 M-1). The number of antibodies bound per cell was 32,000. In vivo biodistribution studies showed high and specific uptake of 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a in DR5 expressing COLO205 xenografts, with no specific uptake in normal tissues or in DR5-negative CT26 xenografts. DR5 receptor saturation was observed in vivo by biodistribution studies and quantitative PET/MRI analysis. Conclusion: 89Zr-Df-Bz-NCS-DS-8273a is a potential novel PET imaging reagent for human bioimaging trials, and can be used for effective dose assessment and patient response evaluation in clinical trials. PMID:27924159

  1. Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

    SciTech Connect

    Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L. )

    1990-06-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively.

  2. Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole

    SciTech Connect

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

    1986-02-01

    Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 (/sup 111/In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood /sup 111/In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts.

  3. Validation of a mutant of the pore-forming toxin sticholysin-I for the construction of proteinase-activated immunotoxins.

    PubMed

    Pentón, David; Pérez-Barzaga, Victor; Díaz, Iscel; Reytor, Mey L; Campos, Javier; Fando, Rafael; Calvo, Loany; Cilli, Eduardo M; Morera, Vivian; Castellanos-Serra, Lila R; Pazos, Fabiola; Lanio, María E; Alvarez, Carlos; Pons, Tirso; Tejuca, Mayra

    2011-06-01

    The use of pore-forming toxins from sea anemones (actinoporins) in the construction of immunotoxins (ITs) against tumour cells is an alternative for cancer therapy. However, the main disadvantage of actinoporin-based ITs obtained so far has been the poor cellular specificity associated with the toxin's ability to bind and exert its activity in almost any cell membrane. Our final goal is the construction of tumour proteinase-activated ITs using a cysteine mutant at the membrane binding region of sticholysin-I (StI), a cytolysin isolated from the sea anemone Stichodactyla helianthus. The mutant and the ligand moiety would be linked by proteinase-sensitive peptides through the StI cysteine residue blocking the toxin binding region and hence the IT non-specific killing activity. To accomplish this objective the first step was to obtain the mutant StI W111C, and to evaluate the impact of mutating tryptophan 111 by cysteine on the toxin pore-forming capacity. After proteolysis of the cleavage sequence, a short peptide would remain attached to the toxin. The next step was to evaluate whether this mutant is able to form pores even with a residual peptide linked to cysteine 111. In this work we demonstrated that (i) StI W111C shows pore-forming capacity in a nanomolar range, although it is 8-fold less active than the wild-type recombinant StI, corroborating the previously reported importance of residue 111 for the binding of StI to membranes, and (ii) the mutant is able to form pores even with a residual seven-residue peptide linked to cysteine 111. In addition, it was demonstrated that binding of a large molecule to cysteine 111 renders an inactive toxin that is no longer able to bind to the membrane. These results validate the mutant StI W111C for its use in the construction of tumour proteinase-activated ITs.

  4. The structure of adsorbed bromide concurrent with the underpotential deposition (UPD) of Cu on Pt(111)

    NASA Astrophysics Data System (ADS)

    Marković, Nenad M.; Lucas, Chris A.; Gasteiger, Hubert A.; Ross, Philip N.

    1997-02-01

    The adsorption of bromide anions concurrent with the underpotential deposition (UPD) of Cu on Pt(111) was examined utilizing ex-situ LEED and in-situ surface X-ray scattering for structure determination, in combination with coverage determination by rotating ring disk flux measurements with the Pt(111) single crystal as the disk electrode. The results show definitively that Cu UPD on Pt(111) in the presence of bromide is a two-step process, with the total amount of Cu deposited at underpotentials ˜0.95 ± 5% ML (1 ML = 1 adatom per Pt atom). The results also indicate that the surface coverage by adsorbed bromide undergoes only a small (<0.05 ML) change upon the deposition of Cu, even up to a nominal monolayer. We propose a model wherein the first stage of deposition occurs by displacement of the close-packed hexagonal layer of Br adatoms by Cu adatoms through a "turn-over" process, in which Cu is sandwiched between the Pt surface and the Br overlayer, leading to the formation of an ordered Pt(111)CuBr bilayer intermediate phase which closely resembles the (111) planes of the Cu(I)Br crystal. The coverage of both Cu and Br in this intermediate phase is ˜0.5 ML. The second stage is the filling-in of the Cu plane of the bilayer to form a pseudomorphic (1 × 1) Cu monolayer and a disordered Br adlayer with a coverage of ˜0.4 ML. The same mechanism is suggested for Cu UPD on Pt(111) in solutions containing chloride anions.

  5. Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs

    SciTech Connect

    Fischman, A.J.; Pike, M.C.; Kroon, D.; Fucello, A.J.; Rexinger, D.; ten Kate, C.; Wilkinson, R.; Rubin, R.H.; Strauss, H.W. )

    1991-03-01

    Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

  6. Radioimmunotherapy: Development of an effective approach

    SciTech Connect

    DeNardo, S.J.

    1991-01-01

    We plan to extend our success in treating B cell malignancies with {sup 131}I labeled Lym-1 by a major effort in therapy with {sup 67}Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the {sup 111}In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the {sup 111}In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N{prime},N{double prime}, N{prime}{double prime}-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of {sup 67}Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry.

  7. Radioimmunotherapy: Development of an effective approach. Annual report, 1991

    SciTech Connect

    DeNardo, S.J.

    1991-12-31

    We plan to extend our success in treating B cell malignancies with {sup 131}I labeled Lym-1 by a major effort in therapy with {sup 67}Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the {sup 111}In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the {sup 111}In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N{prime},N{double_prime}, N{prime}{double_prime}-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of {sup 67}Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry.

  8. Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.

    PubMed

    de Lorgeril, M; Rousseau, G; Basmadjian, A; St-Jean, G; Tran, D C; Latour, J G

    1990-01-01

    To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

  9. Influence of chelator and near-infrared dye labeling on biocharacteristics of dual-labeled trastuzumab-based imaging agents

    PubMed Central

    Aldrich, Melissa B; Yang, Zhi; Zhou, Nina; Xie, Qing; Liu, Chen; Sevick-Muraca, Eva

    2016-01-01

    Objective To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111In- (DTPA)n-trastuzumab-(IRDye 800)m. Methods Trastuzumab-based conjugates were synthesized and conjugated with diethylenetriaminepentaacetic acid (DTPA) at molar ratios of 1, 2, 3 and 5 and with a fluorescent dye (IRDye 800CW) at molar ratios of 1, 3 and 5. Immunoreactivity and internalization were assessed on SKBR-3 cells, overexpressing human epidermal growth factor receptor 2. The stability in human serum and phosphate-buffered saline (PBS) was evaluated. The biodistribution of dual-labeled conjugates was compared with that of 111In-(DTPA)2-trastuzumab in a SKBR-3 xenograft model to evaluate the effect of dye-to-protein ratio. Results All trastuzumab-based conjugates exhibited a high level of chemical and optical purity. Flow cytometry results showed that increasing dye-to-protein ratios were associated with decreased immunoreactivity. Stability studies revealed that the conjugate was stable in PBS, while in human serum, increased degradation and protein precipitation were observed with increasing dye-to-protein ratios. At 4 h, the percentages of internalization of dual-labeled conjugates normalized by dye-to-protein ratio (m) were 24.88%±2.10%, 19.99%±0.59%, and 17.47%±1.26% for "m" equal to 1, 3, and 5, respectively. A biodistribution study revealed a progressive decrease in tumor uptake with an increase in the dye-to-protein ratios. The liver, spleen and kidney showed a marked uptake with increased dye-to-protein ratios, particularly in the latter. Conclusions With non-specific-site conjugation of the fluorescent dye with a protein based on imaging agent, the increase in dye-to-protein ratios negatively impacted the immunoreactivity and stability, indicating a reduced tumor uptake. PMID:27478322

  10. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    NASA Astrophysics Data System (ADS)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  11. Intraperitoneal immunoconjugates

    SciTech Connect

    Griffin, T.W.; Collins, J.; Bokhari, F.; Stochl, M.; Brill, A.B.; Ito, T.; Emond, G.; Sands, H. )

    1990-02-01

    Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing.

  12. Molecular docking study of the binding of aminopyridines within the K+ channel.

    PubMed

    Caballero, Norma Angélica; Meléndez, Francisco Javier; Niño, Alfonso; Muñoz-Caro, Camelia

    2007-05-01

    We present a molecular docking study aimed to identify the binding site of protonated aminopyridines for the blocking of voltage dependent K(+) channels. Several active aminopyridines are considered: 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, 3,4-diaminopyridine, and 4-aminoquinoleine. We apply the AutoDock force field with a lamarckian genetic algorithm, using atomic charges for the ligands derived from the electrostatic potential obtained at the B3LYP/cc-pVDZ level. We find a zone in the alpha-subunit of the K(+) channel bearing common binding sites. This zone corresponds to five amino acids comprised between residuals Thr107 and Ala111, in the KcsA K(+) channel (1J95 pdb structure). The 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4-diaminopyridine bind to the carboxylic oxygens of Thr107 and Ala111. In all cases aminopyridines are perpendicular to the axis of the pore. 4-aminoquinoleine binds to the carboxylic oxygen of Ala111. Due to its large size, the molecular plane is parallel to the axis of the pore. The charge distributions and the structures of the binding complexes suggest that the interaction is driven by formation of several hydrogen bonds. We find 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4-diaminopyridine with similar binding energy. Considering the standard error of the estimate of the AutoDock force field, this energy should lie, as a rough estimation, in the interval 3-7 kcal mol(-1). On the other hand, 4-aminoquinoleine seems to have a smaller binding energy.

  13. Self-assembling behavior of glycerol monoundecenoate in water.

    PubMed

    Nyame Mendendy Boussambe, Gildas; Valentin, Romain; Fabre, Jean-François; Navailles, Laurence; Nallet, Frédéric; Gaillard, Cedric; Mouloungui, Zephirin

    2017-03-14

    Self-assembling properties of glycerol esters in water are well known. Still, few data on glyc-erol monoesters of undecylenic acid are available. The aim of this study was to highlight the behavior of the glycerol monoundecenoate (GM-C11:1) in different, diluted and concentrated states. Self-assembling properties in water and upon solid inorganic surfaces were investigated in diluted state with surface tension experiments, AFM and Cryo-TEM studies. In concen-trated state, the gelling properties in presence of water were investigated by polarized light microscopy, DSC and SAXS experiments. GM-C11:1 at 100 mg/L self-assembles at the liq-uid/air interfaces as aggregates of about 20 nm in diameter, organized into concentric forms. These aggregates were spherical globules composed of several molecules of GM-C11:1. At higher concentrations (1000 mg/L and 104 mg/L), GM-C11:1 was able to coat uniformly liq-uid/air and liquid/solid interfaces. In bulk GM-C11:1 form spontaneously aggregates and ves-icles. In more concentrated state, GM-C11:1 assembles into lamellar Lβ and Lα form in water. By cross-referencing SAXS and DSC findings, we were able to distinguish between interla-mellar water molecules strongly bound to GM-C11:1 and other molecules remaining unbound and considered as "mobile" water. The percentage of water strongly bound was proportional to the percentage of GM-C11:1 in the system. In this case, GM-C11:1 appears to be an effec-tive molecule for surface treatments for which water retention is important.

  14. Atomic jump frequencies in intermetallic compounds studied using perturbed angular correlation of gamma rays

    NASA Astrophysics Data System (ADS)

    Newhouse, Randal Leslie

    Atomic jump frequencies were determined in a variety of intermetallic compounds through analysis of nuclear relaxation of spectra measured using the nuclear hyperfine technique, perturbed angular correlation (PAC) of gamma rays. Observed at higher temperatures, this relaxation is attributed to fluctuations in the orientation or magnitude of electric field gradients (EFG) at nuclei of 111In/Cd probe atoms as the atoms make diffusive jumps. Jump frequencies were obtained by fitting dynamically relaxed PAC spectra using either an empirical relaxation function or using ab initio relaxation models created using the program PolyPacFit. Jump frequency activation enthalpies were determined from measurements over a range of temperatures. Diffusion was studied in the following systems: 1) Pseudo-binary alloys having the L12 crystal structure such as In3(La1-xPrx). The goal was to see how jump frequencies were affected by random disorder. 2) The family of layered phases, LanCoIn3n+2 ( n=0,1,2,3…∞). The goal was to see how jump frequencies varied with the spacing of Co layers, which were found to block diffusion. 3) Phases having the FeGa3 structure. The goal was to analyze dynamical relaxation for probe atoms having multiple inequivalent jump vectors. 4) Phases having the tetragonal Al4Ba structure. The goal was to search for effects in the PAC spectra caused by fluctuations in magnitudes of EFGs without fluctuations in orientations. Ab initio relaxation models were developed to simulate and fit dynamical relaxation for PAC spectra of FeGa3, and several phases with the Al4Ba structure in order to determine underlying microscopic jump frequencies. In the course of this work, site preferences also were observed for 111In/Cd probe atoms in several FeGa 3 and Al4Ba phases.

  15. Radiopharmaceuticals for somatostatin receptor imaging.

    PubMed

    Mikołajczak, Renata; Maecke, Helmut R

    2016-01-01

    The aim of this review is to summarize the developments and briefly characterize the somatostatin analogs which are currently used for somatostatin receptor imaging in clinical routine or in early phase clinical trials. Somatostatin (sst) receptor targeting with radiolabeled peptides has become an integral part in nuclear oncology during the last 20 years. This integration process has been initiated in Europe with the introduction to the market of 111In-DTPA-DPhe1-octreotide [111In-pentetreotide]. Introducing 99mTc in somatostatin receptor targeting radiopeptides resulted in much better image quality, higher sensitivity of tumor detection and lower mean effective dose for the examined patient. The next generation are 68Ga labeled somatostatin analogs. Due to the spatial resolution of PET technique and increasing number of PET scanners, the PET or PET/CT technique became very important in somatostatin receptor imaging. Until up to a couple of years ago the analogs of somatostatin were constructed aiming at their agonistic behavior, expecting that their internalization with the receptor acti-vated by the radiolabeled ligand and its retention within the tumor cell are crucial for efficient imaging and therapy. Recently it has been shown that the antagonists recognize more binding sites at the tumor cell membrane and hence offer an improved diagnostic efficacy, especially when the density of sst receptors is low. This approach may in future improve diagnostic value of somatostatin receptor imaging techniques. The developments in tracer design are followed by the improvements in imaging techniques. The new SPECT scanners offer resolution close to that of PET, which might open a new era for 99mTc and other SPECT radiotracers.

  16. Evaluation of ¹¹¹In-Labelled Exendin-4 Derivatives Containing Different Meprin β-Specific Cleavable Linkers

    PubMed Central

    Jodal, Andreas; Pape, Fabienne; Becker-Pauly, Christoph; Maas, Ole; Schibli, Roger; Béhé, Martin

    2015-01-01

    Background Cleavable linkers, which are specifically cleaved by defined conditions or enzymes, are powerful tools that can be used for various purposes. Amongst other things, they have been successfully used to deliver toxic payloads as prodrugs into target tissues. In this work novel linker sequences targeting meprin β, a metalloprotease expressed in the kidney brush-border membrane, were designed and included in the sequence of three radiolabelled exendin-4 derivatives. As radiolabelled exendin-4 derivatives strongly accumulate in the kidneys, we hypothesised that specific cleavage of the radiolabelled moiety at the kidney brush-border membrane would allow easier excretion of the activity into the urine and therefore improve the pharmacological properties of the peptide. Results The insertion of a cleavable linker did not negatively influence the in vitro properties of the peptides. They showed a good affinity to the GLP-1 receptor expressed in CHL cells, a high internalisation and sufficiently high stability in fresh human blood plasma. In vitro digestion with recombinant meprin β rapidly metabolised the corresponding linker sequences. After 60 min the majority of the corresponding peptides were digested and at the same time the anticipated fragments were formed. The peptides were also quickly metabolised in CD1 nu/nu mouse kidney homogenates. Immunofluorescence staining of meprin β in kidney sections confirmed the expression of the protease in the kidney brush-border membrane. Biodistribution in GLP-1 receptor positive tumour-xenograft bearing mice revealed high specific uptake of the 111In-labelled tracers in receptor positive tissue. Accumulation in the kidneys, however, was still high and comparable to the lead compound 111In-Ex4NOD40. Conclusion In conclusion, we show that the concept of cleavable linkers specific for meprin β is feasible, as the peptides are rapidly cleaved by the enzyme while retaining their biological properties. PMID:25855967

  17. Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart.

    PubMed Central

    Montrucchio, G.; Alloatti, G.; Mariano, F.; Comino, A.; Cacace, G.; Polloni, R.; De Filippi, P. G.; Emanuelli, G.; Camussi, G.

    1993-01-01

    This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury. Images Figure 5 Figure 6 PMID:8434642

  18. Choice of labeling and cell line influences interactions between the Fab fragment AbD15179 and its target antigen CD44v6.

    PubMed

    Stenberg, Jonas; Spiegelberg, Diana; Karlsson, Hampus; Nestor, Marika

    2014-02-01

    Medical imaging by use of immunotargeting generally relies on a labeled molecule binding to a specific target on the cell surface. It is important to utilize both cell-based and time-resolved binding assays in order to understand the properties of such molecular interactions in a relevant setting. In this report we describe the detailed characterization of the interaction properties for AbD15179, a promising CD44v6-targeting antibody fragment for radio-immunotargeting. Influence of labeling and cell-line model on the protein interaction kinetics was assessed using three different labeling approaches ((111)In, (125)I and FITC) on three different squamous carcinoma cell lines. Interactions were measured using time-resolved assays on living cells, and further analyzed with Interaction Map®. Results demonstrated a general biphasic appearance of a high- and a low-affinity binding event in all cases. The relative contribution from these two interactions differed between conjugates. For (125)I-Fab, the population of low-affinity binders could be significantly increased by extending the chloramine T exposure during labeling, whereas the (111)In-labeling predominantly resulted in a high-affinity interaction. Interactions were also shown to be cell line dependent, with e.g. SCC-25 cells generally mediating a faster dissociation of conjugates compared to the other cell lines. In conclusion, we report both cell line dependent and labeling associated variations in interaction kinetics for AbD15179 binding to CD44v6. This has implications for cell-based kinetic assays and applications based on labeled conjugates in general, as well as in a clinical setting, where each individual tumor may create different kinetic profiles for the same conjugate.

  19. Coregistration of magnetic resonance and single photon emission computed tomography images for noninvasive localization of stem cells grafted in the infarcted rat myocardium.

    PubMed

    Shen, Dinggang; Liu, Dengfeng; Cao, Zixiong; Acton, Paul D; Zhou, Rong

    2007-01-01

    This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82 degrees , respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with (111)Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of (111)In-labeled stem cells and of [(99m)Tc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the (111)In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image.

  20. Isolation and Characterization of Carbendazim-degrading Rhodococcus erythropolis djl-11

    PubMed Central

    Harvey, Paul R.; Li, Hongmei; Ren, Yan; Li, Jishun; Wang, Jianing; Yang, Hetong

    2013-01-01

    Carbendazim (methyl 1H-benzimidazol-2-yl carbamate) is one of the most widely used fungicides in agriculture worldwide, but has been reported to have adverse effects on animal health and ecosystem function. A highly efficient carbendazim-degrading bacterium (strain dj1-11) was isolated from carbendazim-contaminated soil samples via enrichment culture. Strain dj1-11 was identified as Rhodococcus erythropolis based on morphological, physiological and biochemical characters, including sequence analysis of the 16S rRNA gene. In vitro degradation of carbendazim (1000 mg·L−1) by dj1-11 in minimal salts medium (MSM) was highly efficient, and with an average degradation rate of 333.33 mg·L−1·d−1 at 28°C. The optimal temperature range for carbendazim degradation by dj1-11 in MSM was 25–30°C. Whilst strain dj1-11 was capable of metabolizing cabendazim as the sole source of carbon and nitrogen, degradation was significantly (P<0.05) increased by addition of 12.5 mM NH4NO3. Changes in MSM pH (4–9), substitution of NH4NO3 with organic substrates as N and C sources or replacing Mg2+ with Mn2+, Zn2+ or Fe2+ did not significantly affect carbendazim degradation by dj1-11. During the degradation process, liquid chromatography-mass spectrometry (LC-MS) detected the metabolites 2-aminobenzimidazole and 2-hydroxybenzimidazole. A putative carbendazim-hydrolyzing esterase gene was cloned from chromosomal DNA of djl-11 and showed 99% sequence homology to the mheI carbendazim-hydrolyzing esterase gene from Nocardioides sp. SG-4G. PMID:24098350

  1. Miniaturized antibodies for imaging membrane type-1 matrix metalloproteinase in cancers.

    PubMed

    Kondo, Naoya; Temma, Takashi; Shimizu, Yoichi; Watanabe, Hiroyuki; Higano, Keiichi; Takagi, Yoko; Ono, Masahiro; Saji, Hideo

    2013-04-01

    Since membrane type-1 matrix metalloproteinase (MT1-MMP) plays pivotal roles in tumor progression and metastasis and holds great promise as an early biomarker for malignant tumors, a method of evaluating MT1-MMP expression levels would be valuable for molecular biological and clinical studies. Although we have previously developed a (99m) Tc-labeled anti-MT1-MMP monoclonal IgG ((99m) Tc-MT1-mAb) as an MT1-MMP imaging probe by nuclear medical techniques for this purpose, slow pharmacokinetics were a problem due to its large molecular size. Thus, in this study, our aim was to develop miniaturized antibodies, a single chain antibody fragment (MT1-scFv) and a dimer of two molecules of scFv (MT1-diabody), as the basic structures of MT1-MMP imaging probes followed by in vitro and in vivo evaluation with an (111) In radiolabel. Phage display screening successfully provided MT1-scFv and MT1-diabody, which had sufficiently high affinity for MT1-MMP (KD  = 29.8 and 17.1 nM). Both (111) In labeled miniaturized antibodies showed higher uptake in MT1-MMP expressing HT1080 cells than in non-expressing MCF7 cells. An in vivo biodistribution study showed rapid pharmacokinetics for both probes, which exhibited >20-fold higher tumor to blood radioactivity ratios (T/B ratio), an index for in vivo imaging, than (99m) Tc-MT1-mAb 6 h post-administration, and significantly higher tumor accumulation in HT1080 than MCF7 cells. SPECT images showed heterogeneous distribution and ex vivo autoradiographic analysis revealed that the radioactivity distribution profiles in tumors corresponded to MT1-MMP-positive areas. These findings suggest that the newly developed miniaturized antibodies are promising probes for detection of MT1-MMP in cancer cells.

  2. Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent

    PubMed Central

    Chatalic, Kristell L.S.; Heskamp, Sandra; Konijnenberg, Mark; Molkenboer-Kuenen, Janneke D.M.; Franssen, Gerben M.; Clahsen-van Groningen, Marian C.; Schottelius, Margret; Wester, Hans-Jürgen; van Weerden, Wytske M.; Boerman, Otto C.; de Jong, Marion

    2016-01-01

    Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics—they rapidly and efficiently localize in tumor lesions. However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications. Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. 111In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands. Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of 111In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA. SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs. Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during 177Lu-PSMA I&T radionuclide therapy. Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy. Mice injected with 177Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with 177Lu-PSMA I&T + 2-PMPA did not. These data indicate that PSMA I&T is a promising theranostic tool for PCa. PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA. PMID:27162555

  3. Synthesis of polyglutamide-based metal-chelating polymers and their site-specific conjugation to trastuzumab for auger electron radioimmunotherapy.

    PubMed

    Lu, Yijie; Ngo Ndjock Mbong, Ghislaine; Liu, Peng; Chan, Conrad; Cai, Zhongli; Weinrich, Dirk; Boyle, Amanda J; Reilly, Raymond M; Winnik, Mitchell A

    2014-06-09

    Three types of metal-chelating polymers (MCPs) with hydrazide end groups were synthesized. (1) The first set of polymers (the F-series) was synthesized with a furan end group, and all of the pendant groups along the chain carried only a diethylenetriaminepentaacetic acid (DTPA) metal-chelating functionality. The hydrazide was introduced via a Diels-Alder reaction between the furan and 3,3'-N-[ε-maleimidocaproic acid] hydrazide (EMCH). (2) The P-series polymers was designed to carry several copies of a nuclear-localization peptide sequence (NLS peptides, CGYGPKKKRKVGG, harboring the NLS from the simian virus 40 large T-antigen) in addition to the DTPA metal-chelating groups. (3) The third type of polymer (the P-Py series) was a variation of the P-series polymers but with the introduction of a small number of pyrene chromophores along the backbone to allow for UV measurement of the incorporation of the MCPs into trastuzumab (tmab). These hydrazide-terminated polymers were site-specifically conjugated to aldehyde groups generated by NaIO4 oxidation of the pendant glycan in the Fc domain of tmab. The immunoconjugates were radiolabeled with (111)In and analyzed by SE-HPLC to confirm the attachment of the polymer to the antibody. HER2 binding assays demonstrated that neither the MCPs nor the presence of the NLS peptides interfered with specific antigen recognition on SK-Br-3 cells, although nonspecific binding was increased by polymer conjugation. Our results suggest that MCPs can be site-specifically attached to antibodies via oxidized glycans in the Fc domain and labeled with (111)In to construct radioimmunoconjugates with preserved immunoreactivity.

  4. Differential presentation of tumor antigen-derived epitopes by MHC-class I and antigen-positive tumor cells.

    PubMed

    Held, Gerhard; Neumann, Frank; Sturm, Christine; Kaestner, Lars; Dauth, Nina; de Bruijn, Diederik R; Renner, Christoph; Lipp, Peter; Pfreundschuh, Michael

    2008-10-15

    SSX2 is a member of the family of cancer/testis antigens. The SSX2 derived peptide SSX2(103-111) has been shown to be presented to cytotoxic T-lymphocytes (CTL) by Major-Histocompatibility (MHC) Class-I complexes after endogenous processing, more precisely by the allele HLA-A*0201. The HLA-A*0201- and SSX2-positive melanoma cell line SK-Mel-37 but not Me275 had been shown to elicit reactivity in SSX2(103-111) specific cytotoxic T-lymphocytes. To analyze the correlation between SSX2(103-111) presentation and T-cell stimulation, we intended to visualize presentation of SSX2(103-111) in these melanoma cell lines. Fab-antibodies were established from a human phage library with specificity for SSX2(103-111)/HLA-A*0201 complexes (but non-reactive with HLA-A*0201 or SSX2(103-111) alone) and used to visualize the presentation of SSX2(103-111) in the context of HLA-A*0201 by fluorescence microscopy. Presentation of SSX2(103-111) the context of HLA-A*0201 was demonstrated for the majority of SK-Mel-37, but for only a small fraction (<1%) of Me275 as indicated by a clear membrane-staining pattern in fluorescence microscopy. The presentation of SSX2(103-111) on SK-Mel37 and Me275, but not the expression of the SSX2 protein correlated with the capability of these cells to stimulate cells of an SSX2(103-111)-specific T-cell clone. MHC-peptide specific antibodies are a valuable tool for the analysis of antigenic peptides in the context of MHC-I molecules and for the structural definition of immunodominant epitopes.

  5. Diagnosis and management of the infected total joint arthroplasty

    SciTech Connect

    Cuckler, J.M.; Star, A.M.; Alavi, A.; Noto, R.B. )

    1991-07-01

    The preoperative diagnosis of the infected orthopedic implant is complicated by lack of a single precise test to forewarn patient and surgeon of the presence of microorganisms. Given the overall limitation of accuracy of preoperative diagnosis to approximately 80% when 111In scanning, preoperative aspiration, and ESR are considered, it would seem prudent to approach each revision surgery with the possibility in mind of subclinical sepsis as the cause for failure of the implant. The essentials of surgical technique including thorough debridement of the wound and removal of all existing foreign bodies, especially including PMMA bone cement, are critical to minimizing the risk for occurrence or persistence of sepsis. Although the use of antibiotic impregnated bone cement may enhance the treatment of orthopedic sepsis, the data available to date lead to the conclusion that two-stage revision surgery in the face of known sepsis remains the cornerstone of surgical therapy for the infected implant, along with aggressive and rational antibiotic treatment. The surgeon is offered the following guidelines in the management of the septic total hip arthroplasty. 1. Preoperative evaluation including ESR, 111In WBC scan, and aspiration for culture and sensitivity (fluoroscopically guided for the hip) will produce on average approximately 80% accuracy. 2. Intraoperative cultures at the time of revision surgery should be obtained prior to administration of systemic antibiotics; three tissue specimens (hip capsule, femoral membrane, acetabular membrane) should be submitted for culture and sensitivity determination. 3. Careful debridement of the surgical site of granulation tissue and all foreign bodies (e.g., PMMA) should be performed within the limits of patient safety to maximize the likelihood of success. 37 refs.

  6. Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics

    PubMed Central

    Buckle, Tessa; van der Wal, Steffen; van Malderen, Stijn J.M.; Müller, Larissa; Kuil, Joeri; van Unen, Vincent; Peters, Ruud J.B.; van Bemmel, Margaretha E.M.; McDonnell, Liam A.; Velders, Aldrik H.; Koning, Frits; Vanhaeke, Frank; van Leeuwen, Fijs W. B.

    2017-01-01

    Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the

  7. Metal-Chelating Polymers (MCPs) with Zwitterionic Pendant Groups Complexed to Trastuzumab Exhibit Decreased Liver Accumulation Compared to Polyanionic MCP Immunoconjugates.

    PubMed

    Liu, Peng; Boyle, Amanda J; Lu, Yijie; Adams, Jarrett; Chi, Yuechuan; Reilly, Raymond M; Winnik, Mitchell A

    2015-11-09

    Metal-chelating polymers (MCPs) can amplify the radioactivity delivered to cancer cells by monoclonal antibodies or their Fab fragments. We focus on trastuzumab (tmAb), which is used to target cancer cells that overexpress human epidermal growth factor receptor 2 (HER2). We report the synthesis and characterization of a biotin (Bi) end-capped MCP, Bi-PAm(DET-DTPA)36, a polyacrylamide with diethylenetriaminepentaacetic acid (DTPA) groups attached as monoamides to the polymer backbone by diethylenetriamine (DET) pendant groups. We compared its behavior in vivo and in vitro to a similar MCP with ethylenediamine (EDA) pendant groups (Bi-PAm(EDA-DTPA)40). These polymers were complexed to a streptavidin-modified Fab fragment of tmAb, then labeled with (111)In to specifically deliver multiple copies of (111)In to HER2+ cancer cells. Upon decay, (111)In emits γ-rays that can be used in single-photon emission computed tomography radioimaging, as well as Auger electrons that cause lethal double strand breakage of DNA. Our previous studies in Balb/c mice showed that radioimmunoconjugates (RICs) containing the Bi-PAm(EDA-DTPA)40 polymer had extremely short blood circulation time and high liver uptake and were, thus, unsuitable for in vivo studies. The polymer Bi-PAm(EDA-DTPA)40 carries negative charges on each pendant group at neutral pH and a net charge of (-1) on each pendant group when saturated with stable In(3+). To test our hypothesis that charge associated with the polymer repeat unit is a key factor affecting its biodistribution profile, we examined the biodistribution of RICs containing Bi-PAm(DET-DTPA)36. While this polymer is also negatively charged at neutral pH, it becomes a zwitterionic MCP upon saturation of the DTPA groups with stable In(3+) ions. In both nontumor bearing Balb/c mice and athymic mice implanted with HER2+ SKOV-3 human ovarian cancer tumors, we show that the zwitterionic MCP has improved biodistribution, higher blood levels of radioactivity

  8. Site-specific conjugation of monodispersed DOTA-PEGn to a thiolated diabody reveals the effect of increasing peg size on kidney clearance and tumor uptake with improved 64-copper PET imaging.

    PubMed

    Li, Lin; Crow, Desiree; Turatti, Fabio; Bading, James R; Anderson, Anne-Line; Poku, Erasmus; Yazaki, Paul J; Carmichael, Jenny; Leong, David; Wheatcroft, David; Wheatcroft, Michael P; Raubitschek, Andrew A; Hudson, Peter J; Colcher, David; Shively, John E

    2011-04-20

    Optimal PET imaging of tumors with radiolabeled engineered antibodies requires, among other parameters, matching blood clearance and tumor uptake with the half-life of the engineered antibody. Although diabodies have favorable molecular sizes (50 kDa) for rapid blood clearance (t(1/2) = 30-60 min) and are bivalent, thereby increasing tumor uptake, they exhibit substantial kidney uptake as their major route of clearance, which is especially evident when they are labeled with the PET isotope (64)Cu (t(1/2) = 12 h). To overcome this drawback, diabodies may be conjugated to PEG, a modification that increases the apparent molecular size of the diabody and reduces kidney uptake without adversely affecting tumor uptake or the tumor to blood ratio. We show here that site-specific attachment of monodispersed PEGn of increasing molecular size (n = 12, 24, and 48) can uniformly increase the apparent molecular size of the PEG-diabody conjugate, decrease kidney uptake, and increase tumor uptake, the latter due to the increased residence time of the conjugate in the blood. Since the monodispersed PEGs were preconjugated to the chelator DOTA, the conjugates were able to bind radiometals such as (111)In and (64)Cu that can be used for SPECT and PET imaging, respectively. To allow conjugation of the DOTA-PEG to the diabody, the DOTA-PEG incorporated a terminal cysteine conjugated to a vinyl sulfone moiety. In order to control the conjugation chemistry, we have engineered a surface thiolated diabody that incorporates two cysteines per monomer (four per diabody). The thiolated diabody was expressed and purified from bacterial fermentation and only needs to be reduced prior to conjugation to the DOTA-PEGn-Cys-VS. This novel imaging agent (a diabody with DOTA-PEG48-Cys-VS attached to introduced thiols) gave up to 80%ID/g of tumor uptake with a tumor to blood ratio (T/B) of 8 at 24 h when radiolabeled with (111)In and 37.9% ID/g of tumor uptake (T/B = 8) at 44 h when radiolabeled with

  9. Anion adsorption induced surface reconstructions

    NASA Astrophysics Data System (ADS)

    Tang, Lei

    2005-11-01

    Surface stress plays an important role in the behavior of solid surfaces. Potential-controlled anion adsorption in electrolytes alters the surface stress of the electrode and results in morphology changes to the surfaces. With a combination of potential-induced surface stress measurement and in situ electrochemical scanning tunneling microscopy (STM), it is demonstrated that anion adsorption induces changes in structure of thin films and modifies the growth morphology and stress evolution in epitaxially grown films. Surface structural transitions in the heteroepitaxial system consisting of one to two gold monolayers on platinum substrates were observed. By increasing the potential, structural transitions, from (1 x 1), to a striped phase, to a hexagonal structure, occurred in the gold bilayer. This hexagonal structure was related to the formation of an ordered sulfate adlayer with a ( 3x7 ) structure. Such transitions were repeatable by cycling the potential. Furthermore, the transitions between various dislocation structures were affected by anion adsorption. The surface composition of the gold bilayer on Pt was measured by underpotential deposition of copper. By subtracting the contribution of a pure Pt surface from the gold bi-layer on Pt, a stress change of -2.4 N/m was observed, which agrees with the stress change of -2.46 N/m predicted to accompany formation of 1.5 MLs of coherent Au on Pt(111) from epitaxy theory. The Cu monolayer deposited on Au(111) from an acid sulfate electrolyte was found to be pseudomorphic while the Cu monolayer formed on Au(111) in vacuum was incoherent. The stress-thickness change associated with the coherent monolayer of copper on Au(111) in electrolyte was -0.6 N/m, while conventional epitaxy theories predict a value of +7.76 N/m. STM results elucidated the sulfate adsorption on the copper monolayer caused an expansion of the layer as evidenced by a Moire Structure. For the Cu monolayer on Au(111), the sulfate-induced expansion

  10. Indium donor/metal vacancy defect complexes in cadmium telluride studied with perturbed angular correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Griffith, John Warren

    Semi-insulating, powder samples of Cadmium Telluride (CdTe) have been studied using 111In Time Differential Perturbed Angular Correlation (PAC) Spectroscopy. The samples have been lightly doped (˜10 12 cm-3) with 111In atoms, which occupy well-defined metal (Cd) lattice sites and act as probes of the local environment. These substitutional donors form a single defect complex in CdTe. This complex has been identified and characterized as a function of temperature. Those indium probes that are not complexed occupy metal lattice sites with no defect in the local vicinity. Samples containing metal vacancy concentrations as large as 500 ppm have been prepared by a high temperature anneal and quench. The defect complex involves the trapping of a cadmium metal vacancy bound to the indium probe. The electric field gradient (EFG) experienced by probe atoms has a coupling constant of nuQ = 61.5(5) MHz and is not axially symmetric, with the asymmetry parameter given by eta = 0.16(4). It is believed that this asymmetry results from a relaxation of the chalcogen (Te) atoms adjacent to the metal vacancy, with the tellurium atom shared by the probe atom and the vacancy providing the dominant contribution. The fraction of complexed probe atoms increases as the sample temperature is decreased, and is still increasing at room temperature. Complexed fractions are reproducible on cycling within the temperature range 40 to 200°C. The binding energy of the complex has been measured to be 0.15(2) eV and is independent of metal vacancy concentration, which varies and is dependent on the details of the quench. In rapidly cooled samples, a non-equilibrium number of these defect complexes is observed. This state equilibrates with a time constant of 45(5) hours at 15°C, implying that at least one of the two constituents involved in the complex has a significant diffusion rate at this temperature. Under the assumption that vacancy diffusion mechanisms dominate at this temperature, it is

  11. The biodistribution of gold nanoparticles designed for renal clearance

    NASA Astrophysics Data System (ADS)

    Alric, Christophe; Miladi, Imen; Kryza, David; Taleb, Jacqueline; Lux, François; Bazzi, Rana; Billotey, Claire; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2013-06-01

    Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions. However scintigraphy appears better suited for a biodistribution study owing to a great sensitivity. The successful immobilization of radioelements (99mTc, 111In) in the DTDTPA shell, instead of gadolinium ions, renders possible the follow up of Au@DTDTPA by scintigraphy which showed that Au@DTDTPA nanoparticles exhibit a safe behaviour after intravenous injection to healthy rats.Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate

  12. Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers.

    PubMed

    Yan, Heping; Kapoor, Vaishali; Nguyen, Kim; Akers, Walter J; Li, Hua; Scott, Jalen; Laforest, Richard; Rogers, Buck; Thotala, Dinesh; Hallahan, Dennis

    2016-07-12

    Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1.Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors.We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro.In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control.

  13. A dose point kernel database using GATE Monte Carlo simulation toolkit for nuclear medicine applications: Comparison with other Monte Carlo codes

    SciTech Connect

    Papadimitroulas, Panagiotis; Loudos, George; Nikiforidis, George C.; Kagadis, George C.

    2012-08-15

    Purpose: GATE is a Monte Carlo simulation toolkit based on the Geant4 package, widely used for many medical physics applications, including SPECT and PET image simulation and more recently CT image simulation and patient dosimetry. The purpose of the current study was to calculate dose point kernels (DPKs) using GATE, compare them against reference data, and finally produce a complete dataset of the total DPKs for the most commonly used radionuclides in nuclear medicine. Methods: Patient-specific absorbed dose calculations can be carried out using Monte Carlo simulations. The latest version of GATE extends its applications to Radiotherapy and Dosimetry. Comparison of the proposed method for the generation of DPKs was performed for (a) monoenergetic electron sources, with energies ranging from 10 keV to 10 MeV, (b) beta emitting isotopes, e.g., {sup 177}Lu, {sup 90}Y, and {sup 32}P, and (c) gamma emitting isotopes, e.g., {sup 111}In, {sup 131}I, {sup 125}I, and {sup 99m}Tc. Point isotropic sources were simulated at the center of a sphere phantom, and the absorbed dose was stored in concentric spherical shells around the source. Evaluation was performed with already published studies for different Monte Carlo codes namely MCNP, EGS, FLUKA, ETRAN, GEPTS, and PENELOPE. A complete dataset of total DPKs was generated for water (equivalent to soft tissue), bone, and lung. This dataset takes into account all the major components of radiation interactions for the selected isotopes, including the absorbed dose from emitted electrons, photons, and all secondary particles generated from the electromagnetic interactions. Results: GATE comparison provided reliable results in all cases (monoenergetic electrons, beta emitting isotopes, and photon emitting isotopes). The observed differences between GATE and other codes are less than 10% and comparable to the discrepancies observed among other packages. The produced DPKs are in very good agreement with the already published data

  14. Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers

    PubMed Central

    Yan, Heping; Kapoor, Vaishali; Nguyen, Kim; Akers, Walter J.; Li, Hua; Scott, Jalen; Laforest, Richard; Rogers, Buck; Thotala, Dinesh; Hallahan, Dennis

    2016-01-01

    Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1. Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors. We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro. In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control. PMID:27270318

  15. Utilizing the Multiradionuclide Resolving Power of SPECT and Dual Radiolabeled Single Molecules to Assess Treatment Response of Tumors

    PubMed Central

    Xu, Baogang; Shokeen, Monica; Sudlow, Gail P.; Harpstrite, Scott E.; Liang, Kexian; Cheney, Philip P.; Edwards, W. Barry; Sharma, Vijay; Laforest, Richard; Akers, Walter J.; Achilefu, Samuel

    2016-01-01

    Purpose Single photon emission computed tomography (SPECT) radionuclide pairs having distinct decay rates and different energy maxima enable simultaneous detection of dual gamma signals and real-time assessment of dynamic functional and molecular processes in vivo. Here, we report image acquisition and quantification protocols for a single molecule labeled with two different radionuclides for functional SPECT imaging. Procedures LS370 and LS734 were prepared using modular solid phase peptide synthesis. Each agent has a caspase-3 cleavable reporting motif, flanked by a tyrosine residue and a chelator at the opposite end of molecule. Cell uptake and efflux were assessed in human MDA-MB-231 breast cancer cells. Biodistribution studies were conducted in tumor naive and orthotopic 4T1 metastatic breast cancer tumor mice. NanoSPECT dual-imaging validation and attenuation correction parameters were developed using phantom vials containing varying radionuclide concentrations. Proof-of-principle SPECT imaging was performed in MMTV-PyMT transgenic mice. Results LS370 and LS734 were singly or dually radiolabeled with 125I and 111In or 99mTc. Cell assays demonstrated 11-fold higher percent uptake (P<0.001) of [125I]LS734 (3.6±0.5) compared to [125I]LS370 (0.3±0.3) at 2 h. Following chemotherapy, cellular retention of [125I]LS734 was 3-fold higher (P<0.05) than untreated cells. Pharmacokinetics at 1 h postinjection demonstrated longer blood retention (%ID/g) for [125I]LS734 (3.2±0.9) compared to [125I]LS370 (1.6±0.1). In mice bearing bilateral orthotopic 4T1 tumors, the uptake (%ID/g) was 2.4±0.3 for [125I]LS734 and 1.2±0.03 for [125I]LS370. The iodinated tyrosine peptide residue label was stable under in vitro conditions for up to 24 h; rapid systemic deiodination (high thyroid uptake) was observed in vivo. Phantom studies using standards demonstrated deconvolution of radionuclide signals based on different gamma ray energies. In MMTV-PyMT mice imaged with dual

  16. Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene

    PubMed Central

    Chen, Ron; Parry, Jesse J.; Akers, Walter J.; Berezin, Mikhail Y.; El Naqa, Issam M.; Achilefu, Samuel; Edwards, W. Barry; Rogers, Buck E.

    2010-01-01

    Gene therapy trials have traditionally used tumor and tissue biopsies for assessing the efficacy of gene transfer. Non-invasive imaging techniques offer a distinct advantage over tissue biopsies in that the magnitude and duration of gene transfer can be monitored repeatedly. Human somatostatin receptor subtype 2 (SSTR2) has been used for the nuclear imaging of gene transfer. To extend this concept, we have developed a somatostatin receptor–enhanced green fluorescent protein fusion construct (SSTR2-EGFP) for nuclear and fluorescent multimodality imaging. Methods An adenovirus containing SSTR2-EGFP (AdSSTR2-EGFP) was constructed and evaluated in vitro and in vivo. SCC-9 human squamous cell carcinoma cells were infected with AdEGFP, AdSSTR2, or AdSSTR2-EGFP for in vitro evaluation by saturation binding, internalization, and fluorescence spectroscopy assays. In vivo biodistribution and nano-SPECT imaging studies were conducted with mice bearing SCC-9 tumor xenografts directly injected with AdSSTR2-EGFP or AdSSTR2 to determine the tumor localization of 111In-diethylenetriaminepentaacetic acid (DTPA)-Tyr3-octreotate. Fluorescence imaging was conducted in vivo with mice receiving intratumoral injections of AdSSTR2, AdSSTR2-EGFP, or AdEGFP as well as ex vivo with tissues extracted from mice. Results The similarity between AdSSTR2-EGFP and wild-type AdSSTR2 was demonstrated in vitro by the saturation binding and internalization assays, and the fluorescence emission spectra of cells infected with AdSSTR2-EGFP was almost identical to the spectra of cells infected with wild-type AdEGFP. Biodistribution studies demonstrated that the tumor uptake of 111In-DTPA-Tyr3-octreotate was not significantly different (P > 0.05) when tumors (n = 5) were injected with AdSSTR2 or AdSSTR2-EGFP but was significantly greater than the uptake in control tumors. Fluorescence was observed in tumors injected with AdSSTR2-EGFP and AdEGFP in vivo and ex vivo but not in tumors injected with AdSSTR2

  17. [Investigation of radioactivity measurement of medical radioactive waste].

    PubMed

    Koizumi, Kiyoshi; Masuda, Kazutaka; Kusakabe, Kiyoko; Kinoshita, Fujimi; Kobayashi, Kazumi; Yamamoto, Tetsuo; Kanaya, Shinichi; Kida, Tetsuo; Yanagisawa, Masamichi; Iwanaga, Tetsuo; Ikebuchi, Hideharu; Kusama, Keiji; Namiki, Nobuo; Okuma, Hiroshi; Fujimura, Yoko; Horikoshi, Akiko; Tanaka, Mamoru

    2004-11-01

    To explore the possibility of which medical radioactive wastes could be disposed as general wastes after keeping them a certain period of time and confirming that their radioactivity reach a background level (BGL), we made a survey of these wastes in several nuclear medicine facilities. The radioactive wastes were collected for one week, packed in a box according to its half-life, and measured its radioactivity by scintillation survey meter with time. Some wastes could reach a BGL within 10 times of half-life, but 19% of the short half-life group (group 1) including 99mTc and 123I, and 8% of the middle half-life group (group 2) including 67Ga, (111)In, and 201Tl did not reach a BGL within 20 times of half-life. A reason for delaying the time of reaching a BGL might be partially attributed to high initial radiation dose rate or heavy package weight. However, mixing with the nuclides of longer half-life was estimated to be the biggest factor affecting this result. When disposing medical radioactive wastes as general wastes, it is necessary to avoid mixing with radionuclide of longer half-life and confirm that it reaches a BGL by actual measurement.

  18. Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa.

    PubMed

    Goole, J; Van Gansbeke, B; Pilcer, G; Deleuze, Ph; Blocklet, D; Goldman, S; Pandolfo, M; Vanderbist, F; Amighi, K

    2008-11-19

    In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers. Two concepts of sustained-release floating minitablets--Levo-Form 1 (matrix) and 2 (coated)--were evaluated and compared to the marketed product Prolopa HBS 125. All the floating forms were radiolabelled with (111)In in order to evaluate their gastric residence time using gamma-scintigraphy. It was shown that the three formulations offered almost the same mean gastric residence time, which was about 240 min. Prolopa HBS 125 and Levo-Form 2 presented intragastric disintegration, which can lead to a more pronounced "peak & valley" effect on the plasma concentration-time profile of levodopa. In contrast, the plasma concentration-time profile of levodopa following the administration of Levo-Form 1 was more evenly distributed. Moreover, Levo-Form 1 provided the lowest variations between men and women in terms of AUC and C(max) values. Finally, when the same amount of inhibitors of extracerebral dopa decarboxylase--carbidopa and benserazide--had been administrated, the mean AUC, C(max) and T(max) values obtained for benserazide were lower than those obtained for carbidopa.

  19. Socioeconomic status and length of hospital stay in children with vaso-occlusive crises of sickle cell disease.

    PubMed Central

    Ellison, Angela M.; Bauchner, Howard

    2007-01-01

    OBJECTIVE: To examine the association between socioeconomic status and length of hospital stay for vaso-occlusive crises in children with sickle cell disease. METHODS: 19,174 discharges (aged 1-20 years), with a primary diagnosis of sickle cell disease with crisis were analyzed from the Healthcare Cost and Utilization Project Kid Inpatient Database 2000. Socioeconomic status was assessed using an area-based measure, median household income by ZIP code and an individual-level measure, insurance status. We adjusted for age, gender, hospital location/teaching status, presence of pneumonia, number of diagnoses on record and number of procedures performed. Negative binomial regression models using generalized estimating equations (GEE) were used to assess length of stay. RESULTS: Socioeconomic status as measured by income was not associated with length of stay (incidence rate ratio (highest versus lowest category) = 1.04 (95% CI: 0.98, 1.11)). In contrast, socioeconomic status as measured by insurance was associated with length of stay [adjusted incidence rate ratio = 1.04 (95% CI: 1.01, 1.08)), although the magnitude of this difference is small and not likely to be clinically important. CONCLUSIONS: We found no evidence to suggest that socioeconomic status has any clinically important effect on length of hospital stay in children with vaso-occlusive crises in sickle cell disease. PMID:17393942

  20. Cyclopentenone derivatives and polyhydroxylated steroids from the soft coral Sinularia acuta.

    PubMed

    Zhang, Nai-Xia; Tang, Xu-Li; van Ofwegen, Leen; Xue, Lei; Song, Wen-Juan; Li, Ping-Lin; Li, Guo-Qiang

    2015-02-01

    Four new polyhydroxylated steroids, 1-4, and the racemic form of cyclopentenone 9, together with four known steroids, 5-8, one known cyclopentenone derivative, 10, and one known butenolide derivative, 11, were isolated from the soft coral Sinularia acuta collected from Weizhou Island of Guangxi Province, P. R. China. Their structures were elucidated on the basis of spectroscopic analyses and by comparison of the corresponding data with those previously reported. The cytotoxicities of the isolates 1-11 in vitro against the selected tumor cell lines HL-60, HeLa, and K562 were evaluated. Compounds 2 and 5 showed potent cytotoxicities against HL-60 cell lines with IC50 values of 7.3 and 9.9 μM, respectively. Compounds 5 and 6 showed moderate activities against K562 cell lines with IC50 values of 10.9 and 11.7 μM, respectively, while compounds 1, 2, and 6 showed weak activities against HeLa cell lines with respective IC50 values of 44.8, 27.1, and 18.2 μM. This is the first report on chemical and bioactivity research of S. acuta.

  1. Ultraviolet irradiation of platelet concentrates: Feasibility in transfusion practice

    SciTech Connect

    Andreu, G.; Boccaccio, C.; Lecrubier, C.; Fretault, J.; Coursaget, J.; LeGuen, J.P.; Oleggini, M.; Fournel, J.J.; Samama, M. )

    1990-06-01

    Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

  2. Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis

    SciTech Connect

    Johnson, R.J.; Alpers, C.E.; Pruchno, C.; Schulze, M.; Baker, P.J.; Pritzl, P.; Couser, W.G. )

    1989-11-01

    We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of {sup 111}In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

  3. Direct observation of adsorption geometry for the van der Waals adsorption of a single π-conjugated hydrocarbon molecule on Au(111)

    SciTech Connect

    Kim, Ju-Hyung; Jung, Jaehoon; Kim, Yousoo E-mail: ykim@riken.jp; Tahara, Kazukuni; Tobe, Yoshito E-mail: ykim@riken.jp; Kawai, Maki E-mail: ykim@riken.jp

    2014-02-21

    Weak van der Waals adsorption of π-conjugated hydrocarbon molecules onto the gold surface, Au(111), is one of the essential processes in constructing organic-metal interfaces in organic electronics. Here we provide a first direct observation of adsorption geometry of a single π-conjugated hydrocarbon molecule on Au(111) using an atomically resolved scanning tunneling microscopy study combined with van der Waals density functional methodology. For the purpose, we utilized a highly symmetric π-conjugated hydrocarbon molecule, dehydrobenzo[12]annulene (DBA), which has a definite three-fold symmetry, the same as the Au(111) surface. Interestingly, our observations on an atomically resolved scale clearly indicate that the DBA molecule has only one adsorption configuration on Au(111) in spite of the weak van der Waals adsorption system. Based on the precisely determined adsorption geometry of DBA/Au(111), our calculation results imply that even a very small contribution of the interfacial orbital interaction at the organic-metal interface can play a decisive role in constraining the adsorption geometry even in the van der Waals adsorption system of a π-conjugated hydrocarbon molecule on the noblest Au(111) surface. Our observations provide not only deeper insight into the weak adsorption process, but also new perspectives to organic electronics using π-conjugated hydrocarbon molecules on the Au surface.

  4. Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

    SciTech Connect

    Pollak, R.; Blanchard, J.M.; Lazda, V.A.

    1986-11-01

    Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs.

  5. Organometallic Bonding in an Ullmann-Type On-Surface Chemical Reaction Studied by High-Resolution Atomic Force Microscopy.

    PubMed

    Kawai, Shigeki; Sadeghi, Ali; Okamoto, Toshihiro; Mitsui, Chikahiko; Pawlak, Rémy; Meier, Tobias; Takeya, Jun; Goedecker, Stefan; Meyer, Ernst

    2016-10-01

    The on-surface Ullmann-type chemical reaction synthesizes polymers by linking carbons of adjacent molecules on solid surfaces. Although an organometallic compound is recently identified as the reaction intermediate, little is known about the detailed structure of the bonded organometallic species and its influence on the molecule and the reaction. Herein atomic force microscopy at low temperature is used to study the reaction with 3,9-diiododinaphtho[2,3-b:2',3'-d]thiophene (I-DNT-VW), which is polymerized on Ag(111) in vacuum. Thermally sublimated I-DNT-VW picks up a Ag surface atom, forming a CAg bond at one end after removing an iodine. The CAg bond is usually short-lived, and a CAgC organometallic bond immediately forms with an adjacent molecule. The existence of the bonded Ag atoms strongly affects the bending angle and adsorption height of the molecular unit. Density functional theory calculations reveal the bending mechanism, which reveals that charge from the terminus of the molecule is transferred via the Ag atom into the organometallic bond and strengths the local adsorption to the substrate. Such deformations vanish when the Ag atoms are removed by annealing and CC bonds are established.

  6. Using anti-poly(ethylene glycol) bioparticles for the quantitation of PEGylated nanoparticles.

    PubMed

    Hsieh, Yuan-Chin; Cheng, Ta-Chun; Wang, Hsin-Ell; Li, Jia-Je; Lin, Wen-Wei; Huang, Chien-Chiao; Chuang, Chih-Hung; Wang, Yeng-Tseng; Wang, Jaw-Yuan; Roffler, Steve R; Chuang, Kuo-Hsiang; Cheng, Tian-Lu

    2016-12-19

    Attachment of polyethylene glycol (PEG) molecules to nanoparticles (PEGylation) is a widely-used method to improve the stability, biocompatibility and half-life of nanomedicines. However, the evaluation of the PEGylated nanomedicine pharmacokinetics (PK) requires the decomposition of particles and purification of lead compounds before analysis by high performance liquid chromatography (HPLC), mass spectrometry, etc. Therefore, a method to directly quantify un-decomposed PEGylated nanoparticles is needed. In this study, we developed anti-PEG bioparticles and combined them with anti-PEG antibodies to generate a quantitative enzyme-linked immunosorbent assay (ELISA) for direct measurement of PEGylated nanoparticles without compound purification. The anti-PEG bioparticles quantitative ELISA directly quantify PEG-quantum dots (PEG-QD), PEG-stabilizing super-paramagnetic iron oxide (PEG-SPIO), Lipo-Dox and PEGASYS and the detection limits were 0.01 nM, 0.1 nM, 15.63 ng/mL and 0.48 ng/mL, respectively. Furthermore, this anti-PEG bioparticle-based ELISA tolerated samples containing up to 10% mouse or human serum. There was no significant difference in pharmacokinetic studies of radiolabeled PEG-nanoparticles (Nano-X-(111)In) through anti-PEG bioparticle-based ELISA and a traditional gamma counter. These results suggest that the anti-PEG bioparticle-based ELISA may provide a direct and effective method for the quantitation of any whole PEGylated nanoparticles without sample preparation.

  7. Using anti-poly(ethylene glycol) bioparticles for the quantitation of PEGylated nanoparticles

    PubMed Central

    Hsieh, Yuan-Chin; Cheng, Ta-Chun; Wang, Hsin-Ell; Li, Jia-Je; Lin, Wen-Wei; Huang, Chien-Chiao; Chuang, Chih-Hung; Wang, Yeng-Tseng; Wang, Jaw-Yuan; Roffler, Steve R.; Chuang, Kuo-Hsiang; Cheng, Tian-Lu

    2016-01-01

    Attachment of polyethylene glycol (PEG) molecules to nanoparticles (PEGylation) is a widely-used method to improve the stability, biocompatibility and half-life of nanomedicines. However, the evaluation of the PEGylated nanomedicine pharmacokinetics (PK) requires the decomposition of particles and purification of lead compounds before analysis by high performance liquid chromatography (HPLC), mass spectrometry, etc. Therefore, a method to directly quantify un-decomposed PEGylated nanoparticles is needed. In this study, we developed anti-PEG bioparticles and combined them with anti-PEG antibodies to generate a quantitative enzyme-linked immunosorbent assay (ELISA) for direct measurement of PEGylated nanoparticles without compound purification. The anti-PEG bioparticles quantitative ELISA directly quantify PEG-quantum dots (PEG-QD), PEG-stabilizing super-paramagnetic iron oxide (PEG-SPIO), Lipo-Dox and PEGASYS and the detection limits were 0.01 nM, 0.1 nM, 15.63 ng/mL and 0.48 ng/mL, respectively. Furthermore, this anti-PEG bioparticle-based ELISA tolerated samples containing up to 10% mouse or human serum. There was no significant difference in pharmacokinetic studies of radiolabeled PEG-nanoparticles (Nano-X-111In) through anti-PEG bioparticle-based ELISA and a traditional gamma counter. These results suggest that the anti-PEG bioparticle-based ELISA may provide a direct and effective method for the quantitation of any whole PEGylated nanoparticles without sample preparation. PMID:27991598

  8. Systematic theoretical study of ethylene adsorption on δ-MoC(001), TiC(001), and ZrC(001) surfaces

    DOE PAGES

    Jimenez-Orozco, Carlos; Florez, Elizabeth; Moreno, Andres; ...

    2016-05-31

    A systematic study of ethylene adsorption over δ-MoC(001), TiC(001), and ZrC(001) surfaces was conducted by means of calculations based on periodic density functional theory. The structure and electronic properties of each carbide pristine surface had a strong influence in the bonding of ethylene. It was found that the metal and carbon sites of the carbide could participate in the adsorption process. As a consequence of this, very different bonding mechanisms were seen on δ-MoC(001) and TiC(001). The bonding of the molecule on the TMC(001) systems showed only minor similarities to the type of bonding found on a typical metal likemore » Pt(111). In general, the ethylene binding energy follow the trend in stability: ZrC(001) < TiC(001) < δ-MoC(001) < Pt(111). The van der Waals correction to the energy produces large binding energy values, modifies the stability orders and drives the ethylene closer to the surface but the adsorbate geometry parameters remain unchanged. Ethylene was activated on clearly defined binding geometries, changing its hybridization from sp2 to sp3 with an elongation (0.16–0.31 Å) of the C=C bond. As a result, on the basis of this theoretical study, δ-MoC(001) is proposed as a potential catalyst for the hydrogenation of olefins, whereas TiC(001) could be useful for their hydrogenolysis.« less

  9. Systematic theoretical study of ethylene adsorption on δ-MoC(001), TiC(001), and ZrC(001) surfaces

    SciTech Connect

    Jimenez-Orozco, Carlos; Florez, Elizabeth; Moreno, Andres; Liu, Ping; Rodriguez, José A.

    2016-05-31

    A systematic study of ethylene adsorption over δ-MoC(001), TiC(001), and ZrC(001) surfaces was conducted by means of calculations based on periodic density functional theory. The structure and electronic properties of each carbide pristine surface had a strong influence in the bonding of ethylene. It was found that the metal and carbon sites of the carbide could participate in the adsorption process. As a consequence of this, very different bonding mechanisms were seen on δ-MoC(001) and TiC(001). The bonding of the molecule on the TMC(001) systems showed only minor similarities to the type of bonding found on a typical metal like Pt(111). In general, the ethylene binding energy follow the trend in stability: ZrC(001) < TiC(001) < δ-MoC(001) < Pt(111). The van der Waals correction to the energy produces large binding energy values, modifies the stability orders and drives the ethylene closer to the surface but the adsorbate geometry parameters remain unchanged. Ethylene was activated on clearly defined binding geometries, changing its hybridization from sp2 to sp3 with an elongation (0.16–0.31 Å) of the C=C bond. As a result, on the basis of this theoretical study, δ-MoC(001) is proposed as a potential catalyst for the hydrogenation of olefins, whereas TiC(001) could be useful for their hydrogenolysis.

  10. A quantitative method to measure human platelet chemotaxis using indium-111-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 conditons 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. Predicting kinetic nanocrystal shapes through multi-scale theory and simulation: Polyvinylpyrrolidone-mediated growth of Ag nanocrystals

    NASA Astrophysics Data System (ADS)

    Balankura, Tonnam; Qi, Xin; Zhou, Ya; Fichthorn, Kristen A.

    2016-10-01

    In the shape-controlled synthesis of colloidal Ag nanocrystals, structure-directing agents, particularly polyvinylpyrrolidone (PVP), are known to be a key additive in making nanostructures with well-defined shapes. Although many Ag nanocrystals have been successfully synthesized using PVP, the mechanism by which PVP actuates shape control remains elusive. Here, we present a multi-scale theoretical framework for kinetic Wulff shape predictions that accounts for the chemical environment, which we used to probe the kinetic influence of the adsorbed PVP film. Within this framework, we use umbrella-sampling molecular dynamics simulations to calculate the potential of mean force and diffusion coefficient profiles of Ag atom deposition onto Ag(100) and Ag(111) in ethylene glycol solution with surface-adsorbed PVP. We use these profiles to calculate the mean-first passage times and implement extensive Brownian dynamics simulations, which allows the kinetic effects to be quantitatively evaluated. Our results show that PVP films can regulate the flux of Ag atoms to be greater towards Ag(111) than Ag(100). PVP's preferential binding towards Ag(100) over Ag(111) gives PVP its flux-regulating capabilities through the lower free-energy barrier of Ag atoms to cross the lower-density PVP film on Ag(111) and enhanced Ag trapping by the extended PVP film on Ag(111). Under kinetic control, {100}-faceted nanocrystals will be formed when the Ag flux is greater towards Ag(111). The predicted kinetic Wulff shapes are in agreement with the analogous experimental system.

  12. Radionuclide Imaging of Musculoskeletal Infection: A Review.

    PubMed

    Palestro, Christopher J

    2016-09-01

    There are numerous imaging tests for diagnosing musculoskeletal infection. Radiographs are routinely performed, because even when not diagnostic, they provide an anatomic overview of the region of interest that could influence subsequent procedure selection and interpretation. MRI is sensitive and provides superb anatomic detail. Bone scintigraphy accurately diagnoses osteomyelitis in bones not affected by underlying conditions. (67)Ga is used primarily for spondylodiskitis. Although in vitro labeled leukocyte imaging is the radionuclide test of choice for complicating osteomyelitis such as diabetic pedal osteomyelitis and prosthetic joint infection, it is not useful for spondylodiskitis. Antigranulocyte antibodies and antibody fragments have limitations and are not widely available. (111)In-biotin is useful for spondylodiskitis. Radiolabeled synthetic fragments of the antimicrobial peptide ubiquicidin are promising infection-specific agents. (18)F-FDG is the radiopharmaceutical of choice for spondylodiskitis. Its role in diabetic pedal osteomyelitis and prosthetic joint infection is not established. Preliminary data suggest (68)Ga may be useful in musculoskeletal infection. (124)I-fialuridine initially showed promise as an infection-specific radiopharmaceutical, but subsequent investigations were disappointing. The development of PET/CT and SPECT/CT imaging systems, which combine anatomic and functional imaging, has revolutionized diagnostic imaging. These hybrid systems are redefining the diagnostic workup of patients with suspected or known infection and inflammation by improving diagnostic accuracy and influencing patient management.

  13. Radionuclide imaging of bone marrow disorders.

    PubMed

    Agool, Ali; Glaudemans, Andor W J M; Boersma, Hendrikus H; Dierckx, Rudi A J O; Vellenga, Edo; Slart, Riemer H J A

    2011-01-01

    Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as (99m)Tc-nanocolloid, (99m)Tc-sulphur colloid, (111)In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using (18)F-FDG and (18)F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.

  14. Cutting a chemical bond with demon's scissors: Mode- and bond-selective reactivity of methane on metal surfaces

    NASA Astrophysics Data System (ADS)

    Lozano, A.; Shen, X. J.; Moiraghi, R.; Dong, W.; Busnengo, H. F.

    2015-10-01

    In this paper we discuss several aspects of methane reactive sticking on Pt(111) in the light of supersonic molecular beam experiments (including state-resolved measurements) and quasi-classical trajectory calculations based on an accurate reaction specific reactive force field constructed from Density Functional Theory (DFT) data. With the aim of understanding the origin of the full bond selectivity recently achieved experimentally and to predict how selectivity depends on the collision conditions, we discuss in detail, the role of initial translational and (mode-specific) vibrational energy of CH4 and all its deuterated isotopomers, as well as surface temperature effects. Last but not least, the systematic and detailed theoretical analysis presented here serves as an illustration of the possibilities and usefulness of accurate reaction specific reactive force fields built from DFT data. This approach allows investigating dynamical aspects of the interaction of polyatomic molecules on surfaces through quasi-classical trajectory calculations accounting for the full dimensionality of the system (including both molecular and surface degrees of freedom): something that a few years ago was just a dream for the gas-surface dynamics community.

  15. Mechanical and Thermal Properties of Praseodymium Monopnictides: AN Ultrasonic Study

    NASA Astrophysics Data System (ADS)

    Bhalla, Vyoma; Kumar, Raj; Tripathy, Chinmayee; Singh, Devraj

    2013-09-01

    We have computed ultrasonic attenuation, acoustic coupling constants and ultrasonic velocities of praseodymium monopnictides PrX(X: N, P, As, Sb and Bi) along the <100>, <110>, <111> in the temperature range 100-500 K using higher order elastic constants. The higher order elastic constants are evaluated using Coulomb and Born-Mayer potential with two basic parameters viz. nearest-neighbor distance and hardness parameter in the temperature range of 0-500 K. Several other mechanical and thermal parameters like bulk modulus, shear modulus, Young's modulus, Poisson ratio, anisotropic ratio, tetragonal moduli, Breazeale's nonlinearity parameter and Debye temperature are also calculated. In the present study, the fracture/toughness (B/G) ratio is less than 1.75 which implies that PrX compounds are brittle in nature at room temperature. The chosen material fulfilled Born criterion of mechanical stability. We also found the deviation of Cauchy's relation at higher temperatures. PrN is most stable material as it has highest valued higher order elastic constants as well as the ultrasonic velocity. Further, the lattice thermal conductivity using modified approach of Slack and Berman is determined at room temperature. The ultrasonic attenuation due to phonon-phonon interaction and thermoelastic relaxation mechanisms have been computed using modified Mason's approach. The results with other well-known physical properties are useful for industrial applications.

  16. Effect of Desiccating Stress on Mouse Meibomian Gland Function

    PubMed Central

    Suhalim, Jeffrey L.; Parfitt, Geraint J.; Xie, Yilu; De Pavia, Cintia S.; Pflugfelder, Stephen C.; Shah, Tejas N.; Potma, Eric O.; Brown, Donald J.; Jester, James V.

    2013-01-01

    Purpose Mice exposed to standardized desiccating environmental stress to induce dry eye-like symptoms have been used as a model to study the underlying mechanisms of evaporative dry eye. While studies have shown marked inflammatory and immune changes, the effect of such stress on meibomian gland function remains largely unknown. We sought to evaluate the effects of desiccating stress on meibocyte proliferation and meibum quality. Methods Ten mice were treated with scopolamine and subjected to a drafty low humidity environment (30–35%). Five and ten days after treatment, eyelids were harvested and cryosections stained with Ki67 antibody to identify cycling cells. Sections were also imaged using stimulated Raman scattering (SRS) microscopy to characterize the gland compositional changes by detecting the vibrational signatures of methylene (lipid) and amide-I (protein). Results Desiccating stress caused a 3-fold increase in basal acinar cell proliferation from 18.3 ± 11.1% in untreated mice to 64.4 ± 19.9% and 66.6 ± 13.4% after 5 and 10 days exposure, respectively (P < .001). In addition, SRS analysis showed a wider variation in the protein-to-lipid ratio throughout the gland, suggesting alterations in meibocyte differentiation and lipid synthesis. Conclusions These data are consistent with a model that a desiccating environment may have a direct effect on meibomian gland function, leading to a significant increase in basal acinar cell proliferation, abnormal meibocyte differentiation, and altered lipid production. PMID:24439047

  17. A small-scale anatomical dosimetry model of the liver

    NASA Astrophysics Data System (ADS)

    Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

    2014-07-01

    Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and 125I, 90Y, 211At, 99mTc, 111In, 177Lu, 131I and 18F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons (125I) or high-LET alpha particles (211At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

  18. Controlling Molecular Growth between Fractals and Crystals on Surfaces.

    PubMed

    Zhang, Xue; Li, Na; Gu, Gao-Chen; Wang, Hao; Nieckarz, Damian; Szabelski, Paweł; He, Yang; Wang, Yu; Xie, Chao; Shen, Zi-Yong; Lü, Jing-Tao; Tang, Hao; Peng, Lian-Mao; Hou, Shi-Min; Wu, Kai; Wang, Yong-Feng

    2015-12-22

    Recent studies demonstrate that simple functional molecules, which usually form two-dimensional (2D) crystal structures when adsorbed on solid substrates, are also able to self-assemble into ordered openwork fractal aggregates. To direct and control the growth of such fractal supramolecules, it is necessary to explore the conditions under which both fractal and crystalline patterns develop and coexist. In this contribution, we study the coexistence of Sierpiński triangle (ST) fractals and 2D molecular crystals that were formed by 4,4″-dihydroxy-1,1':3',1″-terphenyl molecules on Au(111) in ultrahigh vacuum. Growth competition between the STs and 2D crystals was realized by tuning substrate and molecular surface coverage and changing the functional groups of the molecular building block. Density functional theory calculations and Monte Carlo simulations are used to characterize the process. Both experimental and theoretical results demonstrate the possibility of steering the surface self-assembly to generate fractal and nonfractal structures made up of the same molecular building block.

  19. Ab Initio Based 2D Continuum Mechanics - Sensitivity Prediction for Contact Resonance Atomic Force Microscopy Based Structure Fingerprints

    NASA Astrophysics Data System (ADS)

    Tu, Qing; Lange, Björn; Lopes, J. Marcelo J.; Zauscher, Stefan; Blum, Volker

    Contact resonance AFM is demonstrated as a powerful tool for mapping differences in the mechanical properties of 2D materials and heterostructures, permitting to resolve surface and subsurface structural differences of different domains. Measured contact resonance frequencies are related to the contact stiffness of the combined tip-sample system. Based on first principles predicted elastic properties and a continuum approach to model the mechanical impedance, we find contact stiffness ratios between different domains of few-layer graphene on 3C-SiC(111) in excellent agreement with experiment. We next demonstrate that the approach is able to quantitatively resolve differences between other 2D materials domains, e.g., for h-BN, MoS2 and MoO3 on graphene on SiC. We show that the combined effect of several materials parameters, especially the in-plane elastic properties and the layer thickness, determines the contact stiffness, therefore boosting the sensitivity even if the out-of-plane elastic properties are similar.

  20. The Cost of Relapsing-Remitting Multiple Sclerosis Patients Who Develop Neutralizing Antibodies during Interferon Beta Therapy

    PubMed Central

    Iannazzo, Sergio; Santoni, Laura; Iaffaldano, Antonio; Di Lecce, Valentina; Manni, Alessia; Lavolpe, Vito; Tortorella, Carla; D'Onghia, Mariangela; Direnzo, Vita; Puma, Elisa; Trojano, Maria

    2016-01-01

    Background Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with interferon beta (IFN beta) can develop neutralizing antibodies (NAbs) that reduce treatment efficacy. Several clinical studies explored the association of NAb+ status with increased disease activity. Objective The aim of this study was to estimate the cost of RRMS patients who develop NAbs while treated with IFN beta by the Italian National Healthcare Service (NHS) and the Italian Society perspectives. Methods The clinical data derived from a published observational study on 567 RRMS Italian patients treated with IFN beta. The management cost data derived from the published literature. Cost data were inflated to Euro 2014. Results The annual direct cost to treat a patient was estimated in €15,428 in the NAb+ cohort and €14,317 in the NAb- cohort. The annual societal cost was estimated in €33,890 and €30,790 in NAb+ and NAb- patients, respectively. The cost increase related to the NAb+ status was €3,100 in the Italian societal perspective and €1,111 in the Italian NHS perspective. Conclusion The results of this economic evaluation suggest the presence of an association between NAb+ status and increased costs for the management of RRMS in Italy. Further pharmacoeconomic research will be needed to confirm this first result. PMID:27390865

  1. Fullerene-derivative PC61BM forms three types of phase-pure monolayer on the surface of Au(111)

    NASA Astrophysics Data System (ADS)

    Li, Wen-Jie; Du, Ying-Ying; Zhang, Han-Jie; Chen, Guang-Hua; Sheng, Chun-Qi; Wu, Rui; Wang, Jia-Ou; Qian, Hai-Jie; Ibrahim, Kurash; He, Pi-Mo; Li, Hong-Nian

    2016-12-01

    We have studied the packing structures of C60-derivative PC61BM on the surface of Au(111) in ultrahigh vacuum using scanning tunneling microscopy. The Au(111) has a triangle-like reconstructed surface, which results in some packing structures different from those reported for low coverages. PC61BM can form three types of phase-pure monolayer, namely, the compact straight molecular double-row monolayer, the hexagonal-packing monolayer and the glassy monolayer. The different types of monolayer form for different molecular densities and different annealing temperatures. In addition to the already known inter-molecular interactions (Van de Waals interaction and hydrogen bond), the steric effect of the phenyl-butyric-acid-methyl-ester side tail plays conspicuous role in the molecular self-assembly at high coverages. The steric effect makes it difficult to prepare a hexagonal-packing monolayer at room temperature and decides the instability of the hexagonal-packing monolayer prepared by thermal annealing.

  2. Micellar cathodes from self-assembled nitroxide-containing block copolymers in battery electrolytes.

    PubMed

    Hauffman, Guillaume; Maguin, Quentin; Bourgeois, Jean-Pierre; Vlad, Alexandru; Gohy, Jean-François

    2014-01-01

    This contribution describes the synthesis of block copolymers containing electrochemically active blocks, their micellization, and finally their use as micellar cathodes in a lithium battery. The self-assembly of the synthesized poly(styrene)-block-poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl methacrylate) (PS-b-PTMA) diblock copolymers is realized in a typical battery electrolyte made of 1 m lithium trifluoromethanesulfonate dissolved in a mixture of ethylene carbonate/diethyl carbonate/dimethyl carbonate(1:1:1, in volume). Dynamic light scattering and atomic force micro-scopy indicate the formation of well-defined spherical micelles with a PS core and a PTMA corona. The electrochemical properties of those micelles are further investigated. Cyclic voltammograms show a reversible redox reaction at 3.6 V (vs Li(+) /Li). The charge/discharge profiles indicate a flat and reversible plateau around 3.6 V (vs Li(+) /Li). Finally, the cycling performances of the micellar cathodes are demonstrated. Such self-assembled block copolymers open new opportunities for nanostructured organic radical batteries.

  3. Opening gates to oxygen reduction reactions on Cu(111) surface

    SciTech Connect

    Sumer, Aslihan; Chaudhuri, Santanu

    2015-03-28

    Electrocatalytic reduction of oxygen is composed of multiple steps, including the diffusion-adsorption-dissociation of molecular oxygen. This study explores the role of electrical double layer in aqueous medium in quantifying the rate of these coupled electrochemical processes at the electrode interface during oxygen reduction. The electronic, energetic, and configurational aspects of molecular oxygen diffusion and adsorption onto Cu(111) in water are identified through density functional theory based computations. The liquid phase on Cu(111) is modeled with hexagonal-ordered water bilayers, at two slightly different structures, with O–H bonds either facing the vacuum or the metal surface. The results indicate that the energetically preferred structure of water bilayers and adsorption configuration of O{sub 2} are different in cathodic and anodic potentials. The diffusion of O{sub 2} is found to be heavily hindered at the water/metal interface because of the ordering of water molecules in bilayers as compared to the bulk liquid. The unique correlations of diffusion and adsorption kinetics with water structure identified in this work can provide clues for improving oxygen reduction efficiency.

  4. Initial generation and separation of {sup 99}Mo at Sandia National Laboratories

    SciTech Connect

    Talley, D.G.; Bourcier, S.C.; McDonald, M.J.; Longley, S.W.; Parma, E.J.

    1997-04-11

    Medical isotopes play an important role in the medical industry in both the United States and the world. Isotopes such as {sup 99}Tc, {sup 201}Tl, {sup 111}In, and {sup 123}I are utilized in diagnostic imaging studies, while others such as {sup 131}I and {sup 89}Sr are used as therapeutic agents. The particular medical isotope {sup 99m}Tc is used in 80% of all nuclear medical procedures in the United States. This isotope is produced from the decay of {sup 99}Mo, which has a 66 hour half-life. The importance of {sup 99m}Tc and the fact of its 6 hour half-life indicate the necessity to maintain a constant supply of {sup 99}Mo. The most prominent method for the production of significant quantities of {sup 99}Mo is by fission in highly-enriched uranium loaded targets. This paper describes the work performed at SNL for the production of {sup 99}Mo.

  5. Effects of Nitrogen Addition on Litter Decomposition and CO2 Release: Considering Changes in Litter Quantity

    PubMed Central

    Li, Hui-Chao; Hu, Ya-Lin; Mao, Rong; Zhao, Qiong; Zeng, De-Hui

    2015-01-01