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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. Bulky Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan

    PubMed Central

    Tamura, Shinobu; Ikeda, Tokuji; Kurihara, Toshio; Kakuno, Yoshiteru; Nasu, Hideki; Nakano, Yoshio; Oshima, Koichi; Fujimoto, Tokuzo

    2013-01-01

    An 84-year-old woman was admitted to our hospital with nonproductive cough and dyspnea on exertion. Computed tomography (CT) scan revealed extensive consolidation in the right lung. She was diagnosed with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma using CT-guided lung biopsy. Her pulmonary images and respiratory symptoms did not improve two months after receiving 4 cycles of rituximab weekly; therefore, yttrium-90 ibritumomab tiuxetan was chosen as salvage therapy. The abnormal shadow on her pulmonary images was significantly reduced two months later, and she had no symptoms without nonhematological toxicities. She has had no progression for 18 months. Furthermore, radiation pneumonitis has not also been observed. We herein reported bulky pulmonary MALT lymphoma treated with yttrium-90 ibritumomab tiuxetan. PMID:24371530

  3. 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

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

    PubMed

    Rizzieri, David

    2016-09-01

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

  5. 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. PMID:25072780

  6. 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.

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

    PubMed Central

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

    2015-01-01

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

  8. 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

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

    PubMed

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

    2014-01-01

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

  10. 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 ...

  11. Salvage therapy for primary central nervous system lymphoma with (90)Y-Ibritumomab and Temozolomide.

    PubMed

    Pitini, Vincenzo; Baldari, Sergio; Altavilla, Giuseppe; Arrigo, Carmela; Naro, Claudia; Perniciaro, Francesca

    2007-07-01

    Aggressive initial treatment of Primary Central Nervous System Lymphoma (PCNSL) has achieved prolonged survival and occasional cures. However, some patients do not respond to initial therapy and others relapse after an initial remission. The optimal salvage regimen is not known and many different strategies have been proposed. In this report we describe the efficacy of a combination of (90)Y-Ibritumomab Tiuxetan (Zevalin) and Temozolamide as a maintenance therapy for recurrent PCNS Lymphoma in two patients that are both alive and in complete remission after 9 and 10 months respectively. This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL.

  12. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313

    PubMed Central

    Miller, Thomas P.; Unger, Joseph M.; Spier, Catherine M.; Puvvada, Soham; Stea, B. Dino; Press, Oliver W.; Constine, Louis S.; Barton, Kevin P.; Friedberg, Jonathan W.; LeBlanc, Michael; Fisher, Richard I.

    2015-01-01

    In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT. Forty-six patients were registered and eligible, with median follow-up of 7.3 years. The progression-free survival estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events occurring more than once included neutropenia (8), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. In conclusion, patients with high-risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. The clinical trial was registered at www.clinicaltrials.gov as #NCT00070018. PMID:25395425

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

    ClinicalTrials.gov

    2016-06-15

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

  14. 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

  15. 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

  16. 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

  17. 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

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

    ClinicalTrials.gov

    2016-07-08

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

  19. 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

  20. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

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

  1. Gateways to clinical trials.

    PubMed

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

    2003-10-01

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

  2. Immunoscintigraphy with 111In antimyosin Fab.

    PubMed

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

    1990-11-01

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

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

    SciTech Connect

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

    1989-01-01

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

  4. 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.

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

    PubMed

    Dziel, Tomasz; Listkowska, Anna; Tymiński, Zbigniew

    2016-03-01

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

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

    PubMed

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

    1986-07-01

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

  7. 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

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

    PubMed

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

    2014-02-28

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

  9. /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.

  10. Biodistribution of 111In-labelled IgG and IgM in experimental infection.

    PubMed

    Oyen, W J; Boerman, O C; Subramanian, R; Koenders, E B; Claessens, R A; van der Meer, J W; Corstens, F H

    1996-07-01

    Both the protein used and the conjugation method are factors which may be relevant for targeting infection with 111In-labelled proteins. In this study, human immunoglobulin G (IgG), conjugated to either DTPA or LiLo, and LiLo conjugated human immunoglobulin M (IgM) were evaluated. In rats with Staphylococcus aureus calf muscle infection, biodistribution was determined 6, 24 and 48 h after the injection of 111In-DTPA-IgG, 111InLiLo-IgG or 111In-LiLo-IgM. Absolute abscess uptake of 111In-LiLo-IgG was significantly higher than that of 111In-DTPA-IgG (P < 0.05). Since blood clearance of 111In-LiLo-IgG was initially significantly slower (P < 0.01), the higher abscess uptake did not result in higher abscess-to-background ratios. 111In-LiLo-IgG accumulated to a greater extent in the liver (P < 0.001). 111In-DTPA-IgG showed higher uptake in the kidneys and bone marrow (P < 0.001 and P < 0.01, respectively). Although decreasing over time, 111In-LiLo-IgM showed reasonable abscess uptake and rapid blood clearance, resulting in higher abscess-to-background ratios compared with 111In-LiLo-IgG (P < 0.01). However, liver and spleen uptake were three- to four-fold higher than that of 111In-LiLo-IgG (P < 0.001). Compared with DTPA-conjugation, chelation with LiLo has a minor influence on abscess targeting of 111In-labelled IgG. However, differences in blood clearance and organ uptake do occur. 111In-LiLo-IgM shows high relative accumulation in abscesses as well as high liver and spleen uptake. 111In-LiLo-IgM appears promising for imaging infection outside the trunk region.

  11. Uptake of /sup 111/In-labeled leukocytes by tumor

    SciTech Connect

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

    1986-03-01

    The 111In-labeled leukocyte scan is a sensitive and specific technique for the detection and localization of abscesses. However, in reviewing an unselected series of 249 scans, six (2.3%) were false-positive cases in which leukocyte uptake by tumor mimicked an abscess. This represented 12% (6/51) with known tumor at the time of imaging. Five of the cases were primary or metastatic tumors to the soft tissues; the sixth was a skeletal metastasis. The intensity of tumor activity has been characterized as mild in the few cases of leukocyte uptake reported in the literature, suggesting that the degree of uptake is helpful in distinguishing tumor from abscess. In this study, however, variable degrees of tumor-associated activity were seen ranging from mild to very intense. These findings indicate that tumor accumulates labeled leukocytes more frequently than has been previously appreciated, that primary and metastatic neoplasms involving both the soft tissues and skeleton are involved, and that the intensity of uptake is not a reliable criterion to distinguish tumor from abscess.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Radioactivity measurements of 177Lu, 111In and 123I by different absolute methods.

    PubMed

    Rezende, E A; Correia, A R; Iwahara, A; da Silva, C J; Tauhata, L; Poledna, R; da Silva, R L; de Oliveira, E M; de Oliveira, A E

    2012-09-01

    The activities of (177)Lu, (111)In and (123)I solutions have been absolutely determined using three different measurement methods. (177)Lu solution was standardized using the 4πβ(PC)-γ(NaI) coincidence and 4πβ(LS)-γ(NaI) live-timed anticoincidence methods. For the (111)In and (123)I solutions, besides these two mentioned methods, the coincidence sum-peak method was also applied. The measured activities results using these different methods are consistent within the evaluated experimental uncertainties demonstrating the equivalence of these methods. As an additional contribution to nuclear data, the half-lives have been determined using a well type IG12 ionization chamber.

  20. Radioactivity measurements of 177Lu, 111In and 123I by different absolute methods.

    PubMed

    Rezende, E A; Correia, A R; Iwahara, A; da Silva, C J; Tauhata, L; Poledna, R; da Silva, R L; de Oliveira, E M; de Oliveira, A E

    2012-09-01

    The activities of (177)Lu, (111)In and (123)I solutions have been absolutely determined using three different measurement methods. (177)Lu solution was standardized using the 4πβ(PC)-γ(NaI) coincidence and 4πβ(LS)-γ(NaI) live-timed anticoincidence methods. For the (111)In and (123)I solutions, besides these two mentioned methods, the coincidence sum-peak method was also applied. The measured activities results using these different methods are consistent within the evaluated experimental uncertainties demonstrating the equivalence of these methods. As an additional contribution to nuclear data, the half-lives have been determined using a well type IG12 ionization chamber. PMID:22401938

  1. 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.

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

    SciTech Connect

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

    1990-02-01

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

  3. Diagnosis of abdominal abscesses with computed tomography, ultrasound, and /sup 111/In leukocyte scans

    SciTech Connect

    Knochel, J.Q.; Koehler, P.R.; Lee, T.G.; Welch, D.M.

    1980-11-01

    Computed tomography (CT), ultrasound, and /sup 111/In-labeled leukocyte scans are all used in the evaluation of abdominal abscesses. In this study, 170 patients in whom one, two, or all three of these modalities were used were retrospectively reviewed. Diagnostic accuracy of 96% for CT, 90% for ultrasound, and 92% for /sup 111/In leukocyte scans was achieved. It was often necessary to use more than one modality to arrive at a correct diagnosis. The advantages and disadvantages as well as the causes for false positive or false negative interpretations of each of these modalities are reviewed. Analysis of the different examinations resulted in a suggested sequence by which patients can be examined, based upon their clinical condition. Patients who are not critically ill and/or who have no localizing signs should be studied first with /sup 111/In-labeled leukocyte scans. If, however, localizing signs are present or the patient's condition necessitates prompt intervention, CT or ultrasound should be the first study performed.

  4. 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.

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

    PubMed

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

    2015-11-01

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

  6. /sup 111/In-platelet survival kinetics: Tropolone vs oxine method

    SciTech Connect

    Vallabhajosula, S.; Machac, J.; Lipszyc, H.; Badimon, L.; Goldsmith, S.J.; Fuster, V.

    1985-05-01

    /sup 111/In-tropolone (In-tr) is being evaluated because of its greater affinity for platelets in plasma than /sup 111/In-oxine (In-ox). Platelets separated from a 50 ml blood sample were labeled with In-tr in 2 ml autologous plasma and In-ox in 4 ml ACD-saline. 10 blood samples starting at 1 hr were obtained over a 8 day period. Platelet survival was calculated based on linear, exponential and multi hit analysis. The life-span of platelets measured by tropolone and oxine methods were compared in the same 8 normal human subjects and were performed 2 months apart. With In-tr, the platelet recovery is higher at 1 hr and throughout the 8-days and the gamma camera images showed less uptake in liver and spleen than In-ox. In addition, linear model is the best fit (63%) with a life-span equal or slightly longer than In-ox. Linear model is the best fit (100%) with In-ox and the multiple hit analysis also showed significantly higher number of hits (34) compared to In-tr (15). There is no correlation between in vivo recovery of /sup 111/In-platelets (tropolone or oxine) and the platelet life span. These results show that even though the platelet life span is not significantly altered by labeling method, they are better preserved in circulation when labeled with In-tr.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

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

    SciTech Connect

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

    2008-06-01

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

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

    SciTech Connect

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

    1982-04-01

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

  11. 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.

  12. PAC investigations of radiation damage annealing in 111In implanted ZnO

    NASA Astrophysics Data System (ADS)

    Dogra, R.; Byrne, A. P.; Ridgway, M. C.

    2009-08-01

    The structural and electronic environment about implanted radioactive 111In(→ 111Cd) probe atoms as a function of annealing temperature in a single crystal of ZnO(0 0 0 1) has been monitored on an atomic scale using perturbed angular correlation technique, a nuclear hyperfine method. This technique is based upon the hyperfine interaction of the nuclear electric quadrupole moment or magnetic moment of the probes, respectively, with the electric field gradient or magnetic hyperfine field arising from the extra-nuclear electronic charges and spin distributions. The probe atoms 111In were recoil-implanted at room temperature following heavy-ion nuclear reactions. The electric quadrupole interaction was measured at room temperature for as-implanted and annealed samples. The thermal annealing in ambient nitrogen up to 1000 °C showed a progressive reduction of disorder around the probe atom as evidenced via continual decrease in width of the distribution of quadrupole interaction frequencies. Present measurements suggested that annealing at 800 °C for 30 min in flowing nitrogen is enough to produce an optimum recovery of crystallinity. After annealing of radiation damage at 1000 °C we observed an axially symmetric electric field gradient which is characterized by the unique quadrupole interaction frequency of 30.6(3) MHz and a frequency distribution of width nearly zero. The observed electric field gradient was attributed to substitutional incorporation of probe atoms at cation-sites of ZnO. In contrast to annealing in ambient nitrogen at 1000 °C, air annealing of 111In implanted ZnO samples revealed change in local stoichiometry about probe atoms which is attributed to the internal oxidation of the indium probes. The measured electric field gradient and asymmetry parameter at cation-sites of ZnO have been compared with theoretical calculations using a simple point charge model.

  13. Whole body and tomographic scan with 111In-pentetreotide: preliminary data.

    PubMed

    Gregianin, M; Macrì, C; Bui, F; Varotto, L; Zucchetta, P

    1995-12-01

    Since December 1993, in the 1st Nuclear Medicine Service of the University of Padua, eleven somatostatin-receptor scintigraphic studies with 111In-labelled pentetreotide have been performed. The patients (6 men and 5 women, age 28-68, mean 45 years) were affected by a variety of tumors which supposedly express somatostatin receptors: 2 meningotheliomatous meningiomas post-surgery; 2 glucagonomas with liver metastases observed on CT; 2 patients with suspicion of insulinoma; 2 carcinoids, one after surgery; 1 ectopic-ACTH Cushing's syndrome; 1 intracranial germinoma, post-surgery, in whom the study was requested to evaluate a doubtful finding of pulmonary metastatic lesion on CT; and 1 acromegaly showing, on MRI, and empty sella turcica occupied by and extraflexion of the lower portion of the chiasmatic cisterna without signs of adenoma and the sphenoidal sinus occupied by tissue wit inflammmatory characteristics. Somatostatin-receptor whole body scintigraphy was performed 4 and 24 hours after intravenous injection of 110 MBq 111In-pentetreotide (Octreoscan 111); spot images were acquired when judged necessary. In one case of glucagonoma, a tomographic scan (SPECT) was also performed to better evaluate the spatial relationship between the primitive pancreatic tumor and surrounding tissues. Focal accumulation of 111In-pentetreotide was scintigraphically detected in 5 of the 11 cases. Intense uptake of the radiopharmaceutical was observed in the meningiomas, in the glucagonomas with liver metastases, and in the case of acromegaly, corresponding to a GH-secreting adenoma. The negative scans seem to be true negative scans with the possible exception of one patient with a still unconfirmed suspicion of insulinoma, still not confirmed.

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

    PubMed

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

    1990-02-01

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

  15. Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice

    PubMed Central

    Ho, Chung-Li; Liu, I-Hsiang; Wu, Yu-Hsien; Chen, Liang-Cheng; Chen, Chun-Lin; Lee, Wan-Chi; Chuang, Cheng-Hui; Lee, Te-Wei; Lin, Wuu-Jyh; Shen, Lie-Hang; Chang, Chih-Hsien

    2011-01-01

    Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The Cmax and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq−1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy. PMID:21660132

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

    SciTech Connect

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

    1983-02-01

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

  17. 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

  18. 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.

  19. 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.

  20. Comparison of quantification methods of 111In-labelled platelet deposition in peripheral bypass grafts.

    PubMed

    Mortelmans, L; Verbruggen, A; De Bakker, C; Vandecruys, A; Joosten, J; Nevelsteen, A; Noyez, L; Verstraete, M; Vermylen, J; De Roo, M

    1987-04-01

    The action of antithrombotic drugs can be evaluated by measuring the deposition of 111In-labelled platelets on peripheral bypass grafts several days after injection. This evaluation can be performed qualitatively (visual interpretation on the daily images) or quantitatively. Four different methods which calculate the ratio of platelet uptake with a reference region are compared: two methods use a gamma camera and two a detector. A blood sample or the region under the sternal angle are used as reference. The daily ratio of the counts, recorded by a gamma camera in a region of interest covering the graft, and the blood radioactivity interpolated from a platelet survival curve appears to be the most reliable method. The information of all the ratios can be combined in a single thrombogenicity index which reflects the daily rise of a linear or exponential regression versus time. PMID:3588323

  1. 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.

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

    SciTech Connect

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

    1984-04-01

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

  3. 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.

  4. 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.

  5. Detection of thrombophlebitis with 111In-labeled anti-fibrin antibody: Preliminary results

    SciTech Connect

    Alavi, A.; Gupta, N.; Palevsky, H.I.; Kelley, M.A.; Jatlow, A.D.; Byar, A.A.; Berger, H.J. )

    1990-02-01

    Deep venous thrombosis remains a major medical problem, affecting a large segment of the population and resulting in significant mortality and morbidity. Current techniques available for detecting deep venous thrombosis present limitations that may mitigate their potential benefit to the patient. Invasive techniques, such as ascending contrast venography, carry risks to the patient with regard to complications such as an allergic reaction to an iodine dye, adverse effects to renal functions, and clot formation in a normal vein. Noninvasive techniques, such as Doppler ultrasound and impedance plethysmography, evaluate only a limited segment of the venous bed. The need remains for a diagnostic technique that is safe, accurate, and widely accessible. A readily available noninvasive scintigraphic technique utilizing radiolabeled monoclonal anti-fibrin antibody may overcome some of these shortcomings. This imaging examination is quite effective in detecting clots in the lower extremities. Compared to contrast venography, {sup 111}In-labeled anti-fibrin antibody imaging appears to be as sensitive in identifying acute venous thrombosis. In addition, the preliminary data indicate that anticoagulation with heparin may interfere with adequate visualization of the clots with this technique.

  6. 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.

  7. 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. PMID:27472826

  8. Gateways to clinical trials.

    PubMed

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

    2005-06-01

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

  9. 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.

  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. 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.

  12. A comparison of 111In-HIG scintigraphy and chest radiology in the identification of pulmonary infection in patients with HIV infection.

    PubMed

    Buscombe, J R; Oyen, W J; Corstens, F H; Ell, P J; Miller, R F

    1995-05-01

    Prospectively, we compared the results of chest radiology and functional imaging, using 111In-labelled polyclonal human IgG (111In-HIG), in the identification of pulmonary infection in patients infected by the human immunodeficiency virus (HIV). Sixty-three studies were performed on 57 HIV-infected patients presenting with suspected chest infection or fever of unknown cause, in each of whom a planar chest radiograph was obtained within 24 h of the 111In-HIG study. The results of the two imaging modalities were compared with the final microbiological or cytological diagnosis. Forty patients were found to have pulmonary infection, 25 of whom were correctly identified with chest radiology (sensitivity 62%) and 39 with 111In-HIG (sensitivity 97%). In those patients without infection, chest radiology was abnormal in 13 cases (specificity 43%), while there was only one false-positive 111In-HIG study (specificity 95%). 111In-HIG correctly identified the presence or absence of active lung infection in 61 of 63 cases (accuracy 93%). This was significantly better (chi 2 = 8.25, upsilon = 1, P < 0.01) than chest radiology, which correctly identified the presence or absence of infection in 35 of 63 cases (accuracy 55%). In HIV antibody-positive patients, functional imaging with 111In-HIG is more accurate than chest X-ray in the identification of pulmonary infection.

  13. (111)In-trastuzumab scintigraphy in HER2-positive metastatic breast cancer patients remains feasible during trastuzumab treatment.

    PubMed

    Gaykema, Sietske B M; de Jong, Johan R; Perik, Patrick J; Brouwers, Adrienne H; Schröder, Carolien P; Oude Munnink, Thijs H; Bongaerts, Alphons H H; de Vries, Elisabeth G E; Lub-de Hooge, Marjolijn N

    2014-01-01

    Human epidermal growth factor receptor (HER)2 imaging with radiolabeled trastuzumab might support HER2-targeted therapy. It is, however, frequently questioned whether HER2 imaging is also possible during trastuzumab treatment as the receptor might be saturated. We studied the effect of trastuzumab treatment on 111In-trastuzumab uptake. Patients received trastuzumab weekly and paclitaxel once every 3 weeks. 111In-trastuzumab was injected on day 1 of cycle 1 and day 15 of cycle 4. Whole-body planar scintigraphy was acquired at different time points postinjection. Tumor uptake and organ distribution between the first and repeated scan series were calculated via residence times. Twenty-five tumor lesions in 12 patients were visualized on both scintigraphy series. Tumor uptake decreased (19.6%; p  =  .03). The residence times of normal organs remained similar except for the cardiac blood pool (+ 16.3%; p  =  .014). Trastuzumab treatment decreases tumor 111In-trastuzumab uptake around 20%. HER2 imaging is feasible during trastuzumab treatment.

  14. Melanoma Imaging using 111In, 86Y and 68Ga labeled CHX-A”-Re(Arg11)CCMSH

    PubMed Central

    Wei, Lihui; Zhang, Xiuli; Gallazzi, Fabio; Miao, Yubin; Jin, Xiaofang; Brechbiel, Martin W.; Xu, Heng; Clifford, Thomas; Welch, Michael J.; Lewis, Jason S.; Quinn, Thomas P.

    2009-01-01

    Introduction A novel alpha-melanocyte stimulating hormone peptide analog CHX-A”-Re(Arg11)CCMSH, that targeted the melanocortin-1 receptor (MC1-R) over-expressed on melanoma cells, was investigated for its biodistribution and tumor imaging properties. Methods The metal bifunctional chelator CHX-A” was conjugated to the melanoma targeting peptide (Arg11)CCMSH and cyclized by Re incorporation to yield CHX-A”-Re(Arg11)CCMSH. CHX-A”-Re(Arg11)CCMSH was labeled with 111In, 86Y and 68Ga and the radiolabeled peptides were examined in B16/F1 melanoma bearing mice for their pharmacokinetic as well as their tumor targeting properties using small animal SPECT and PET. Results The radiolabeling efficiencies of the 111In, 86Y and 68Ga labeled CHX-A”-Re(Arg11)CCMSH peptides were > 95%, resulting in specific activities of 4.44 GBq/μg, 3.7 GBq/μg and 1.85 GBq/μg, respectively. Tumor uptake of the 111In, 86Y and 68Ga labeled peptides was rapid with 4.17±0.94 % ID/g, 4.68±1.02 % ID/g and 2.68±0.69 % ID/g present in the tumors 2 h post injection, respectively. Disappearance of radioactivity from the normal organs and tissues was rapid with the exception of the kidneys. Melanoma tumors were imaged with all three radiolabeled peptides 2 h post injection. MC1-R specific uptake was confirmed by competitive receptor blocking studies. Conclusions Melanoma tumor uptake and imaging was exhibited by the 111In, 86Y and 68Ga labeled -Re(Arg11)CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A”-Re(Arg11)CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after 111In, 86Y and 68Ga labeling. PMID:19423001

  15. 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

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

    PubMed

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

    2008-04-01

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

  17. 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.

  18. Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts

    SciTech Connect

    Isobe, M.; Haber, E.; Khaw, B.A. )

    1991-09-01

    Mice (n = 58) with abdominal heterotopic heart transplants were studied to examine the effectiveness of 111In-labeled antimyosin scintigraphy in the detection of rejection and to determine the consequence of cyclosporine therapy on the results. Allografts from B10D2 donors were transplanted into B6AF1 recipients. Of the 49 allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine isografted mice served as controls. Scintigraphy was performed by injecting 100 muCi 111In antimyosin monoclonal antibody 2-15 days after transplantation. An increase in the ratio of percent dose of antimyosin injected per gram (% dose/g) of the grafted heart (G) to that of the autologous heart (A) (G/A) as well as the increasing percent dose per gram of antimyosin in the grafts reflected the severity of histopathological rejection regardless of the presence or absence of cyclosporine. Scintigraphic images demonstrated unequivocally intense accumulation of 111In in rejected allografts as confirmed by histologically demonstrable myocyte necrosis. The G/A ratio in allografted mice with mildly deteriorated mechanical activity (4.2 {plus minus} 1.0, mean {plus minus} SD) was greater than that in mice with normal contractility (1.8 {plus minus} 0.7) (p less than 0.001), and the necrosis correlated with this modest decline in mechanical function could be scintigraphically identified. Of mice with normally contracting allografts, the G/A ratio was greater in animals with demonstrated myocyte necrosis (2.6 {plus minus} 0.5) than in those without necrosis (1.5 {plus minus} 0.5) (p less than 0.001). In contrast, isografted mice or a subset of allografted mice treated with cyclosporine and not showing evidence of rejection did not manifest any significant change in G/A ratio, nor did they have scintigrams positive for rejection as late as 15 days after transplantation.

  19. Interaction of ethanol with 111In-labelled membranes: evaluation by the perturbed angular correlation-sum peak ratio method.

    PubMed

    Jay, M; Woodward, M A

    1985-08-01

    The interaction of ethanol with erythrocyte ghosts and vesicles composed of brain lipid extracts labelled with indium-111 was studied using the sum peak ratio method of perturbed angular correlation measurements. Membranes from animals that were fed diets containing ethanol for 10 days demonstrated resistance to the decrease in sum peak ratio values observed in control animals. Thus, repeated administration of ethanol induces changes in the properties of biological membranes, possibly by altering phospholipid composition, which is reflected in the anisotropy of membrane-associated 111In-labelled nuclei as measured by sum peak ratios.

  20. Growth of Pb nanowires on the Si(111)-In (4x1) a combined STM and SPALEED study

    NASA Astrophysics Data System (ADS)

    Hupalo, Myron; Yakes, Michael; Tringides, Michael

    2006-03-01

    Due to the combined effect of QSE and the anisotropic strain potential of the substrate, Pb deposited on Si(111)-In (4x1) at 180K grows in nanowires of uniform 4-layer height and controllable uniform width of 5w0 { (}where w0=1.33nm is the width of the reconstruction unit cell along [1&_slash;1&_slash;2] direction). SPA-LEED studies confirm this selected 4-layer height (from Intensity vs Kz variation) which is unusually stable because it is unchanged even after annealing to room temperature. The same selected 4-layer height is observed on a different interface Si(111)-In √ 31x√ 31 which independently confirms the unusual 4-layer stability. Differences in the observed corrugation on the tops of the nanowires due to the Moir'{e} pattern at the metal/semiconductor interface confirm the strain anisotropy on the reconstructed substrate. Further Pb deposition on top of the nanowires results in the completion of the Pb layer with unusually atomically flat film interfaces over mesoscopic distances.

  1. 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.

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

    PubMed

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

    2015-04-01

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

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

    SciTech Connect

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

    1983-11-01

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

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

    PubMed

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

    2005-03-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-10-23

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

  7. /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.

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

    SciTech Connect

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

    1982-07-01

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

  9. Comparison of yttrium and indium complexes of DOTA-BA and DOTA-MBA: models for (90)Y- and (111)In-labeled DOTA-biomolecule conjugates.

    PubMed

    Liu, Shuang; Pietryka, John; Ellars, Charles E; Edwards, D Scott

    2002-01-01

    Yttrium and indium complexes of 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetylbenzylamine (DOTA-BA) and 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-R-(+)-alpha-methylbenzylamine (DOTA-MBA) were prepared in order to study solution structures of (90)Y- and (111)In-labeled DOTA-biomolecule conjugates. (90)Y and (111)In complexes M(L) (M = (90)Y and (111)In; L = DOTA-BA and DOTA-MBA) were prepared from the reaction of MCl(3) with DOTA-BA and DOTA-MBA, respectively, in ammonium acetate buffer. A reverse phase HPLC method revealed that both (90)Y and (111)In complexes show only one radiometric peak in their radio-HPLC chromatograms. It was also found that (111)In(DOTA-BA) and (111)In(DOTA-MBA) are more hydrophilic than their corresponding (90)Y analogues, suggesting different coordination spheres in (111)In and (90)Y complexes of the same DOTA conjugate. Complexes M(L) (M = Y and In; L = DOTA-BA and DOTA-MBA) were prepared and characterized by HPLC, LC-MS, and NMR ((1)H and (13)C) methods. The HPLC concordance experiments for (90)Y(DOTA-MBA)/Y(DOTA-MBA) and (111)In(DOTA-MBA)/In(DOTA-MBA) show that the same complex is prepared at both tracer and macroscopic levels. The NMR data ((1)H and (13)C) clearly demonstrates that Y(DOTA-BA) and Y(DOTA-MBA) exist in solution as one predominant isomer. VT NMR data ((1)H and (13)C) show that In(DOTA-BA) and In(DOTA-MBA) are fluxional at room temperature while Y(DOTA-BA) and Y(DOTA-MBA) become fluxional only at elevated temperatures. The fluxionality of these complexes is due to rapid rotation of acetate/acetamide chelating arms and inversion of ethylenic groups of the macrocyclic ring.

  10. Immunoscintigraphy of prostatic cancer: preliminary results with sup 111 In-labeled monoclonal antibody 7E11-C5. 3 (CYT-356)

    SciTech Connect

    Wynant, G.E.; Murphy, G.P.; Horoszewicz, J.S.; Neal, C.E.; Collier, B.D.; Mitchell, E.; Purnell, G.; Tyson, I.; Heal, A.; Abdel-Nabi, H. )

    1991-01-01

    A phase 1 study was conducted with the investigational immunoscintigraphic agent, {sup 111}In-CYT-356, a radiolabeled, site-specific immunoconjugate of monoclonal antibody 7E11-C5.3, in 40 patients with prostatic carcinoma and known distant metastases. Each patient received a single intravenous infusion of CYT-356 (dose range, 0.1-5 mg) radiolabeled with approximately 5 mCi of {sup 111}In. None of the patients experienced adverse reactions. One patient who received a 5-mg dose developed antibodies to the CYT-356 immunoconjugate. {sup 111}In-CYT-356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow-up imaging tests, in one patient. Higher CYT-356 doses may clear the blood pool more slowly. These results suggest that {sup 111}In-CYT-356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.

  11. ( 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.

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

    PubMed Central

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

    2000-01-01

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

  13. 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.

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

    SciTech Connect

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

    1996-02-15

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

  15. 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

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

    PubMed

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

    1995-12-01

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

  17. The non tumour uptake of (111)In-octreotide creates new clinical indications in benign diseases, but also in oncology.

    PubMed

    Cascini, G L; Cuccurullo, V; Mansi, L

    2010-02-01

    The use of somatostatin (SS) analogues in humans takes advantage by the availability of many related chemical forms that can be used for receptor therapy and, after radiolabelling, for diagnostic imaging and radionuclide therapy. The first proposed radiocompound, yet clinically widely diffuse, has been (111)In-octreotide (OCT), followed by positron emission tomography (PET) and beta emitter tracers. The main field of clinical applications is in neuroendocrine tumours (NET), starting by the demonstration of SS receptors (SSR) on the majority of NET, particularly on gastroenteropancreatic (GEP) tumours. Uptake of SS analogues can also be due to a SSR expression on non malignant cells when activated, as lymphocytes, macrophages, fibroblasts , vascular cells. Because of this uptake clinical indications can be found also in active benign diseases, as Grave's ophthalmopathy, rheumatoid arthritis, histiocitosis, sarcoidosis, idiopatic pulmonary fibrosis. Moreover, these cells can also determine the OCT in vivo uptake in tumours non expressing in vitro SSR, as non-snall cell lung cancer (NSCLC). Because of a different kinetic respect to SCLC a differential histotype diagnosis could be obtained. Starting from this premise OCT can also allows radioguided surgery in tumours non expressing SSR. Finally a relevant clinical role can be defined in the a priori recruitment and as marker of therapeutic efficacy in all the therapeutic strategies utilizing SSR, both in malignant and benign diseases.

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

    SciTech Connect

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

    1983-02-01

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

  19. 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.

  20. 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.

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

    PubMed

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

    1995-07-01

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

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

    SciTech Connect

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

    2006-11-15

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

  3. Improved detection of upper abdominal abscesses by combination of /sup 99m/Tc sulfur colloid and /sup 111/In leukocyte scanning

    SciTech Connect

    Datz, F.L.; Luers, P.; Baker, W.J.; Christian, P.E.

    1985-02-01

    Indium-111-labeled leukocyte scanning is an excellent technique for detecting abdominal abscesses. However, since labeled leukocytes are normally taken up by the liver and spleen, diagnosing upper abdominal abscesses can be difficult. A prospective study was undertaken to see if having a technetium-99m sulfur colloid liver-spleen scan to compare with the /sup 111/In leukocyte scan would improve the reader's ability to diagnose or exclude upper abdominal abscesses. Ninety patients with suspected upper abdominal abscesses were examined with /sup 111/In leukocyte scans followed immediately by conventional /sup m99/Tc sulfur colloid liver-spleen scans in the same projections. In 57% of patients with upper abdominal abscesses and 25% of all patients studied, the /sup 99m/Tc sulfur colloid scan was essential to diagnose or exclude an upper abdominal abscess. The liver-spleen scan was considered helpful in another 13%. The addition of a /sup 99m/Tc sulfur colloid liver-spleen scan to the /sup 111/In leukocyte study is useful when evaluating patients with suspected upper abdominal abscesses.

  4. 111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content.

    PubMed

    Blocklet, Didier; Toungouz, Michel; Kiss, Robert; Lambermont, Micheline; Velu, Thierry; Duriau, Dominique; Goldman, Michel; Goldman, Serge

    2003-03-01

    In cancer vaccination trials, antigen-loaded dendritic cells (DCs) are usually injected intradermally and are expected to rapidly move to a regional lymph node where antigen presentation should occur. In this study we investigated the influence of indium-111 oxine (111In) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling on the motility and actin content of antigen-loaded DCs in parallel with in vivo migration in humans. Human autologous monocyte-derived DCs loaded with a tumour antigen were labelled with 111In (0.11, 0.37 or 0.74 MBq/10(7) DCs) or 99mTc-HMPAO (18.5 or 185 MBq/10(7) DCs). 111In labelling was much more stable than 99mTc-HMPAO labelling. Quantitative videomicroscopy showed that the mean distance of displacement of DCs increased in accordance with the 111In activity used for labelling. Monomeric (G) and filamentous (F) actin content of DCs evaluated by quantitative immunofluorescence demonstrated that the ratio of filamentous to globular actin content in labelled DCs increased significantly in accordance with the activity used for labelling with both tracers. Twelve patients enrolled in a phase I/II vaccination trial received injections of 10(7) antigen-loaded DCs labelled with either 0.74 MBq of 111In (group A, n=6/12) or 18.5 MBq of 99mTc-HMPAO (group B, n=6/12) in the proximal part of the legs, one intradermally on one side, one subcutaneously on the opposite side. In three of the six patients of each group, antigen-loaded DCs were incubated with monophosphoryl lipid A (MPL) just before the labelling, in order to initiate the maturation process (subgroup MPL+). Only one MPL+ patient of group A exhibited faint focal uptake in the inguinal region on the late images. Group B presented a more complex pattern of radioactivity distribution (early bladder activity without brain uptake) indicating that 99mTc-HMPAO is not a suitable radiopharmaceutical for labelling of loaded DCs. The activity cleared from DCs as a labelled molecule

  5. Shiga toxin-producing Escherichia coli O157, O26 and O111 in cattle faeces and hides in Italy

    PubMed Central

    Bonardi, S.; Alpigiani, I.; Tozzoli, R.; Vismarra, A.; Zecca, V.; Greppi, C.; Bacci, C.; Bruini, I.; Brindani, F.

    2015-01-01

    Introduction Ruminants are regarded as the natural reservoir for Shiga toxin-producing Escherichia coli (STEC), especially of serogroup O157. Materials and methods During 2011 and 2012, 320 samples (160 faecal samples from the rectum and 160 hide samples from the brisket area) were collected from 160 cattle at slaughter in Northern Italy during warm months (May to October). Cattle were reared in different farms and their age at slaughter ranged between nine months and 15 years, most of them being culled cattle (median age: six years; average age: 4.6 years). Samples were tested by immunomagnetic-separation technique for E coli O157 and O26 and by a screening PCR for stx genes followed by cultural detection of STEC. The virulence genes stx1, stx2, eae, and e-hlyA were detected and among stx2-positive isolates the presence of the stx2a and stx2c variants was investigated. Results Twenty-one of 160 cattle (13.1 per cent; 95 per cent CI 8.3 to 19.4 per cent) were found to be faecal carriers of STEC. STEC O157 was found in 10 (6.3 per cent) samples, STEC O26 in six (3.8 per cent) and STEC O111 in one (0.6 per cent). Four isolates (2.5 per cent) were O not determined (OND). Six out of 160 (3.8 per cent; 95 per cent CI 1.4 to 8.0 per cent) hide samples were positive for STEC; four hides (2.5 per cent) were contaminated by STEC O157 and two (1.3 per cent) by STEC O26. In three cattle (1.9 per cent) STEC from both faeces and hides were detected. Among STEC O157, 87.5 per cent of them carried the stx2c gene and 12.5 per cent carried both stx1 and stx2c genes. No O157 isolate harboured stx2a variant. STEC O26 and O111 carried the stx1 gene only. One OND strain carried both the stx2a and stx2c genes. Conclusions This study shows that STEC O157 from cattle can harbour the stx2c variant, which is associated with haemolytic uraemic syndrome in humans, and that cattle hides may be a source of human pathogenic STEC O157 and O26 in the slaughterhouse environment. PMID:26392887

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

    PubMed

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

    2016-04-01

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

  7. Near-Infrared-Emitting BODIPY-trisDOTA(111) In as a Monomolecular Multifunctional Imaging Probe: From Synthesis to In Vivo Investigations.

    PubMed

    Maindron, Nicolas; Ipuy, Martin; Bernhard, Claire; Lhenry, Damien; Moreau, Mathieu; Carme, Sabin; Oudot, Alexandra; Collin, Bertrand; Vrigneaud, Jean-Marc; Provent, Peggy; Brunotte, François; Denat, Franck; Goze, Christine

    2016-08-26

    A new generation of monomolecular imaging probes (MOMIP) based on a distyryl-BODIPY (BODIPY=boron-dipyrromethene) coupled with three DOTA macrocycles has been prepared (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The MOMIP presents good fluorescence properties and is very stable in serum. The bimodal probe was conjugated to trastuzumab, and an optical in vivo study showed high accumulation of the imaging agent at the tumor site. (111) In radiometallation of the bioconjugate was performed in high radiochemical yield, highlighting the potential of this new BODIPY-chelators derivative as a bimodal imaging probe. PMID:27410465

  8. 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.

  9. 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

  10. 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.

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

    SciTech Connect

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

    1990-03-01

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

  12. 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.

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2005-01-01

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

  15. 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.

  16. 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.

  17. Radiometals as payloads for radioimmunotherapy for lymphoma.

    PubMed

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

    2004-10-01

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

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

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

  19. 68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT.

    PubMed

    Breer, Stefan; Brunkhorst, Thomas; Beil, F Timo; Peldschus, Kersten; Heiland, Max; Klutmann, Susanne; Barvencik, Florian; Zustin, Jozef; Gratz, Klaus-Friedrich; Amling, Michael

    2014-07-01

    Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. However, recent studies revealed that still a large number of tumors remained undetected by octreotide imaging. Hence, studies focused on different SSTR imaging methods such as 68Ga DOTA-NOC, 68Ga DOTA-TOC and 68Ga DOTA-TATE PET/CT with promising first results. Studies comparing different SSTR imaging methods for tumor localization in TIO are rare and thus little is known about diagnostic alternatives once a particular method failed to detect a tumor in patients with TIO. Here, we report the data of 5 consecutive patients suffering from TIO, who underwent both 111Indium-octreotide scintigraphy (111In-OCT) SPECT/CT as well as 68Ga DOTA-TATE PET/CT for tumor detection. While 111In-OCT SPECT/CT allowed tumor detection in only 1 of 5 patients, 68Ga DOTA-TATE PET/CT was able to localize the tumor in all patients. Afterwards, anatomical imaging of the region of interest was performed with CT and MRI. Thus, successful surgical resection of the tumor was achieved in all patients. Serum phosphate levels returned to normal and all patients reported relief of symptoms within weeks. Moreover, an iliac crest biopsy was obtained from every patient and revealed marked osteomalacia in all cases. Follow-up DXA revealed an increase in BMD of up to 34.5% 1-year postoperative, indicating remineralization. No recurrence was observed. In conclusion our data indicates that 68Ga DOTA-TATE PET/CT is an effective and promising diagnostic tool in the diagnosis of TIO, even in patients in whom 111In-OCT prior failed to detect

  20. 68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT.

    PubMed

    Breer, Stefan; Brunkhorst, Thomas; Beil, F Timo; Peldschus, Kersten; Heiland, Max; Klutmann, Susanne; Barvencik, Florian; Zustin, Jozef; Gratz, Klaus-Friedrich; Amling, Michael

    2014-07-01

    Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. However, recent studies revealed that still a large number of tumors remained undetected by octreotide imaging. Hence, studies focused on different SSTR imaging methods such as 68Ga DOTA-NOC, 68Ga DOTA-TOC and 68Ga DOTA-TATE PET/CT with promising first results. Studies comparing different SSTR imaging methods for tumor localization in TIO are rare and thus little is known about diagnostic alternatives once a particular method failed to detect a tumor in patients with TIO. Here, we report the data of 5 consecutive patients suffering from TIO, who underwent both 111Indium-octreotide scintigraphy (111In-OCT) SPECT/CT as well as 68Ga DOTA-TATE PET/CT for tumor detection. While 111In-OCT SPECT/CT allowed tumor detection in only 1 of 5 patients, 68Ga DOTA-TATE PET/CT was able to localize the tumor in all patients. Afterwards, anatomical imaging of the region of interest was performed with CT and MRI. Thus, successful surgical resection of the tumor was achieved in all patients. Serum phosphate levels returned to normal and all patients reported relief of symptoms within weeks. Moreover, an iliac crest biopsy was obtained from every patient and revealed marked osteomalacia in all cases. Follow-up DXA revealed an increase in BMD of up to 34.5% 1-year postoperative, indicating remineralization. No recurrence was observed. In conclusion our data indicates that 68Ga DOTA-TATE PET/CT is an effective and promising diagnostic tool in the diagnosis of TIO, even in patients in whom 111In-OCT prior failed to detect

  1. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1997-01-01

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

  5. AFTI F-111 in flight

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  6. AFTI F-111 in flight

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  7. /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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

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

    PubMed

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

    2014-01-01

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

  10. 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

  11. 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

  12. 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. PMID:26930130

  13. 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.

  14. 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

  15. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods

    NASA Astrophysics Data System (ADS)

    He, Bin; Frey, Eric C.

    2010-06-01

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

  16. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods.

    PubMed

    He, Bin; Frey, Eric C

    2010-06-21

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

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

    PubMed

    Malmberg, Jennie; Tolmachev, Vladimir; Orlova, Anna

    2011-04-01

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

  18. MicroSPECT/CT imaging of primary human AML engrafted into the bone marrow and spleen of NOD/SCID mice using 111In-DTPA-NLS-CSL360 radioimmunoconjugates recognizing the CD123+ / CD131- epitope expressed by leukemia stem cells.

    PubMed

    Leyton, Jeffrey V; Williams, Brent; Gao, Catherine; Keating, Armand; Minden, Mark; Reilly, Raymond M

    2014-11-01

    Engraftment of primary human acute myeloid leukemia (AML) specimens into the bone marrow (BM) of NOD/SCID mice has been used to study leukemia biology and new treatments for the disease. CSL360 is a chimeric IgG1 monoclonal antibody that recognizes CD123 (IL-3 receptor α-subchain) expressed in the absence of CD131 (β-subchain), an epitope that is displayed by leukemia stem cells (LSCs). We are studying CSL360 modified with diethylenetriaminepentaacetic acid (DTPA) for complexing 111In and 13-mer nuclear translocation sequence (NLS) peptides to enable nuclear importation in LSCs for Auger electron radioimmunotherapy (RIT) of AML. We demonstrate that microSPECT/CT imaging using 111In-DTPA-NLS-CSL360 revealed engraftment of primary human AML specimens into the BM and spleen of NOD/SCID mice. Our results suggest that microSPECT/CT imaging is a powerful tool which enables non-invasive assessment of the engraftment of AML into NOD/SCID mice and in the current study specifically probes an epitope displayed by the LSC subpopulation. The targeting of 111In-DTPA-NLS-CSL360 to sites of AML engraftment in the NOD/SCID mouse model is encouraging for future RIT studies. Ultimately, SPECT imaging could be applied in AML patients to assess the delivery of 111In-DTPA-NLS-CSL360 to sites of leukemia and be combined with Auger electron RIT using the same agent targeting the LSC population as a "theranostic" pair.

  19. Radioimmunoconjugates for the treatment of cancer.

    PubMed

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

    2014-10-01

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

  20. Current Status of Allogeneic transplantation for Aggressive Non-Hodgkin lymphoma

    PubMed Central

    van Besien, Koen

    2016-01-01

    Purpose To provide a succinct update on the role of allogeneic stem cell transplantation in the management of patients with aggressive lymphomas. To clarify the indications for allogeneic transplantation vis-à-vis autologous transplant and to discuss the rational and potential benefits of reduced intensity conditioning(RIC), non-myeloablative (NMA) transplant, T-cell depletion and variations in GVHD prophylaxis. Recent findings Considerable effort has been spent in developing transplant regimens with reduced toxicity and reduced GVHD. The role of allogeneic transplantation has also been redefined in light of advances in lymphoma classification, diagnostic methods, particularly PET scan and advances in transplant technology. Haplo and UCB SCT allow identification of a donor for nearly all patients. Summary RIC and NMA conditioning have reduced early toxicity but are associated with increased risk for disease recurrence. Promising data have been reported from a novel conditioning regimen combining NMAwith ibritumomab tiuxetan. T-cell depletion reduces cGVHD but has some increase in rate of recurrence. Rapamycin may be associated with reduction in risk for disease recurrence. In diffuse large B cell lymphoma, the outcome of allo SCT depends on patient characteristics and chemosensitivity. It is seful after failure of autoSCT and in partial responses to salvage therapy. Allo SCT may be the treatment of choice for advanced T-cell and NK cell lymphoma and for ATLL. Prophylactic or preemptive DLI may be useful, but requires controlled studies. PMID:21946246

  1. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

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

  2. 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.

  3. Gateways to clinical trials.

    PubMed

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

    2006-04-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have 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: ABT-510, adalimumab, alefacept, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate. PMID:16810345

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

    PubMed

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

    2004-12-01

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

  5. 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.

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

    PubMed

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

    2015-07-01

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

  7. 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.

  8. Gateways to clinical trials.

    PubMed

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

    2007-10-01

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

  9. Gateways to clinical trials.

    PubMed

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

    2004-10-01

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

  10. A Phase II Trial of R-CHOP Followed by Radioimmunotherapy for Early Stage (Stages I/II) Diffuse Large B-Cell Non-Hodgkin Lymphoma: ECOG3402

    PubMed Central

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

    2015-01-01

    Summary Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional CR rate of ≥75% to RCHOP and 90Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4–6 cycles of RCHOP followed by RIT (0.4 mCi/kg); patients with PET positive sites of disease after RCHOP/RIT received 30Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/CRu. Forty–eight patients proceeded to RIT and one patient in PR after RIT received IFRT and achieved a CR. The best response after RCHOP+RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% CI:77–96%). With a median follow-up of 5.9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine% of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  11. [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.

  12. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

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

  13. Gateways to clinical trials.

    PubMed

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

    2004-10-01

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

  14. Gateways to clinical trials.

    PubMed

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

    2006-01-01

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

  15. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

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

  16. Gateways to clinical trials.

    PubMed

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

    2006-09-01

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

  17. 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

  18. Therapeutic Potential of 90Y- and 131I-Labeled Anti-CD20 Monoclonal Antibody in Treating Non-Hodgkin's Lymphoma with Pulmonary Involvement: A Monte Carlo–Based Dosimetric Analysis

    PubMed Central

    Song, Hong; Du, Yong; Sgouros, George; Prideaux, Andrew; Frey, Eric; Wahl, Richard L.

    2010-01-01

    Pulmonary involvement is common in patients with non-Hodgkin's lymphoma (NHL). 90Y- and 131I-anti-CD20 antibodies (ibritumomab tiuxetan and tositumomab, respectively) have been approved for the treatment of refractory low-grade follicular NHL. In this work, we used Monte Carlo–based dosimetry to compare the potential of 90Y and 131I, based purely on their emission properties, in targeted therapy for NHL lung metastases of various nodule sizes and tumor burdens. Methods Lung metastases were simulated as spheres, with radii ranging from 0.2 to 5.0 cm, which were randomly distributed in a voxelized adult male lung phantom. Total tumor burden was varied from 0.2 to 1,641 g. Tumor uptake and retention kinetics of the 2 radionuclides were assumed equivalent; a uniform distribution of activity within tumors was assumed. Absorbed dose to tumors and lung parenchyma per unit activity in lung tumors was calculated by a Monte Carlo–based system using the MCNP4B package. Therapeutic efficacy was defined as the ratio of mean absorbed dose in the tumor to that in normal lung. Dosimetric analysis was also performed for a lung-surface distribution of tumor nodules mimicking pleural metastatic disease. Results The therapeutic efficacy of both 90Y and 131I declined with increasing tumor burden. In treating tumors with radii less than 2.0 cm, 131I targeting was more efficacious than 90Y targeting. 90Y yielded a broader distribution of tumor absorbed doses, with the minimum 54.1% lower than the average dose; for 131I, the minimum absorbed dose was 33.3% lower than the average. The absorbed dose to normal lungs was reduced when the tumors were distributed on the lung surface. For surface tumors, the reductions in normal-lung absorbed dose were greater for 90Y than for 131I, but 131I continued to provide a greater therapeutic ratio across different tumor burdens and sizes. Conclusion Monte Carlo–based dosimetry was performed to compare the therapeutic potential of 90Y and 131I

  19. Evaluation of quantitative 90Y SPECT based on experimental phantom studies

    NASA Astrophysics Data System (ADS)

    Minarik, D.; Sjögreen Gleisner, K.; Ljungberg, M.

    2008-10-01

    In SPECT imaging of pure beta emitters, such as 90Y, the acquired spectrum is very complex, which increases the demands on the imaging protocol and the reconstruction. In this work, we have evaluated the quantitative accuracy of bremsstrahlung SPECT with focus on the reconstruction algorithm including model-based attenuation, scatter and collimator-detector response (CDR) compensations. The scatter and CDR compensation methods require pre-calculated point-spread functions, which were generated with the SIMIND MC program. The SIMIND program is dedicated for simulation of scintillation camera imaging and only handles photons. The aim of this work was therefore twofold. The first aim was to implement simulation of bremsstrahlung imaging into the SIMIND code and to validate simulations against experimental measurements. The second was to investigate the quality of bremsstrahlung SPECT imaging and to evaluate the possibility of quantifying the activity in differently shaped sources. In addition, a feasibility test was performed on a patient that underwent treatment with 90Y-Ibritumomab tiuxetan (Zevalin®). The MCNPX MC program was used to generate bremsstrahlung photon spectra which were used as source input in the SIMIND program. The obtained bremsstrahlung spectra were separately validated by experimental measurement using a HPGe detector. Validation of the SIMIND generated images was done by a comparison to gamma camera measurements of a syringe containing 90Y. Results showed a slight deviation between simulations and measurements in image regions outside the source, but the agreement was sufficient for the purpose of generating scatter and CDR kernels. For the bremsstrahlung SPECT experiment, the RSD torso phantom with 90Y in the liver insert was measured with and without background activities. Projection data were obtained using a GE VH/Hawkeye system. Image reconstruction was performed by using the OSEM algorithm with and without different combinations of model

  20. Gateways to clinical trials.

    PubMed

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

    2006-10-01

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

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

    PubMed

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

    2015-06-01

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

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

    SciTech Connect

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

    2002-01-01

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

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

    PubMed

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

    2015-07-01

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

  4. 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.

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

    PubMed

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

    2015-01-26

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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  7. Surface topographical changes on Pt(100) and Pt(111) in the NO + CO reaction: a reflection electron microscopy study

    NASA Astrophysics Data System (ADS)

    Uchida, Y.; Imbihl, R.; Lehmpfuhl, G.

    1992-09-01

    The structural modifications which are induced by the NO + CO reaction on Pt surfaces were studied using reflection electron microscopy (REM) to image atomic steps. Small single crystal spheres of Pt (diameter ≈ 0.3 mm) were prepared and then exposed in a UHV chamber to a flow of CO and NO at 10 -6 Torr. The sample temperature was cycled between 300 and 700 K over an exposure time of typically ˜ 1 h. On the (100) orientations, the reaction led to a strong roughening of the substrate and to the development of a domain structure. As was demonstrated in adsorption experiments with CO (NO) alone, the major contribution to the roughening originated from the 1 × 1 ⇄ hex phase transition of Pt(100). On the (111) facets the flat terraces were only weakly affected by the reaction, but the step edges were quite strongly attacked leading to a meandering of the initially straight step edges. The observations made on Pt(111) are consistent with a mechanistic picture in which the NO + CO reaction takes entirely place at step and kink sites.

  8. 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.

  9. Adsorption behaviors of monomer and dimer of formic acid on Pt(111) in the absence and presence of water.

    PubMed

    Qi, Yuanyuan; Zhu, Rongxiu; Zhang, Dongju

    2014-06-01

    By performing density functional theory (DFT) theory calculations, we studied the adsorption behaviors of the monomer and dimer of formic acid (HCOOH, FA) on the Pt(111) surface with and without the presence of water molecules. The monomer prefers to stand on the surface of Pt(111), and in the most stable adsorption configuration the carbonyl O of HCOOH binds to the atop site of a Pt atom and the hydroxyl H points asymmetrically to two neighboring Pt atoms. The dimer of HCOOH not only exists in the gas-phase but also on Pt(111) surface, and the eight-membered ring dimer is identified as the energetically most favorable dimeric structure of HCOOH both in gas-phase and on Pt(111) surface. With the presence of water molecules, both the monomer and dimer of HCOOH prefer to lie parallel to the surface so as to maximize the number of H-bonds to adjacent water molecules. These results indicate that water molecules significantly influence the initial adsorption manner of HCOOH and further its decomposition reactivity on Pt(111) surface. The present work shows the adsorption behavior of HCOOH dimer on Pt(111) for the first time and also gives several new adsorption configurations of the monomer that are not reported in literature. The theoretical results are expected to provide a valuable input to understand the reactivity of HCOOH on Pt(111). PMID:24827612

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

    SciTech Connect

    arenz@thch.uni-bonn.de

    2002-10-01

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

  11. 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.

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

    PubMed

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

    2016-07-20

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

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

    PubMed

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

    1999-09-01

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

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

    PubMed

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

    2000-10-01

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

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

    PubMed

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

    2000-09-01

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

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

    PubMed

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

    1998-01-01

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

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

    SciTech Connect

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

    1995-10-01

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

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

    PubMed

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

    2016-07-20

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

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

    USGS Publications Warehouse

    Ball, Maria H.; Schaffranek, Raymond W.

    2000-01-01

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

  20. Reactive molecular dynamics of the initial oxidation stages of Ni111 in pure water: effect of an applied electric field.

    PubMed

    Assowe, O; Politano, O; Vignal, V; Arnoux, P; Diawara, B; Verners, O; van Duin, A C T

    2012-12-01

    Corrosion processes occurring in aqueous solutions are critically dependent upon the interaction between the metal electrode and the solvent. In this work, the interaction of a nickel substrate with water molecules has been investigated using reactive force field (ReaxFF) molecular dynamics simulations. This approach was originally developed by van Duin and co-workers to study hydrocarbon chemistry and the catalytic properties of organic compounds. To our knowledge, this method has not previously been used to study the corrosion of nickel. In this work, we studied the interaction of 480 molecules of water (ρ = 0.99 g·cm(-3)) with Ni(111) surfaces at 300 K. The results showed that a water "bilayer" was adsorbed on the nickel surface. In the absence of an applied electric field, no dissociation of water was observed. However, the nickel atoms at the surface were charged positively, whereas the first water layer was charged negatively, indicating the formation of an electric double layer. To study the corrosion of nickel in pure water, we introduced an external electric field between the metal and the solution. The electric field intensity varied between 10 and 20 MeV/cm. The presence of this electric field led to oxidation of the metal surface. The structural and morphological differences associated with the growth of this oxide film in the presence of the electric field were evaluated. The simulated atomic trajectories were used to analyze the atomic displacement during the reactive process. The growth of the oxide scale on the nickel surface was primarily due to the movement of anions toward the interior of the metal substrate and the migration of nickel toward the free surface. We found that increasing the electric field intensity sped up the corrosion of nickel. The results also showed that the oxide film thickness increased linearly with increasing electric field intensity.

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  4. 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.

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

    PubMed

    Kovalev, G I; Vorob'ev, V V

    2002-01-01

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

  6. Biodistribution and tumor localization of 111In-labeled unmodified and modified F(ab')2 fragments of human monoclonal IgM (16.88) in a nude mouse model.

    PubMed

    Quadri, S M; Siddiqui, A; Klein, J L; Vriesendorp, H M

    1995-05-01

    Unmodified F(ab')2 and modified Fab'-BMH-Fab' fragments of human monoclonal IgM (16.88) were compared for biodistribution and tumor localization in nude mice bearing LS-174T human colon carcinoma xenografts. Although both unmodified and modified fragments of IgM cleared rapidly from the blood, the radioactivity retentions for each fragment in liver and kidney were significantly different. Kidney uptake of the modified fragment was about 4-fold lower than kidney uptake of the unmodified fragment. Radioactivity uptake in liver was 2-4-fold higher for the modified fragment. Lower liver and higher kidney uptake of unmodified fragments reflected the labile disulfide linkage of F(ab')2 in their hinge region and the subsequent behavior of the Fab' fragments resulting from the reduction of the disulfide linkage. Higher liver and lower kidney retention of modified fragments, on the other hand, resulted from the different cleavage mechanism of the stable thioether linkage. Tumor targeting was similar for unmodified and modified fragments at approx. 4% of injected dose per gram. These results indicate that the changes in fragment linkage chemistry may provide different pharmacokinetic patterns in vivo and improve the therapeutic application of radiolabeled fragments in human patients.

  7. 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.

  8. Accumulation of sup 111 In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo. Inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognizing the CD18 antigen

    SciTech Connect

    Nourshargh, S.; Rampart, M.; Hellewell, P.G.; Jose, P.J.; Harlan, J.M.; Edwards, A.J.; Williams, T.J. )

    1989-05-01

    The mAb 60.3 recognizes the neutrophil CD18 Ag. We have investigated the effect of in vitro pretreatment of radiolabeled neutrophils with mAb 60.3 on their accumulation in vivo. Further, we have compared the in vivo effects of mAb 60.3 with its effects on neutrophil adherence in vitro. Neutrophil accumulation in vivo was measured in response to: (1) exogenous mediators FMLP, C5a des Arg, LTB4 and IL-1; (2) endogenous mediators generated in a non-allergic inflammatory reaction induced by zymosan; and (3) endogenous mediators generated in two allergic inflammatory reactions, a passive cutaneous anaphylactic reaction and a reversed passive Arthus reaction in rabbit skin. Pretreatment of neutrophils with mAb 60.3 inhibited their accumulation in all the responses. The results demonstrate that there is a common mechanism mediating neutrophil accumulation in these inflammatory reactions. Neutrophils pretreated with mAb 60.3 were also unresponsive to chemoattractants in in vitro adherence assays. However, the antibody-treated neutrophils responded normally to FMLP and C5a with respect to granular enzyme release. These results suggest that the basal expression of CD18 Ag is important for the adherence of neutrophils to microvascular endothelial cells stimulated by the local generation, or administration, of chemical mediators in vivo. Despite the fact that mediators such as FMLP can increase CD18 expression in vitro, it appears more likely that such mediators act in vivo by inducing a conformational change in the basally expressed neutrophil adhesive molecules.

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

    SciTech Connect

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

    1988-10-01

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

  10. Comparison of oxine and tropolone methods for labeling human platelets with indium-111

    SciTech Connect

    Kotze, H.F.; Heyns, A.D.; Loetter, M.G.P.; Pieters, H.; Roodt, J.P.; Sweetlove, M.A.; Badenhorst, P.N. )

    1991-01-01

    The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-({sup 111}In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with {sup 111}In-oxine or in plasma with {sup 111}In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of {sup 111}In-oxine and {sup 111}In-tropolone did not differ, and the mean platelet lifespan was also similar ({sup 111}In-oxine: 230 +/- 29 hr; {sup 111}In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, {sup 111}In-oxine and {sup 111}In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with {sup 111}In-oxine or {sup 111}In-tropolone do not differ significantly.

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

    PubMed

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

    2016-02-01

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

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

    SciTech Connect

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

    1986-04-01

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

  13. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  14. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  15. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  16. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  17. 49 CFR 393.80 - Rear-vision mirrors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  18. 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.

  19. 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.

  20. Differences in biodistribution of indium-111-and iodine-131-labeled B72. 3 monoclonal antibodies in patients with colorectal cancer

    SciTech Connect

    Yokoyama, K.; Carrasquillo, J.A.; Chang, A.E.; Colcher, D.; Roselli, M.; Sugarbaker, P.; Sindelar, W.; Reynolds, J.C.; Perentesis, P.; Gansow, O.A.

    1989-03-01

    We have compared the biodistributions of (/sup 131/I)B72.3 and /sup 111/In-SCN-Bz-DTPA B72.3 monoclonal antibody (MoAb) in patients with metastatic colon cancers. B72.3 is an IgG1 that recognizes a mucin-like colon cancer associated antigen. Eight patients were infused with 3-5 mCi and 0.36-20 mg of /sup 111/In-labeled B72.3 prepared with a bifunctional chelate, isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA). The biodistribution was compared with that of 13 patients previously studied as part of a separate trial, with 1-10 mCi and 0.16-1.35 mg of (/sup 131/I)B72.3. The Beta T1/2 in serum was 63 +/- 5 hr for 111In-SCN-Bz-DTPA B72.3 and 52 +/- 10 hr for (/sup 131/I)B72.3. Whole-body retention of the /sup 111/In (T1/2 = 11.8 days) was significantly longer than for (/sup 131/I)B72.3 (T1/2 = 3.3 days), p less than 0.000001. The /sup 131/I was excreted primarily through the urine. Urinary excretion of /sup 111/In was low and gamma camera images confirmed that some /sup 111/In was excreted in the bowel. Tumor localization was seen in one of seven evaluable patients receiving /sup 111/In-SCN-Bz-DTPA B72.3. Gamma camera images showed that the liver concentrates /sup 111/In but not /sup 131/I. We conclude that /sup 111/In-SCN-Bz-DTPA B72.3 is metabolized in a different manner from the iodinated B72.3. The high concentration and prolonged retention of /sup 111/In by the liver interferes with tumor imaging of metastases.

  1. Molecular Imaging of Bcr-Abl Phosphokinase in a Xenograft Model*

    PubMed Central

    Wu, Ji Yuan; Yang, David J.; Angelo, Laura S.; Kohanim, Saady; Kurzrock, Razelle

    2009-01-01

    The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by gamma imaging using an 111Indium-labeled anti-phosphotyrosine antibody, and if the response to treatment with imatinib could be detected using this imaging technique. Anti-phosphotyrosine antibody (APT) was labeled with indium (111In) using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a non-receptor tyrosine kinase, xenografts of the human chronic myelogenous leukemia (CML) cell line K562 were used. Gamma scintigraphy of the tumor-bearing mice, before and after imatinib treatment, was obtained 1, 24, and 48 hours after they were given 111In-EC-APT (100 uCi/mouse, i.v.). 111In-EC-APT is preferentially taken up by Bcr-Abl-bearing tumor cells when compared to 111In-EC-BSA or 111In-EC-IgG1 controls, and comparable to the level of uptake of 111In-EC-Bcr-Abl. Imatinib treatment resulted in decreased expression of phosphorylated Bcr-Abl by Western blot analysis, which correlated with early (four days after starting imatinib) kinase down-regulation as assessed by imaging using 111In-EC-APT. The optimal time to imaging was 24 and 48 hours after injection of 111In-EC-APT. Although tumor regression was insignificant on day 4 after starting imatinib treatment, it was marked by day 14. 111In-EC-APT can assess intracellular phosphokinase activity, and down-regulation of phosphokinase activity predates tumor regression. This technique may therefore be useful in the clinic to detect the presence of phosphokinase activity, and for early prediction of response. PMID:19258427

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

    SciTech Connect

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

    1994-11-01

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

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

    SciTech Connect

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

    1986-05-01

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

  4. 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.

  5. An experimental comparison of radioactive labels with potential application to lymphocyte migration studies in patients.

    PubMed Central

    Rannie, G H; Thakur, M L; Ford, W L

    1977-01-01

    The suitability of two radionuclides (99mTc, 111In) for labelling lymphocytes have been evaluated in rats by comparison with a standard method using 51Cr. For the study of lymphocyte migration in patients labelling with 111In-labelled oxine is clearly the most promising because both in vivo and in vitro it remains associated with lymphocytes and the labelled cells migrate normally into lymphoid tissues. The physical characteristics of 111In are also favourable. Not only does 99mTc rapidly dissociate from lymphocytes but also it compromises their ability to recirculate from blood to lymph. PMID:589868

  6. Diagnostic value of bone marrow imaging with /sup 111/indium-transferrin and /sup 99m/technetium-colloids in myelofibrosis

    SciTech Connect

    Arrago, J.P.; Rain, J.D.; Vigneron, N.; Poirier, O.; Chomienne, C.; D'Agay, M.F.; Najean, Y.

    1985-03-01

    /sup 111/Indium--transferrin (/sup 111/In) and /sup 99m/Technetium-colloids (/sup 99m/Tc) bone marrow imaging of 55 myelofibrosis (MF) cases has been compared with clinical, histological, and iron-kinetics data. The best correlations are seen between the splenic uptake of /sup 111/In with the spleen/sacrum ratio of /sup 59/Fe at the first hour and also with the splenic erythropoiesis histologically assessed in ten splenectomized patients. Moreover, sacrum uptake of /sup 111/In, when compared with sacrum uptake of /sup 59/Fe and with hematopoietic cellularity of the bone marrow reflects faithfully the hematopoietic cell content of the marrow. Thus, /sup 111/In bone marrow imaging provides a noninvasive and useful tool for the diagnosis of myeloid metaplasia in MF. Ferrokinetic studies still appreciate with better insight the amount of ineffective erythropoiesis or hemolysis and remain therefore of great value when splenectomy is discussed.

  7. Indium-111 WBC detection of emphysematous gastritis in pancreatitis

    SciTech Connect

    Caruana, V.; Swayne, L.C.; Salaki, J.S. )

    1990-01-01

    We present a case of emphysematous gastritis initially detected with 111In oxine-labeled white blood cell scintigraphy and subsequently confirmed by computed tomography. Early aggressive antibiotic and supportive therapy resulted in a successful clinical outcome.

  8. 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.

  9. Acute effects of radiation therapy on indium-111-labeled leukocyte uptake in bone marrow

    SciTech Connect

    Palestro, C.J.; Kim, C.K.; Vega, A.; Goldsmith, S.J. )

    1989-11-01

    We recently performed ({sup 99m}Tc)MDP bone and {sup 111}In-labeled leukocyte scintigraphy on a patient receiving radiation therapy to the lower cervical and upper thoracic spine. While the bone images revealed only minimally increased activity in the radiation port, leukocyte images revealed diffuse, intensely increased uptake in this same region. Radiation therapy should be included in the differential diagnosis of increased bone marrow activity on {sup 111}In leukocyte images.

  10. Critical behavior in radiation damaged systems

    NASA Astrophysics Data System (ADS)

    Arends, A. R.; Hohenemser, C.; Suter, R. M.

    1980-09-01

    Perturbed angular distribution (PAD) measurements of Bleck et al. of the critical behavior of63Ni Ni,66Cu Ni, and67Zn Ni have been reanalyzed, and shown to be insufficiently asymptotic to permit deduction of meaningful critical exponents. Via experiments on implanted111In Ni, done with and without annealing of radiation damage, and by comparison to diffused111In Ni, it is suggested that unannealed radiation damage can produce serious systematic errors in critical exponents.

  11. 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.

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

    SciTech Connect

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

    1987-07-01

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

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

    SciTech Connect

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

    1990-03-01

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

  14. New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation.

    PubMed

    Subramanian, R; Colony, J; Shaban, S; Sidrak, H; Haspel, M V; Pomato, N; Hanna, M G; McCabe, R P

    1992-01-01

    111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3-bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies.

  15. Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging

    SciTech Connect

    Johnson, J.A.; Christie, M.J.; Sandler, M.P.; Parks, P.F. Jr.; Homra, L.; Kaye, J.J.

    1988-08-01

    Preoperative exclusion or confirmation of periprosthetic infection is essential for correct surgical management of patients with suspected infected joint prostheses. The sensitivity and specificity of (/sup 111/In)WBC imaging in the diagnosis of infected total joint prostheses was examined in 28 patients and compared with sequential (/sup 99m/Tc)HDP/(/sup 111/In)WBC scintigraphy and aspiration arthrography. The sensitivity of preoperative aspiration cultures was 12%, with a specificity of 81% and an accuracy of 58%. The sensitivity of (/sup 111/In)WBC imaging alone was 100%, with a specificity of 50% and an accuracy of 65%. When correlated with the bone scintigraphy and read as sequential (/sup 99m/Tc)HDP/(/sup 111/In)WBC imaging, the sensitivity was 88%, specificity 95%, and accuracy 93%. This study demonstrates that (/sup 111/In)WBC imaging is an extremely sensitive imaging modality for the detection of occult infection of joint prostheses. It also demonstrates the necessity of correlating (/sup 111/In)WBC images with (/sup 99m/Tc)HDP skeletal scintigraphy in the detection of occult periprosthetic infection.

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

    PubMed

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

    2016-03-01

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

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

    SciTech Connect

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

    1983-05-01

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

  18. Cardiac and vascular imaging with labeled platelets and leukocytes

    SciTech Connect

    Dewanjee, M.K.

    1984-07-01

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

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

    SciTech Connect

    Terry, Samantha Y.A.

    2012-07-15

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

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

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

    1990-07-01

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

  2. Search for magnetic interaction in In doped AlN using perturbed angular correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Agarwal, Ishita; Kessler, Patrick; Vianden, Reiner

    2013-05-01

    The possible presence of a large magnetic field due to spin polarization of a Cd nucleus (decay product of 111In) at an Al substitutional site in AlN is investigated with perturbed angular correlation (PAC) spectroscopy. The PAC spectra of 111In/111Cd in AlN show two probe environments: a weak quadrupole interaction (quadrupole interaction constant, ν _Q^{ lattice} = 30 MHz) due to 111In probes at a defect free Al substitutional site and an unknown large interaction (ν _Q^{ complex} = 300 MHz) tentatively attributed to a nearest neighbour pair between 111In and a nitrogen vacancy (VN) aligned along the c-axis. Surprisingly, in density functional theory (DFT) calculations, such a large electric field gradient (EFG) could not be reproduced. However, an inclusion of spin polarization in the calculations indicates a strong magnetic field at 50 % of the 111In/111Cd site. An attempt to verify the presence of the strong magnetic field and to explain the origin of the strong interaction is made. Orientation measurements show, the large interaction is not characterised by a magnetic interaction and is predominantly due to the EFG. However, in the presence of an external magnetic field, the strong interaction probe environment becomes more uniform and the EFG increases by 10 %. This definitely hints towards some sort of magnetic interaction at the strong interaction probe site.

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

    PubMed

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

    1988-10-01

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

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

    PubMed

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

    2012-09-10

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

  5. 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.

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

    SciTech Connect

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

    1988-10-01

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

  7. Identification and treatment of cyclosporine-associated allograft thrombosis

    SciTech Connect

    Schlanger, R.E.; Henry, M.L.; Sommer, B.G.; Ferguson, R.M.

    1986-08-01

    Endothelial injury associated with cyclosporine (CSA) therapy in the absence of rejection has resulted in irreversible intrarenal allograft thrombosis and transplant loss. Indium 111 (/sup 111/In)-labeled platelet scanning is an effective way to identify those transplants that are at risk for acute loss. Two hundred prospective /sup 111/In scans were obtained (100 on allografts with normal function and 100 with transplant dysfunction of all causes). /sup 111/In scans in patients with dose-dependent CSA nephrotoxicity (N = 58) and biopsy proved acute rejection (N = 22) were negative. Grossly abnormal scans (three to eight times greater than hepatic uptake) were noted in nine recipients identified as having a hemolytic uremic-like syndrome associated with CSA use. Accelerated allograft functional loss was irreversible in six patients despite stopping CSA, systemic anticoagulation, increased steroids and antilymphocyte globulin, and infusion of fresh-frozen plasma. Three patients with grossly positive /sup 111/In scans and clinical and laboratory parameters consistent with this syndrome were treated with cessation of CSA and intra-arterial infusion of streptokinase into the renal allograft followed by systemic heparinization. Normal transplant function was regained and continues at 1, 7, and 8 months after transplant. /sup 111/In-labeled platelet scanning can noninvasively identify this syndrome of CSA-associated arteriopathy and allow for early therapy to reverse it. Intrarenal arterial streptokinase therapy is a successful way to treat acute CSA-associated arteriopathy.

  8. Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma

    SciTech Connect

    Abdel-Nabi, H.H.; Chan, H.W.; Doerr, R.J. )

    1990-12-01

    Indium-111- ({sup 111}In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of {sup 111}In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with {sup 111}In-ZCE 025 (n = 37) or {sup 111}In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of {sup 111}In-labeled MAb scan interpretation.

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

    PubMed

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

    2012-09-10

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

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

    SciTech Connect

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

    1988-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  12. 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.

  13. DOTA alpha-melanocyte-stimulating hormone analogues for imaging metastatic melanoma lesions.

    PubMed

    Froidevaux, Sylvie; Calame-Christe, Martine; Sumanovski, Lazar; Tanner, Heidi; Eberle, Alex N

    2003-06-01

    Scintigraphic imaging of metastatic melanoma lesions requires highly tumor-specific radiopharmaceuticals. Because both melanotic and amelanotic melanomas overexpress melanocortin-1 receptors (MC1R), radiolabeled analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) are potential candidates for melanoma diagnosis. Here, we report the in vivo performance of a newly designed octapeptide analogue, [betaAla(3), Nle(4), Asp(5), D-Phe(7), Lys(10)]-alpha-MSH(3-10) (MSH(OCT)), which was conjugated through its N-terminal amino group to the metal chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to enable incorporation of radiometals (e.g., indium-111) into the peptide. DOTA-MSH(OCT) displayed high in vitro MC1R affinity (IC(50) 9.21 nM). In vivo [(111)In]DOTA-MSH(OCT) exhibited a favorable biodistribution profile after injection in B16-F1 tumorbearing mice. The radiopeptide was rapidly cleared from blood through the kidneys and, most importantly, accumulated preferentially in the melanoma lesions. Lung and liver melanoma metastases could be clearly imaged on tissue section autoradiographs 4 h after injection of [(111)In]DOTA-MSH(OCT). A comparative study of [(111)In]DOTA-MSH(OCT) with [(111)In]DOTA-[Nle(4), D-Phe(7)]-alpha-MSH ([(111)In]-DOTA-NDP-MSH) demonstrated the superiority of the DOTA-MSH(OCT) peptide, particularly for the amount of radioactivity taken up by nonmalignant organs, including bone, the most radiosensitive tissue. These results demonstrate that [(111)In]DOTA-MSH(OCT) is a promising melanoma imaging agent.

  14. 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.

  15. 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

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

    PubMed

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

    2015-01-01

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

  17. 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.

  18. 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.

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

    SciTech Connect

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

    1986-10-01

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

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

    PubMed

    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 (125)I and (111)In. (111)In-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 (111)In-/(125)I-HP2 to ZHER2:342-SR-HP1 pre-treated cells was demonstrated. (111)In-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 (111)In-ZHER2:342-SR-HP1. The complementary PNA probe (111)In/(125)I-HP2 accumulated in SKOV-3 xenografts when ZHER2:342-SR-HP1 was injected 4 h earlier. The tumor accumulation of (111)In/(125)I-HP2 was negligible without ZHER2:342-SR-HP1 pre-injection. The uptake of (111)In-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.

  1. 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

  2. Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

    PubMed

    Schillaci, Orazio; DeNardo, Gerald L; DeNardo, Sally J; Goldstein, Desiree S; Kroger, Linda A; O'Donnell, Robert T; Lamborn, Kathleen R

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.

  3. Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction

    SciTech Connect

    Jain, D.; Crawley, J.C.; Lahiri, A.; Raftery, E.B. )

    1990-02-01

    The results of indium-111 ({sup 111}In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received {sup 111}In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal {sup 111}In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when {sup 111}In-antimyosin is injected six days postinfarction.

  4. Vacuum synthesis of magnetic aluminum phthalocyanine on Au(111).

    PubMed

    Hong, I-Po; Li, Na; Zhang, Ya-Jie; Wang, Hao; Song, Huan-Jun; Bai, Mei-Lin; Zhou, Xiong; Li, Jian-Long; Gu, Gao-Chen; Zhang, Xue; Chen, Min; Gottfried, J Michael; Wang, Dong; Lü, Jing-Tao; Peng, Lian-Mao; Hou, Shi-Min; Berndt, Richard; Wu, Kai; Wang, Yong-Feng

    2016-08-16

    Air-unstable magnetic aluminum phthalocyanine (AlPc) molecules are prepared by an on-surface metalation reaction of phthalocyanine with aluminum (Al) atoms on Au(111) in ultrahigh vacuum. Experiments and density functional theory calculations show that an unpaired spin is located on the conjugated isoindole lobes of the molecule rather than at the Al position. PMID:27406881

  5. 99mTc-human immunoglobulin (HIG)--first results of a new agent for the localization of infection and inflammation.

    PubMed

    Buscombe, J R; Lui, D; Ensing, G; de Jong, R; Ell, P J

    1990-01-01

    Technetium (99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely 111In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for 99mTc-HIG when 111In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both 99mTc-HIG and 111In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the 99mTc-HIG scan, and one case of pyrexia of unknown origin when the 99mTc-HIG was false-negative and the 111In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for 99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.

  6. Indium-111-chloride and three-phase bone scintigraphy: A comparison for imaging experimental osteomyelitis

    SciTech Connect

    Hoskinson, J.J.; Daniel, G.B.; Patton, C.S. )

    1991-01-01

    To investigate the utility of indium-111-chloride ({sup 111}In-Cl) imaging in detecting osteomyelitis complicating surgical or fracture sites, the proximal tibia of 11 dogs were experimentally infected with Staphylococcus aureus after creation of a cortical defect. The contralateral limb served as a sham-operated control. Animals were serially imaged by radiography, three-phase technetium-99m-methylene diphosphonate (99mTc-MDP) scintigraphy, and {sup 111}In-Cl scintigraphy. There was a significant difference between infected (1.93) and noninfected (1.32) limb's tibia/femur count density ratios on 24-hr (p = 0.0001) and 72-hr (p = 0.0001) {sup 111}In-Cl images. A smaller difference was found for 99mTc-MDP bone-phase tibia/femur ratios (p = 0.0199). Using receiver operator characteristic analysis of tibia/femur ratios, a sensitivity of 61%, specificity of 88%, and positive (75%) and negative (79%) predictive values were determined for the 24-hr {sup 111}In-Cl images. Indium-111-chloride was superior to 99mTc-MDP in differentiating infected and noninfected operative sites.

  7. In vivo integrity of polymer-coated gold nanoparticles.

    PubMed

    Kreyling, Wolfgang G; Abdelmonem, Abuelmagd M; Ali, Zulqurnain; Alves, Frauke; Geiser, Marianne; Haberl, Nadine; Hartmann, Raimo; Hirn, Stephanie; de Aberasturi, Dorleta Jimenez; Kantner, Karsten; Khadem-Saba, Gülnaz; Montenegro, Jose-Maria; Rejman, Joanna; Rojo, Teofilo; de Larramendi, Idoia Ruiz; Ufartes, Roser; Wenk, Alexander; Parak, Wolfgang J

    2015-07-01

    Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

  8. A DOTA-peptide conjugate by copper-free click chemistry.

    PubMed

    Martin, Molly E; Parameswarappa, Sharavathi G; O'Dorisio, M Sue; Pigge, F Christopher; Schultz, Michael K

    2010-08-15

    Attachment of DOTA to a novel monofluoro-cyclooctyne facilitates bioconjugation to an azide-modified peptide via Cu-free click chemistry. The resulting conjugate was radiolabeled with (111)In to afford a potential targeted molecular imaging agent with high specific activity and an excellent radiochemical purity.

  9. Clinical evaluation of radio-labelled bleomycin for tumor detection.

    PubMed

    Rasker, J J; Beekhuis, H; van de Poll, M A; Versluis, A; Jurjens, H; Woldring, M G

    1978-12-01

    Investigations with bleomycin labelled with radionuclides other than 57Co in patients with cancer and in tumor-bearing animals are described. In patients 57Co-bleo appears to be a better tumor-seeking radiopharmaceutical than 111In-bleo, 99mTc-bleo or 197Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of 57Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram. Results with 111In-bleo labelled in acidic solution are not essentially different from those with 111In-bleo labelled in neutral solution. Results of 197Hg-bleo are almost identical with those of 197HgCl2 regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of 197Hg to bleomycin is not stable in vivo. The superiority of 57Co-bleo over 99mTc-bleo, 197Hg-bleo and also over 67Cu-bleo is confirmed by experiments on tumor bearing animals. We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with 111In, 99mTc, 197Hg or 67Cu seems to be very limited.

  10. 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.

  11. In vivo kinetics of radiolabeled monoclonal anti-CEA antibodies in animal models

    SciTech Connect

    Hagan, P.L.; Halpern, S.E.; Chen, A.; Krishnan, L.; Frincke, J.; Bartholomew, R.M.; David, G.S.; Carlo, D.

    1985-12-01

    Studies were performed to determine the effect of the radiolabel and circulating carcinoembryonic antigen (CEA) on the pharmacodynamics of monoclonal anti-CEA antibodies (MoAbs). The studies were performed in normal BALB/c mice and in nude mice bearing human colon tumors. Three different tumors were used, each of which produced CEA levels characteristic of that particular tumor's secretory rate. The CEJ-326 MoAb labeled with either 111In or 125I was used in all studies. Circulating CEA induced the removal of 125I and 111In MoAbs from the vascular compartment. Liver concentrations of 111In increased and 125I levels decreased as the CEA secretory rate of the tumor rose. This indicates that circulating CEA complexes form in the vascular compartment which, in an animal model, are removed by the liver and spleen. This results in decreased tumor uptake of the labeled MoAb. The iodinated MoAb complexes are dehalogenated while the 111In is retained by the liver. This dehalogenation may account for the relatively low liver activity observed in radioimmunoimaging with intact radioiodinated anti-CEA MoAbs, provided the CEA complexes are similarly removed from the vascular compartment by the human liver.

  12. Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study

    SciTech Connect

    Doerr, R.J.; Abdel-Nabi, H.; Krag, D.; Mitchell, E. )

    1991-08-01

    Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.

  13. 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.

  14. Radioimmunoimaging of lung vessels: An approach using indium-111-labeled monoclonal antibody to angiotensin-converting enzyme

    SciTech Connect

    Danilov, S.M.; Martynov, A.V.; Klibanov, A.L.; Slinkin, M.A.; Sakharov, I.Yu.; Malov, A.G.; Sergienko, V.B.; Vedernikov, A.Yu.; Muzykantov, V.R.; Torchilin, V.P.

    1989-10-01

    A murine monoclonal antibody against human angiotensin-converting enzyme was radiolabeled with {sup 111}In via diethylenetriaminepentaacetic acid without substantial loss of antigen-binding capacity. This monoclonal antibody designated 9B9 cross-reacted with rat and monkey angiotensin-converting enzyme. Indium-111-labeled 9B9 selectively accumulated 10-20 times greater in the lung than in blood or other organs following intravenous administration in rats. Kinetics of lung accumulation and blood clearance were studied for {sup 111}In-9B9-antibody and compared to that of {sup 125}I-labeled 9B9 in rat. Highly specific accumulation of {sup 111}In-9B9-antibody in the lung of Macaca Rhesus monkeys after intravenous injection was monitored by gamma-imaging. Images of {sup 111}In-labeled antibody 9B9 biodistribution in monkey lung noticeably differ from the images of biodistribution of {sup 99m}Tc-labeled albumin microspheres. This difference may provide information concerning the state of the endothelium of lung capillaries, which is different from the blood flow characteristics determined with routine microsphere technique.

  15. In vivo integrity of polymer-coated gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Kreyling, Wolfgang G.; Abdelmonem, Abuelmagd M.; Ali, Zulqurnain; Alves, Frauke; Geiser, Marianne; Haberl, Nadine; Hartmann, Raimo; Hirn, Stephanie; de Aberasturi, Dorleta Jimenez; Kantner, Karsten; Khadem-Saba, Gülnaz; Montenegro, Jose-Maria; Rejman, Joanna; Rojo, Teofilo; de Larramendi, Idoia Ruiz; Ufartes, Roser; Wenk, Alexander; Parak, Wolfgang J.

    2015-07-01

    Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles (198Au) and engineered an 111In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for 198Au and 111In showed partial removal of the polymer shell in vivo. While 198Au accumulates mostly in the liver, part of the 111In shows a non-particulate biodistribution similar to intravenous injection of chelated 111In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

  16. Schools Reaching Out and Success for All Children: Two Case Studies.

    ERIC Educational Resources Information Center

    Swap, Susan McAllister

    This research report evaluates a 2-year effort to achieve home-school partnerships and success for all children at two urban schools: P.S. 111 in New York City and the Ellis School in Boston. As conceptualized by the Institute for Responsive Education staff, the process of achieving success for all children required the transformation of school…

  17. Role of phosphate-containing compounds in the transfer of indium-111 and gallium-67 from transferrin to ferritin.

    PubMed

    Weiner, R E

    1989-01-01

    Physiologic concentrations of ATP stimulate the translocation of gallium-67 (67Ga) from human transferrin (TF) to horse ferritin (HoFE). The mechanism of this translocation was examined. One millimolar ATP did not speed the binding of 67Ga or indium-111 (111In) to HoFE. ATP and pyrophosphate (PPi) at 1 mM, did not form high affinity complexes with 67Ga or 111In. ATP and PPi interacted directly with the [67Ga]TF complex and could within minutes increase the amount of nonprotein-bound 67Ga. Serum HCO3- concentration, 30 mM, prevented the ATP-induced dissociation of 67Ga from TF, whereas intracellular concentrations (0.4 and 5 mM) did not. Using a dialysis technique, ATP also stimulated the translocation of 111In from TF to HoFE; however, this process was much slower than with 67Ga. ATP caused an increase in the nonprotein-bound 111In compared to the control. These results suggest the formation of nonprotein-bound nuclide by these phosphate-containing compounds in a kinetically labile form is important to the translocation mechanism. PMID:2536083

  18. 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…

  19. 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.

  20. 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)

  1. 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

  2. Hepatocyte-specific distribution of catalase and its inhibitory effect on hepatic ischemia/reperfusion injury in mice.

    PubMed

    Yabe, Y; Koyama, Y; Nishikawa, M; Takakura, Y; Hashida, M

    1999-04-01

    To explore the possibility of using catalase for the treatment of reactive oxygen species (ROS)-mediated injuries, the pharmacokinetics of bovine liver catalase (CAT) labeled with 111In was investigated in mice. At a dose of 0.1 mg/kg, more than 70% of 111In-CAT was recovered in the liver within 10 min after intravenous injection. In addition, 111In-CAT was predominantly recovered from the parenchymal cells (PC) in the liver. Increasing the dose retarded the hepatic uptake of 111In-CAT, suggesting saturation of the uptake process. This cell-specific uptake could not be inhibited by coadministration of various compounds which are known to be taken up by liver PC, indicating that the uptake mechanism of CAT by PC is very specific to this compound. The preventive effect of CAT on a hepatic ischemia/reperfusion injury was examined in mice by measuring the GOT and GPT levels in plasma. A bolus injection of CAT at 5 min prior to the reperfusion attenuated the increase in the levels of these indicators in a dose-dependent manner. These results suggest that catalase can be used for various hepatic injuries caused by ROS. PMID:10230805

  3. In vivo integrity of polymer-coated gold nanoparticles.

    PubMed

    Kreyling, Wolfgang G; Abdelmonem, Abuelmagd M; Ali, Zulqurnain; Alves, Frauke; Geiser, Marianne; Haberl, Nadine; Hartmann, Raimo; Hirn, Stephanie; de Aberasturi, Dorleta Jimenez; Kantner, Karsten; Khadem-Saba, Gülnaz; Montenegro, Jose-Maria; Rejman, Joanna; Rojo, Teofilo; de Larramendi, Idoia Ruiz; Ufartes, Roser; Wenk, Alexander; Parak, Wolfgang J

    2015-07-01

    Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo. PMID:26076469

  4. Chelate conjugates of monoclonal antibodies for imaging lymphoid structures in the mouse

    SciTech Connect

    Goodwin, D.A.; Meares, C.F.; McCall, M.J.; Haseman, M.K.; McTigue, M.; Diamanti, C.I.; Chaovapong, W.

    1985-05-01

    Radiolabeling of a mouse monoclonal antibody (MoAb) specific for the mouse histocompatibility alloantigen lA/sup k/ expressed by the B lymphocytes of BALB/k and C3H mice but not BALB/c mice was performed by mixing the chelate-labeled anti (..cap alpha..) lA/sup k/ MoAb with purified, no-carrier-added /sup 111/In citrate. The organ, spleen, and lymph node distribution of intravenously and subcutaneously administered /sup 111/In..cap alpha..lA/sup k/ MoAb was compared in mice, two lA/sup k/ positive and one lA/sup k/ negative strains, and to /sup 125/l..cap alpha..lA/sup k/ MoAb in one 1A/sup K/ positive strain. The /sup 111/In..cap alpha.. 1A/sup K/ MoAb was more stable in vivo compared to /sup 125/I..cap alpha.. 1A/sup K/ MoAb as shown by a much slower excretion and a higher absolute uptake in lymph nodes and spleen. Potential clinical applications of /sup 111/In..cap alpha.. lymphocyte MoAb include localization of normal lymph nodes and T and B cell leukemias and lymphomas, as well as detecting lymphatic metastases of other cancers.

  5. 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.

  6. 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.

  7. 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…

  8. Loss of /sup 51/chromium, lactate dehydrogenase, and /sup 111/indium as indicators of endothelial cell injury

    SciTech Connect

    Chopra, J.; Joist, J.H.; Webster, R.O.

    1987-11-01

    Injury to endothelial cells appears to be an important initial event in the pathogenesis of many diseases such as acute lung injury, venous and arterial thromboembolism, and atherosclerosis. Different methods for detecting damage to cultured endothelial cells have been described. However, their relative sensitivity as markers of endothelial cell damage has not been adequately determined. We compared the loss of /sup 51/Chromium (/sup 51/Cr), the cytoplasmic enzyme lactate dehydrogenase (LDH), and /sup 111/Indium (/sup 111/In) from endothelial cells upon exposure to several injurious agents. Cultured bovine pulmonary artery endothelial cells in confluent monolayers were labeled with /sup 51/Cr or /sup 111/Inoxine and exposed to increasing concentrations of the nonionic detergent, Triton X-100 (0.2 to 1%), hydrogen peroxide (1 to 500 microM), or neutrophils stimulated with phorbol myristate acetate. With all forms of injury, loss of /sup 51/Cr occurred earlier and to a greater extent than LDH loss which in turn was greater than loss of /sup 111/In. Substantial loss of /sup 51/Cr was observed in the absence of appreciable ultrastructural damage to endothelial cell external membranes. The findings may reflect the relative ease with which small molecules such as adenine nucleotides (/sup 51/Cr-labeled) escape whereas larger molecules such as LDH and proteins binding /sup 111/In are retained intracellularly. Thus, /sup 51/Cr loss appears to be a more sensitive indicator of sublytic endothelial cell injury than either /sup 111/In or LDH release.

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

    PubMed

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

    2016-08-10

    Recently, we developed 2nd generation backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates which contain enzymatically cleavable sequences (GFLG) in both polymeric backbone and side-chains. This design allows using polymeric carriers with molecular weights above renal threshold without impairing their biocompatibility, thereby leading to significant improvement in therapeutic efficacy. For example, 2nd generation HPMA copolymer-epirubicin (EPI) conjugates (2P-EPI) demonstrated complete tumor regression in the treatment of mice bearing ovarian carcinoma. To obtain a better understanding of the in vivo fate of this system, we developed a dual-labeling strategy to simultaneously investigate the pharmacokinetics and biodistribution of the polymer carrier and drug EPI. First, we synthesized two different types of dual-radiolabeled conjugates, including 1) (111)In-2P-EPI-(125)I (polymeric carrier 2P was radiolabeled with (111)In and drug EPI with (125)I), and 2) (125)I-2P-EPI-(111)In (polymeric carrier 2P was radiolabeled with (125)I and drug EPI with (111)In). Then, we compared the pharmacokinetics and biodistribution of these two dual-labeled conjugates in female nude mice bearing A2780 human ovarian carcinoma. There was no significant difference in the blood circulation between polymeric carrier and payload; the carriers ((111)In-2P and (125)I-2P) showed similar retention of radioactivity in both tumor and major organs except kidney. However, compared to (111)In-labeled payload EPI, (125)I-labeled EPI showed lower radioactivity in normal organs and tumor at 48h and 144h after intravenous administration of conjugates. This may be due to different drug release rates resulting from steric hindrance to the formation of enzyme-substrate complex as indicated by cleavage experiments with lysosomal enzymes (Tritosomes). A slower release rate of EPI(DTPA)(111)In than EPI(Tyr)(125)I was observed. It may be also due to in vivo catabolism and

  10. Immunospecific saturable clearance mechanisms for indium-111-labeled anti-melanoma monoclonal antibody 96. 5 in humans

    SciTech Connect

    Murray, J.L.; Lamki, L.M.; Shanken, L.J.; Blake, M.E.; Plager, C.E.; Benjamin, R.S.; Schweighardt, S.; Unger, M.W.; Rosenblum, M.G.

    1988-08-01

    Liver uptake of 111In-labeled monoclonal antibodies (MoAb) remains a significant problem in radioimaging studies to date. To determine if the observed liver uptake of an 111In-labeled anti-melanoma antibody 96.5 (111In-96.5) was dependent on the presence of hepatic antigen or on recognition of circulating murine antibody, escalating doses of an unlabeled nonimmunoreactive MoAb (NIR-MoAb) were administered to 18 patients with metastatic malignant melanoma either 1 or 24 h prior to an infusion of 1 mg of 111In-96.5. The number of metastases imaged, pharmacokinetics, and the ratio of radioactivity (expressed as average counts/pixel) in liver (L), spleen (S), bone (B), and kidney (K) compared to blood pool (heart = H) were examined. Results were prospectively compared with data from six patients who received immunoreactive unlabeled 96.5 prior to 111In-96.5. Increasing dose or changes in the preinfusion time of NIR-MoAb had no significant effect on the biodistribution of 111In-96.5. In contrast, patients who received unlabeled, immunoreactive 96.5 prior to 111In-96.5 infusion demonstrated a significant drop (P less than 0.001) in the liver/heart ratio of radioactivity (2.81 +/- 0.35 (SEM)) compared to patients receiving the identical dose of NIR-MoAb (10.35 +/- 1.33). Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t1/2 both decreased when 96.5 was administered compared to NIR-MoAb. In addition, a 4-fold increase in concentration X time was obtained after 96.5 antibody was administered compared to NIR-MoAb. More metastases were imaged in patients receiving preinfusions of 96.5 (23 of 28) than in patients receiving NIR-MoAb (10 of 18; P less than 0.05).

  11. 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

  12. Indium-111-Photofrin-II scintillation scan

    SciTech Connect

    Origitano, T.C.; Karesh, S.M.; Reichman, O.H.; Henkin, R.E.; Caron, M.J.

    1989-04-01

    Photodynamic therapy is under intense investigation as an adjuvant treatment for malignant glial tumors of the central nervous system. Photofrin-II (HpD-II) is currently the most actively investigated photosensitizing agent. A crucial issue regarding the safe and efficacious usage of HpD-II-based photodynamic therapy is the individual in vivo kinetics of tumor uptake and retention, compared with normal brain clearance. The optimal time for photoactivation of sensitized tumor must be known to ensure a high target-to-nontarget ratio, resulting in the maximal tumor destruction while preserving normal brain. Our laboratory developed a radionuclide scan based on 111indium (111In)-labeled HpD-II to evaluate HpD-II localization and clearance noninvasively within a canine model of intracerebral gliosarcoma. Synthesis of the 111In-HpD-II complex in greater than 90% yield is achieved by a simple, rapid labeling method. Radiochemical purity and stability were verified by high-performance liquid chromatography. Using the canine model of intracerebral gliosarcoma, we followed the uptake of 111In-HpD-II in tumors with serial scintillation scanning. Localization of the tumor by 111In-HpD-II has been verified by contrast-enhanced computed tomographic scan followed by gross and histological examination of the enhancing brain region. Total body biodistribution of 111In-HpD-II at various times after injection has been evaluated. The ratio of uptake in tumor compared with surrounding brain peaked at 72 hours after injection. The knowledge of regional distribution and concentration of a photosensitizing agent within a tumor mass and surrounding brain allows for the most efficacious timing and localization of a photoactivating source.

  13. 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

  14. 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

  15. Respiratory clearance of aerosolized radioactive solutes of varying molecular weight

    SciTech Connect

    Huchon, G.J.; Montgomery, A.B.; Lipavsky, A.; Hoeffel, J.M.; Murray, J.F.

    1987-05-01

    To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium /sup 99m/Tc pertechnetate (TcO4), /sup 99m/Tc glucoheptonate ((/sup 99m/Tc)GH), 51Cr-ethylenedinitrotetraacetate ((51Cr)EDTA), /sup 99m/Tc diethylenetriaminepentaacetate ((99mTc) DTPA), /sup 111/In diethylenetriaminepentaacetate ((/sup 111/In)DTPA), /sup 67/Ga desferoxaminemesylate ((/sup 67/Ga)DFOM), /sup 99m/Tc dextran ((/sup 99m/Tc)DX) and /sup 111/In transferrin ((/sup 111/In)TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), (/sup 99m/Tc)GH (1.50 +/- 0.37%/min), (/sup 51/Cr)EDTA (2.38 +/- 1.02%/min), (/sup 99m/Tc)DTPA (3.51 +/- 0.40%/min), (/sup 111/In)DTPA (2.35 +/- 0.42%/min), (/sup 67/Ga) DFOM (1.99 +/- 0.49%/min) and (/sup 99m/Tc)DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.

  16. Improved biodistribution and radioimmunoimaging with poly(ethylene glycol)-DOTA-conjugated anti-CEA diabody.

    PubMed

    Li, Lin; Yazaki, Paul J; Anderson, Anne-Line; Crow, Desiree; Colcher, David; Wu, Anna M; Williams, Lawrence E; Wong, Jeffrey Y C; Raubitschek, Andrew; Shively, John E

    2006-01-01

    Diabodies are single chain antibody fragments (scFvs) that spontaneously form bivalent dimers of molecular size 50-55000. Radiolabeled diabodies are almost ideal tumor targeting agents due to their high avidity (bivalent) binding to tumor antigens and small size (50-55000) that leads to improved tumor-to-blood ratio compared to intact antibodies (150000). However, due to their high retention and metabolism in the kidney, radioiodine is the current radiolabel of choice for diabodies since radioiodine is rapidly excreted from the kidney once metabolized. We have previously shown that 111In-DOTA-diabody gives higher tumor uptake in nude mouse xenografts than 125I-diabody, but has extremely high kidney retention since its 111In-labeled metabolites are retained by and only slowly excreted from the kidney. When a diabody is conjugated to a bifunctional PEG-3400 derivative followed by reaction with cysteinyl-DOTA, the resulting product has an apparent molecular size of 75000 and a Stokes radius of 35 angstroms on size exclusion chromatography, compared to a Stokes radius of 25 angstroms for intact diabody. When radiolabeled, the conjugate gives high yields of 111In-labeled product, retains high immunoreactivity, and gives improved biodistributions (30-40%ID/g, 12-48 h) compared to 111In-DOTA-diabody (12-13%ID/g, 6-12 h). We show that the improved biodistribution is due to an increase in Stokes radius caused by the linear PEG-3400 since conjugation of diabody with multiple (PEG)12 linkers followed by reaction with cysteinyl-DOTA does not reduce kidney accumulation. We also show that 111In-cysteinyl-DOTA-PEG3400-diabody gives excellent tumor images in the nude mouse xenograft model and that 125I-PEG3400-diabody gives equivalent images to 125I-minibody (molecular size, 80000), but improved tumor-to-liver ratios, suggesting that this imaging agent can be used to image liver metastases.

  17. Targeting HER2

    PubMed Central

    Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W

    2010-01-01

    The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama. PMID:20716957

  18. Evaluation of primary lung cancer with indium 111 anti-carcinoembryonic antigen (type ZCE-025) monoclonal antibody scintigraphy

    SciTech Connect

    Krishnamurthy, S.; Morris, J.F.; Antonovic, R.; Ahmed, A.; Galey, W.T.; Duncan, C.; Krishnamurthy, G.T. )

    1990-02-01

    A study was undertaken to test whether indium 111 (111In)-labeled anti-carcinoembryonic antigen (CEA) (type ZCE 025) monoclonal intact antibody (MoAb) would concentrate in primary lung cancer enabling its detection and localization by scintigraphy. The scintigraphic results were correlated with chest radiograph, computed tomograph (CT), bronchoscopy, surgical resection, and tumor CEA analysis. Twenty adult male patients with clinical suspicion of primary lung cancer were studied. Each subject was infused with 4 to 5 mCi of 111In anti-CEA ZCE 025 MoAb, and planar and tomographic scintiphotos were obtained on days 3 and 6 or 7 postinfusion. The scintigraphy was true-positive in 12 of 16 patients with primary lung cancer, eight of nine patients with squamous cell carcinoma, and four of seven with adenocarcinoma; it was true-negative in three of four patients with benign lung disease with an overall accuracy of 75%. In seven patients with confirmed primary lung cancer, but with negative bronchoscopic findings, the scintigraphy was true-positive in four. In 11 patients with definitely positive or suspicious malignancy by bronchoscopy the monoclonal scintigraphy was positive in eight. In true-positive cases, the location and size of the lesion by 111In anti-CEA ZCE 025 MoAb imaging correlated well with CT findings and also tumor mass at surgery. Only one of 12 tumors stained positive for CEA had serum CEA levels greater than 10 ng/ml, indicating nonleakage of the tumor antigen into general circulation in early lung cancer. It is concluded that 111In anti-CEA ZCE 025 MoAb planar and tomographic imaging shows potential to serve as a noninvasive diagnostic test in the evaluation of primary lung cancer. The lung lesion is likely to be malignant if it concentrates 111In anti-CEA ZCE 025 MoAb and benign if it does not.

  19. Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor-imaging studies

    SciTech Connect

    Brechbiel, M.W.; Gansow, O.A.; Atcher, R.W.; Schlom, J.; Esteban, J.; Simpson, D.E.; Colcher, D.

    1986-07-30

    To investigate the /sup 111/In labeling of tumor-localizing monoclonal antibodies (MoAb), the chelate 1-(p-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid (p-SCN-Bz-DPTA) (1) and its EDTA analogue (2) have been synthesized. By the use of a MoAb (B72.3) specific for a high molecular weight antigen (TAG-72) on cells of a colorectal carcinoma grown in nude mice, optimal chemical conditions for MoAb conjugation of those ligands and of the dicyclic and isobutylcarboxy carbonic anhydrides of DTPA and subsequent /sup 111/In labeling were determined. All conjugates were shown by a competitive binding assay to retain their specificity and activity in vitro when less than one ligand is protein coupled both prior to and after /sup 111/In labeling. Chemical methods for purification of the MoAb were systematically investigated by injection of purified immunoprotein into athymic mice bearing LS-174T tumors that express the TAG-72 antigen. Tissue distribution studies revealed that simple addition of EDTA to labeled immunoglobulins was ineffective at complexing indium not linked to protein by chelates. Similarly, gel chromatography (Sephadex G-50) was not sufficient; rather, size exclusion HPLC had to be employed to remove unreacted /sup 111/In and aggregated antibody. To compare the relative utility of the four chelates for /sup 111/In diagnostic radioimmunoimaging, scintigraphic images of tumor-bearing mice were obtained and evaluated along with tissue distributions. Results showed that clear images of these solid tissue tumors free of extraneous radiation could be obtained only by using p-SCN-Bz-DTPA purified by HPLC. Methods developed are now being employed in clinical trials for diagnosis of human colorectal cancer. 71 references, 5 figures, 1 table.

  20. Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018

    SciTech Connect

    Murray, J.L.; Rosenblum, M.G.; Lamki, L.; Glenn, H.J.; Krizan, Z.; Hersh, E.M.; Plager, C.E.; Bartholomew, R.M.; Unger, M.W.; Carlo, D.J.

    1987-01-01

    Radioimmunolocalization of an /sup 111/In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single. i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi /sup 111/In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel, testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p less than 0.005). A significant correlation was observed between tumor uptake of /sup 111/In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T1/2 of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of /sup 111/In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with /sup 111/In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

  1. Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk

    SciTech Connect

    Johnson, L.L.; Seldin, D.W.; Keller, A.M.; Wall, R.M.; Bhatia, K.; Bingham, C.O. III; Tresgallo, M.E. )

    1990-01-01

    Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.

  2. 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

  3. Technique of leukocyte harvesting and labeling: problems and perspectives

    SciTech Connect

    McAfee, J.G.; Subramanian, G.; Gagne, G.

    1984-04-01

    Mixed leukocyte suspensions obtained after gravity sedimentation of red cells and labeled with /sup 111/In lipophilic chelates are now widely used clinically for abscess localization at many medical centers. So far, labeling with /sup 111/In-oxine or tropolone has been more successful than any /sup 99/mTc method. More sophisticated approaches are available for isolation and labeling of specific leukocyte cell types, to study their migration in vivo. The most significant advances in cell harvesting include newer density gradients for isopyknic centrifugation, centrifugal elutriation, and flow cytometry. Unlike current radioactive agents which label many cell types indiscriminately, more selective ligands are being developed which bind to specific cell surface receptors. These will label certain leukocyte populations or subtypes while not reacting with others, thereby avoiding laborious separation techniques. Monoclonal antibodies against leukocyte cell-surface antigens appear particularly promising as agents for selective cell labeling.

  4. Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments

    SciTech Connect

    Rosebrough, S.F.; Grossman, Z.D.; McAfee, J.G.; Kudryk, B.J.; Subramanian, G.; Ritter-Hrncirik, C.A.; Witanowski, L.S.; Tillapaugh-Fay, G.; Urrutia, E.; Zapf-Longo, C.

    1988-07-01

    We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with /sup 131/I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with /sup 131/I-labeled F(ab')2 and Fab and /sup 111/In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with /sup 111/In and its better physical characteristics for imaging, compared to /sup 131/I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging.

  5. 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)

  6. Indium-111-labeled leukocyte scintigraphy in hemodialysis access-site infection

    SciTech Connect

    Palestro, C.J.; Vega, A.; Kim, C.K.; Vallabhajosula, S.; Goldsmith, S.J. )

    1990-03-01

    Bacterial sepsis, a significant complication of chronic hemodialysis, is generally the result of infection at the vascular access site. We retrospectively reviewed the utility of indium-111-(111In) labeled autologous leukocyte scintigraphy in 26 patients (30 scans) with synthetic vascular grafts, on chronic hemodialysis, in whom hemodialysis access site infection was a diagnostic consideration. Leukocyte scintigraphy correctly identified all fifteen access-site infections; there was one false-positive study, for an overall sensitivity and specificity of 100% and 93%, respectively. Of particular significance is the fact that in nine (60%) of the fifteen access-site infections, physical examination was normal. Our data indicate that 111In-labeled leukocyte scintigraphy is a useful procedure for the diagnosis of hemodialysis access-site infection, and it is especially valuable when physical examination of the access site is normal.

  7. No difference in sensitivity for occult infection between tropolone- and oxine-labeled indium-111 leukocytes

    SciTech Connect

    Datz, F.L.; Bedont, R.A.; Baker, W.J.; Alazraki, N.P.; Taylor, A. Jr.

    1985-05-01

    There is considerable disagreement as to whether oxine or tropolone is the best labeling agent for indium leukocytes. The authors have previously looked at the sensitivity of oxine-labeled /sup 111/In leukocyte scans for occult infections and now present a similar group of patients imaged with tropolone-labeled /sup 111/In leukocytes. Thirty-four patients (38 studies) with possible occult infection were prospectively studied. Patients were imaged 1-4 hr after injection and again at 24 hr postinjection. The differences in sensitivity between oxine and tropolone when imaged early and at 24 hr were not statistically significant. They conclude that there is not significant difference in the ability to detect infection between oxine- and tropolone-labeled leukocytes, both early at 1-4 hr, and on delayed imaging 24 hr after injection.

  8. Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: The effect of antibiotic treatment

    SciTech Connect

    Chung, C.J.; Hicklin, O.A.; Payan, J.M.; Gordon, L. )

    1991-01-01

    To determine the sensitivity and specificity of the indium-111-({sup 111}In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed. Of 41 consecutive {sup 111}In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics. The average duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans for graft infection were found. By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%.

  9. Magnetic Properties of Grain Boundaries of Nanocrystalline Ni and of Ni Precipitates in Nanocrystalline NiCu Alloys

    NASA Astrophysics Data System (ADS)

    Wolf, H.; Guan, Z.; Li, X.; Wichert, Th.

    2001-11-01

    Perturbed γγ-angular correlation spectroscopy (PAC) was used to investigate nanocrystalline Ni and NiCu alloys, which are prepared by pulsed electrodeposition (PED). Using diffusion for doping nanocrystalline Ni with 111In four different ordered grain boundary structures are observed, which are characterized by unique electric field gradients. The incorporation of 111In on substitutional bulk sites of Ni is caused by moving grain boundaries below 1000 K and by volume diffusion above 1000 K. The nanocrystalline NiCu alloys prepared by PED are microscopically inhomogeneous as observed by PAC. In contrast, this inhomogeneity cannot be detected by X-ray diffraction. The influence of the temperature of the electrolyte, the current density during deposition, and the optional addition of saccharin to the electrolyte on the homogeneity of nanocrystalline NiCu alloys was investigated.

  10. Uptake of indium-111-labeled monoclonal antibody ZME-018 as a function of tumor size in a patient with melanoma

    SciTech Connect

    Macey, D.J.; Denardo, S.J.; Denardo, G.L.; Goodnight, J.K.; Unger, M.W.

    1988-01-01

    The accumulation of an Indium-111-labeled monoclonal antibody (MoAb), ZME-018, in melanoma tumors in a patient was determined by sequential, quantitative gamma camera imaging. The amount and concentration of In-111 in each tumor changed in a characteristic pattern with time, reaching a peak at day 3 followed by a steady clearance. The concentration of In-111 in the tumor and the ratios of tumor to whole-body or blood decreased as the size of the tumor increased. These results were interpreted to indicate that the fraction of active, perfused tumor decreased as the melanoma lesions increased in size. The maximum number of MoAb molecules bound per melanoma cell was calculated to be abut 35,000. The implications of these observations for radioimmunoimaging and therapy are significant.

  11. SPECT assay of radiolabeled monoclonal antibodies. Comprehensive progress report, September 1989--February 1992

    SciTech Connect

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  12. SPECT assay of radiolabeled monoclonal antibodies

    SciTech Connect

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.

  13. 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.

  14. 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.

  15. Indium-111 labeled leukocyte uptake: false-positive results in noninfected pseudoaneurysms

    SciTech Connect

    Gilbert, B.R.; Cerqueira, M.D.; Vea, H.W.; Nelp, W.B.

    1986-03-01

    Indium-111 (In-111) leukocyte scintigraphy was performed in two patients with postsurgical pseudoaneurysms as part of preoperative evaluation for evidence of graft infection. Despite positive In-111 uptake by the pseudoaneurysms, surgical and pathologic examinations failed to reveal any evidence of infection. The most likely explanation for the false-positive results is the labeling of contaminating platelets and erythrocytes in the leukocyte mixture. Caution must be exercised in interpretation of In-111 leukocyte scans in patients with postsurgical pseudoaneurysms.

  16. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery.

    PubMed

    Woods, A; Patel, A; Spina, D; Riffo-Vasquez, Y; Babin-Morgan, A; de Rosales, R T M; Sunassee, K; Clark, S; Collins, H; Bruce, K; Dailey, L A; Forbes, B

    2015-07-28

    The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin nanoparticles was investigated following a single administration of 2, 20, and 390μg/mouse, showing no inflammatory response (TNF-α and IL-6, cellular infiltration and protein concentration) compared to vehicle controls at the two lower doses, but elevated mononucleocytes and a mild inflammatory effect at the highest dose tested. The biodistribution and clearance of (111)In labelled albumin solution and nanoparticles over 48h following a single pulmonary administration to mice was investigated by single photon emission computed tomography and X-ray computed tomography imaging and terminal biodistribution studies. (111)In labelled albumin nanoparticles were cleared more slowly from the mouse lung than (111)In albumin solution (64.1±8.5% vs 40.6±3.3% at t=48h, respectively), with significantly higher (P<0.001) levels of albumin nanoparticle-associated radioactivity located within the lung tissue (23.3±4.7%) compared to the lung fluid (16.1±4.4%). Low amounts of (111)In activity were detected in the liver, kidneys, and intestine at time points >24h indicating that small amounts of activity were cleared from the lungs both by translocation across the lung mucosal barrier, as well as mucociliary clearance. This study provides important information on the fate of albumin vehicles in the lungs, which may be used to direct future formulation design of inhaled nanomedicines.

  17. 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

  18. 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.

  19. Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer.

    PubMed

    Josefsson, Anders; Nedrow, Jessie R; Park, Sunju; Banerjee, Sangeeta Ray; Rittenbach, Andrew; Jammes, Fabien; Tsui, Benjamin; Sgouros, George

    2016-01-15

    The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radionuclide Indium-111 ((111)In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of (111)In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Coinjection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of (111)In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of (111)In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy.

  20. Unexpected side products in the conjugation of an amine-derivatized morpholino oligomer with p-isothiocyanate benzyl DTPA and their removal.

    PubMed

    Liu, Guozheng; Dou, Shuping; Liu, Yuxia; Liang, Minmin; Chen, Ling; Cheng, Dengfeng; Greiner, Dale; Rusckowski, Mary; Hnatowich, Donald J

    2011-02-01

    In connection with pretargeting, an amine-derivatized morpholino phosphorodiamidate oligomer (NH(2)-cMORF) was conjugated conventionally with p-isothiocyanate benzyl-DTPA (p-SCN-Bn-DTPA). However, after (111)In radiolabeling, unexpected label instability was observed. To understand this instability, the NH(2)-cMORF and, as control, the native cMORF without the amine were conjugated in the conventional manner. Surprisingly, the (111)In labeling of the native cMORF conjugate was equally effective as that of the NH(2)-cMORF conjugate (>95%) despite the absence of the amine group. Furthermore, heating the radiolabeled NH(2)-cMORF and native cMORF conjugates resulted in a 35% loss and a complete loss of the label, respectively. Since the (111)In labeled DTPA is known to be stable, the instability in both cases must be due to some unstable association of DTPA to the cMORF, presumably unstable association to some endogenous sites in cMORF. Based on this assumption, a postconjugation-prepurification heating step was introduced, and labeling efficiency and stability were again investigated. By introducing the heating step, the side products were dissociated, and after purification and labeling, the NH(2)-cMORF conjugate provided a stable label and high labeling efficiency with no need for postlabeling purification. The biodistribution of this radiolabeled conjugate in normal mice showed significantly lower backgrounds compared with the labeled unstable native cMORF conjugate. In conclusion, the conventional conjugation procedure to attach the p-SCN-Bn-DTPA to NH(2)-cMORF resulted in side product(s) that were responsible for the (111)In label instability. Adding a postconjugation-prepurification heating step dissociated the side products, improved the label stability and lowered tissue backgrounds in mice. PMID:21315270

  1. Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases

    SciTech Connect

    Patt, Y.Z.; Lamki, L.M.; Shanken, J.; Jessup, J.M.; Charnsangavej, C.; Ajani, J.A.; Levin, B.; Merchant, B.; Halverson, C.; Murray, J.L. )

    1990-07-01

    We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.

  2. 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

  3. Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas.

    PubMed

    Kryza, David; Debordeaux, Frédéric; Azéma, Laurent; Hassan, Aref; Paurelle, Olivier; Schulz, Jürgen; Savona-Baron, Catherine; Charignon, Elsa; Bonazza, Pauline; Taleb, Jacqueline; Fernandez, Philippe; Janier, Marc; Toulmé, Jean Jacques

    2016-01-01

    The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor. PMID:26901393

  4. Baboon (Papio ursinus) model to study deep vein thrombosis using 111-indium-labeled autologous platelets.

    PubMed

    Dormehl, I C; Jacobs, D J; Pretorius, J P; Maree, M; Franz, R C

    1987-01-01

    This study evaluates the chacma baboon as a model for investigations on deep vein thrombosis (DVT). There is a good correlation of the baboon and human thrombelastographic parameters (r-time, k-time, ma). Investigation on the diagnostic efficacy of 111 In-labeled platelets as an imaging agent for DVT cast considerable doubt on the procedure, owing to the age of the thrombus.

  5. 40 CFR 63.11502 - What definitions apply to this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...), subpart WW (§ 63.1061), 40 CFR 60.111b, subpart F (§ 63.101), subpart G (§ 63.111), subpart FFFF (§ 63.2550), as specified after each term: Administrator (§ 63.2) Article (40 CFR 372.3) Boiler (§ 63.111... in the CAA, § 63.2, subpart SS (§ 63.981), subpart WW (§ 63.1061), 40 CFR 60.111b, subpart F (§...

  6. Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF.

    PubMed

    Kareem, Heewa; Sandström, Karl; Elia, Ronny; Gedda, Lars; Anniko, Matti; Lundqvist, Hans; Nestor, Marika

    2010-04-01

    Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of (125)I-labeled EGF. The anti-EGFR Affibody molecule (Z(EGFR:955))(2) was then assessed as a blocking agent of (111)In-labeled EGF in a dual isotope study (50, 100, and 200 microg, preadministered 30 or 60 min before (111)In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased (125)I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 microg (Z(EGFR:955))(2) as a blocking agent 30 min before the (111)In-EGF decreased the uptake of (111)In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (Z(EGFR:955))(2) shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging. PMID:20358420

  7. 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.

  8. Coalescence of 3-phenyl-propynenitrile on Cu(111) into interlocking pinwheel chains

    NASA Astrophysics Data System (ADS)

    Luo, Miaomiao; Lu, Wenhao; Kim, Daeho; Chu, Eric; Wyrick, Jon; Holzke, Connor; Salib, Daniel; Cohen, Kamelia D.; Cheng, Zhihai; Sun, Dezheng; Zhu, Yeming; Einstein, T. L.; Bartels, Ludwig

    2011-10-01

    3-phenyl-propynenitrile (PPN) adsorbs on Cu(111) in a hexagonal network of molecular trimers formed through intermolecular interaction of the cyano group of one molecule with the aromatic ring of its neighbor. Heptamers of trimers coalesce into interlocking pinwheel-shaped structures that, by percolating across islands of the original trimer coverage, create the appearance of gear chains. Density functional theory aids in identifying substrate stress associated with the chemisorption of PPN's acetylene group as the cause of this transition.

  9. Imaging findings and pharmacokinetics of 111-indium ZME-018 monoclonal antibody (MoAb) in malignant melanoma

    SciTech Connect

    Murray, J.L.; Rosenblum, M.; Lamki, L.; Haynie, T.P.; Glenn, H.; Jahns, M.; Plager, C.; Hersh, E.M.; Unger, M.; Carlo, D.L.

    1985-05-01

    13 patients with metastatic melanoma were studied using 5 mCi of In-111 labeled MoAb ZME-018 which reacts with GP 240 melanoma-associated antigen. The MoAb was infused over 2 h at doses of 2.5 mg (5 pts), 5 mg (5 pts), and 10 mg (3 pts). Total body tomograms and planar spot views with region of interest analysis were performed at 4, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours when the background activity was less. 20 of 46 (43%) previously documented metastases were identified. More sites imaged with increasing concentrations of MoAB, I.E., 25% at 2.5 mg; 67% at 5 mg; 70% at 10 mg. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg. In two instances, uptake of 111-In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for 111-In in plasma was 24.5 +- 2.7 hours. The apparent volume of distribution (Vd) was 4.03 +- 5iota similar to the plasma value, and the calculated clearance rate for 111-In label was 0.0259 + 0.002 ml/kg/min. Mean urinary excretion of 111-In label was 8.7 +- 0.6% of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. ZME 018 was cleared more rapidly from plasma, compared to previous studies with P97 antimelanoma MoAb.

  10. Comparison of 99m technetium hexamethylpropylene-amine oxime labelled leucocyte with 111-indium tropolonate labelled granulocyte scanning and ultrasound in the diagnosis of intra-abdominal abscess.

    PubMed Central

    Weldon, M J; Joseph, A E; French, A; Saverymuttu, S H; Maxwell, J D

    1995-01-01

    Fifty patients with suspected intra-abdominal abscess were investigated prospectively with ultrasound and with 99mTc-hexamethylpropylene-amine oxime (HMPAO) isotope labelled mixed leucocytes, using 111-In tropolonate granulocyte scanning as the reference standard. Twenty five patients had inflammatory bowel disease (three were postoperative): 21 of these had Crohn's disease and four had ulcerative colitis. The remainder comprised nine with postoperative fever and 16 with fever and abdominal pain. An abscess was diagnosed when focal activity on serial 111-In tropolonate and 99m-Tc-HMPOA images at one, three, and 24 hours resulted in activity at least equal to liver activity at 24 hours. Thirteen abscesses were diagnosed using each type of white cell scanning, resulting in 100% sensitivity for 99m-Tc-HMPAO compared with 111-In tropolonate. Bowel inflammation was easily distinguished from abscess on serial images. Eight of these 13 abscesses were detected by ultrasound. Altogether 17 abscesses were found. Ultrasound detected 12, including four liver abscesses which were not purulent and had not been detected by white cell scanning. Ultrasound had a sensitivity of 71% (12 of 17) and a specificity of 87% (33 of 38) using all confirmed abscesses as the reference standard. White cell scanning showed a sensitivity of 76% (13 of 17: as a result of the four non-purulent liver abscesses) and a specificity of 100%. 99m-Tc-HMPAO scanning is as accurate as 111-In tropolonate scanning, and has several advantages including simplicity, availability, superior image quality, and reduced radiation dose. Both methods are more sensitive and specific than ultrasound for intra-abdominal abscess detection but ultrasound is advisable if a neutrophil infiltrate is not suspected. Images Figure 1 Figure 2 Figure 3 PMID:7489945

  11. Differentiation between meningiomas and other CNS tumors by simultaneous somatostatin receptor and brain scintigraphy

    SciTech Connect

    Haldemann, A.R.; Luescher, D.; Sulzer, M.

    1994-05-01

    Since the differentiation between meningiomas and some other CNS tumors may be difficult in certain localizations, biopsy is mandatory, even in patients with meningiomas who are to be treated with percutaneous radiotherapy alone. The high density of somatostatin receptors (SSR) in meningiomas has led us to compare patients with meningiomas and other CNS tumors by simultaneous SSR and brain scintigraphy (BS) using 74 MBq 111In octreotide and 740 MBq 99mTc DTPA injected two hours later. SPECT was performed on a 3-head gamma camera 4 hours after 111In octreotide injection in multiple peak acquisition mode in 35 patients with radiologically documented CNS tumors. In positive scans, a tumor ROI was defined manually in the transverse 111In slice with highest tumor contrast and the identical tumor ROI was transferred to the corresponding 99mTc slice. A SSR to BS index was then calculated from the ratio of 111In to 99mTc counts after normalizing for identical total counts in the slices. in negative scans, the SSR to BS index was set to be 1.0. In 7 meningiomas, the SSR to BS index was 2.64{plus_minus}0.76. In 28 other CNS tumors (7 gliomas I-111, 4 neurinomas, 3 glial reactions, 3 metastases, 3 gliomas IV, 2 ependymomas, 1 chordoma, 1 NHL; plus 4 inoperable, radiologically diagnosed glioblastomas) 1.06{plus_minus}0.13. Thus, a highly significant difference was found between these two groups (p<0.0001). It is concluded that combined SSR and BS allows excellent discrimination between meningiomas and other CNS tumors and may become a non-invasive alternative to biopsy in selected clinical situations.

  12. Rapid migration of /sup 111/indium-labeled granulocytes to sites of infection

    SciTech Connect

    Dutcher, J.P.; Schiffer, C.A.; Johnston, G.S.

    1981-03-05

    Results are reported of studies with homologous, ABO-matched, /sup 111/In-labeled granulocytes given to 14 granulocytopenic patients with specific, known sites of infection. In 13 of these patients, radioactivity was noted at the site of infection after only 30 minutes. Subsequent scans at four hours or 24 hours or both were all positive at the same site. This technique provides a method for rapid diagnosis of occult infection in this patient population.

  13. 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.

  14. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging

    SciTech Connect

    Datz, F.L.; Thorne, D.A.

    1987-05-01

    Although photon deficient defects on bone scan have received a great deal of interest, such defects in bones on Indium-111 (/sup 111/In) leukocyte imaging have not been as well recognized. We therefore undertook a retrospective review to determine the frequency and significance of such cold defects on /sup 111/In-labeled leukocyte imaging. Three hundred thirty-two scans on 290 patients were reviewed and 40 cases of decreased activity involving bone were found, for an incidence of 12%. The causes of the defects were: fracture (eight), nontraumatic avascular necrosis (eight), solid tumor (six), prostheses and other orthopedic hardware (four), advanced age (four), radiation (three), leukemia (two), osteomyelitis (two), myelofibrosis (one), postlaminectomy (one), and idiopathic (one). To determine the frequency of cold defects in osteomyelitis, all 15 cases of osteomyelitis in this series were reviewed and 12 showed increased activity, two were cold, and one was normoactive. Thus, 14% of cases of osteomyelitis presented as cold defects. We conclude that cold bone defects do occur on /sup 111/In-labeled leukocyte scans and that the causes of such defects are similar to those reported for bone and bone marrow scanning.

  15. Characterization of ZnO and Zn0.95Co0.05O prepared by sol-gel method using PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Mercurio, M. E.; Carbonari, A. W.; Cordeiro, M. R.; Saxena, R. N.

    The measurement of the electric field gradient (efg) with PAC spectroscopy was used to follow the heat treatment during the preparation of ZnO samples using sol-gel method. In particular, the investigation was carried out on samples of intrinsically n-type II-VI wurtzite semiconductor ZnO and Co-doped Zn0.95Co0.05O samples prepared by sol-gel methodology from pure metallic Zn(99.9999%). Carrier-free 111In nuclei were introduced in the samples by thermal diffusion. 111In solution was added to the precursor sol-gel solution prior to the formation of gel material. PAC measurements were carried out to follow the formation of the ZnO. Two undoped ZnO samples, which were heated in air and argon atmosphere, show different results. PAC measurements were also used to follow the 111In diffusion in a commercially purchased ZnO (99.99%) sample as well as to compare the results with the measurements taken with sol-gel prepared samples. The results show that samples prepared by sol-gel process followed by heating in argon produce better quality ZnO samples. The results also show that the Co atoms in Zn0.95Co0.05O are in substitutional sites.

  16. Characterization of ZnO and Zn0.95Co0.05O prepared by sol-gel method using PAC spectroscopy

    NASA Astrophysics Data System (ADS)

    Mercurio, M. E.; Carbonari, A. W.; Cordeiro, M. R.; Saxena, R. N.

    2007-07-01

    The measurement of the electric field gradient (efg) with PAC spectroscopy was used to follow the heat treatment during the preparation of ZnO samples using sol-gel method. In particular, the investigation was carried out on samples of intrinsically n-type II-VI wurtzite semiconductor ZnO and Co-doped Zn0.95Co0.05O samples prepared by sol-gel methodology from pure metallic Zn(99.9999%). Carrier-free 111In nuclei were introduced in the samples by thermal diffusion. 111In solution was added to the precursor sol-gel solution prior to the formation of gel material. PAC measurements were carried out to follow the formation of the ZnO. Two undoped ZnO samples, which were heated in air and argon atmosphere, show different results. PAC measurements were also used to follow the 111In diffusion in a commercially purchased ZnO (99.99%) sample as well as to compare the results with the measurements taken with sol-gel prepared samples. The results show that samples prepared by sol-gel process followed by heating in argon produce better quality ZnO samples. The results also show that the Co atoms in Zn0.95Co0.05O are in substitutional sites.

  17. Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods

    SciTech Connect

    Vallabhajosula, S.; Machac, J.; Goldsmith, S.J.; Lipszyc, H.; Badimon, L.; Rand, J.; Fuster, V.

    1986-11-01

    The effect of labeling media on the kinetics of(/sup 111/In)platelets was evaluated by performing a paired crossover study in eight normal human subjects using tropolone and oxine methods. Platelets were labeled in autologous plasma with (/sup 111/In)tropolone (In-tr) and in ACD-saline with (/sup 111/In)oxine (In-ox) and reinjected. Starting at 1 hr, ten blood samples were obtained over an 8-day period. The in vivo platelet recovery was higher at 1 hr and throughout the 8 days of study with In-tr and the gamma camera images showed less uptake in liver and spleen than with In-ox. When platelet life-span (PLS) was estimated using all ten samples, only linear regression showed that the platelet life-span was longer with In-tr (10.7 +/- 1.5) than with In-ox (9.5 +/- 0.8). When the PLS was estimated excluding the 1-hr sample point, the life-span of platelets was significantly longer with In-tr than with In-ox based on three out of four models of curve fitting. These results demonstrate that platelets labeled with In-tr in plasma are preserved better in circulation and have equal or longer life-span than platelets labeled with In-ox in ACD-saline.

  18. Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods.

    PubMed

    Vallabhajosula, S; Machac, J; Goldsmith, S J; Lipszyc, H; Badimon, L; Rand, J; Fuster, V

    1986-11-01

    The effect of labeling media on the kinetics of[111In]platelets was evaluated by performing a paired crossover study in eight normal human subjects using tropolone and oxine methods. Platelets were labeled in autologous plasma with [111In]tropolone (In-tr) and in ACD-saline with [111In]oxine (In-ox) and reinjected. Starting at 1 hr, ten blood samples were obtained over an 8-day period. The in vivo platelet recovery was higher at 1 hr and throughout the 8 days of study with In-tr and the gamma camera images showed less uptake in liver and spleen than with In-ox. When platelet life-span (PLS) was estimated using all ten samples, only linear regression showed that the platelet life-span was longer with In-tr (10.7 +/- 1.5) than with In-ox (9.5 +/- 0.8). When the PLS was estimated excluding the 1-hr sample point, the life-span of platelets was significantly longer with In-tr than with In-ox based on three out of four models of curve fitting. These results demonstrate that platelets labeled with In-tr in plasma are preserved better in circulation and have equal or longer life-span than platelets labeled with In-ox in ACD-saline.

  19. 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.

  20. Lipid-Calcium Phosphate Nanoparticles for Delivery to the Lymphatic System and SPECT/CT Imaging of Lymph Node Metastases

    PubMed Central

    Tseng, Yu-Cheng; Xu, Zhenghong; Guley, Kevin; Yuan, Hong; Huang, Leaf

    2014-01-01

    A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter ~25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of 111In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted 111In-LCP preferentially accumulated in the lymph nodes at ~70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only ~25% ID/g. Larger LCP (diameter ~67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected 111In-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed. PMID:24613050

  1. Pulmonary clearance of three aerosolized solutes in oleic acid-induced lung injury

    SciTech Connect

    Huchon, G.J.; Montgomery, A.B.; Lipavsky, A.; Hoeffel, J.M.; Murray, J.F.

    1988-03-01

    We studied the effects of oleic acid (OA) on pulmonary clearance of three aerosolized radioactive solutes: /sup 99m/Tc-diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA), /sup 67/Ga-desferoxamine (/sup 67/Ga-DFOM), and /sup 111/In-transferrin (/sup 111/In-TF). Either 0.09 ml/kg OA or an equivalent volume of 0.9% NaCl (controls) was administered intravenously to 48 anesthetized, paralyzed dogs. Each animal received one aerosolized solute either 60 min after (protocol A) or 30 min before (protocol B) the infusion of OA or NaCl. In protocol A clearances of all three solutes were similar in OA and control animals. In contrast, in protocol B clearances of all three solutes increased significantly during OA infusion; during the next 60 min clearances of /sup 99m/Tc-DTPA and /sup 67/Ga-DFOM returned to control values but 111In-TF remained increased. We conclude that 1) in OA-induced permeability edema pulmonary clearance of aerosolized solutes is increased when the aerosol is delivered 30 min before but not 60 min after injury, and 2) increased clearance persists only for large molecules, presumably because smaller molecules cross injured epithelium quickly and completely. These phenomena are best explained by a nonhomogeneous distribution of OA-induced injury.

  2. SEMICONDUCTOR PHYSICS: Effects of Sn-doping on morphology and optical properties of CdTe polycrystalline films

    NASA Astrophysics Data System (ADS)

    Jin, Li; Linyu, Yang; Jikang, Jian; Hua, Zou; Yanfei, Sun

    2009-11-01

    Sn-doped CdTe polycrystalline films were successfully deposited on ITO glass substrates by close space sublimation. The effects of Sn-doping on the microstructure, surface morphology, and optical properties of polycrystalline films were studied using X-ray diffraction, scanning electron microscopy, and ultraviolet-visible spectrophotometry, respectively. The results show that the lower molar ratio of Sn and CdTe conduces to a strongly preferential orientation of (111) in films and a larger grain size, which indicates that the crystallinity of films can be improved by appropriate Sn-doping. As the molar ratio of Sn and CdTe increases, the preferential orientation of (111) in films becomes weaker, the grain size becomes smaller, and the crystal boundary becomes indistinct, which indicates that the crystallization growth of films is incomplete. However, as the Sn content increases, optical absorption becomes stronger in the visible region. In summary, a strongly preferential orientation of (111) in films and a larger grain size can be obtained by appropriate Sn-doping (molar ratio of Sn : CdTe = 0.06 : 1), while the film retains a relatively high optical absorption in the visible region. However, Sn-doping has no obvious influence on the energy gap of CdTe films.

  3. Block copolymer micelles target Auger electron radiotherapy to the nucleus of HER2-positive breast cancer cells.

    PubMed

    Hoang, Bryan; Reilly, Raymond M; Allen, Christine

    2012-02-13

    Intracellular trafficking of Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. In the present study, block copolymer micelles (BCMs) were labeled with the Auger electron emitter indium-111 ((111)In) and loaded with the radiosensitizer methotrexate. HER2 specific antibodies (trastuzumab fab) and nuclear localization signal (NLS; CGYGPKKKRKVGG) 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 and intracellular distribution of the multifunctional BCMs were evaluated in a panel of breast cancer cell lines with different levels of HER2 expression. Indeed cell uptake was found to be HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS peptides to the surface of BCMs was found to result in a significant increase in nuclear uptake of the radionuclide (111)In. Successful nuclear targeting was shown to improve the antipoliferative effect of the Auger electrons as measured by clonogenic assays. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and (111)In in all breast cancer cell lines evaluated.

  4. 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

  5. Indium-111-labeled granulocyte head accumulation in patients with Wegener's granulomatosis.

    PubMed

    Roccatello, D; Picciotto, G; Gigliola, G; Cacace, G; Rollino, C; Quattrocchio, G; Funaro, L; De Filippi, P G; Piccoli, G

    1995-01-01

    Among the symptoms of systemic vasculitis, purulent rhinorrhea with painful sinusitis is thought to be relatively specific to Wegener's granulomatosis (WG). Sixteen patients with rapidly progressive glomerulonephritis (GN), arteritis and extensive crescents in renal biopsy were studied by head indium-111 (111In)-granulocyte scanning. They included 8 WG, 5 microscopic polyarteritis, 2 necrotizing and crescentic GN and 1 classic polyarteritis nodosa. Autologous granulocytes labeled with 12.3 MBq of 111In-oxine were administered intravenously. Scintigraphic studies were performed at 4 and 24 h post-injection. Compared to the non-WG cases, considered as a whole, significant accumulation of tracer in sinuses was observed in WG patients (Fisher's p = 0.02). Substantial scintigraphic amelioration was obtained in a WG case treated with methylprednisolone pulses and, in another WG case, after high doses of intravenous gamma-globulins. The complete disappearance of facial uptake was obtained after 2 months of intensive therapy (i.e., steroid, cyclophosphamide and plasma exchange) in another WG patient. 111In-oxine granulocyte imaging may be useful in clinical practice as an additional marker of disease activity and a tool of identification of upper respiratory tract involvement.

  6. Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

    SciTech Connect

    Srivastava, S.C.; Mease, R.C.; Meinken, G.E.; Mausner, L.F.; Steplewski, Z.

    1988-01-01

    High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs.

  7. 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.

  8. Development of PEGylated Cysteine-Modified Lysine Dendrimers with Multiple Reduced Thiols To Prevent Hepatic Ischemia/Reperfusion Injury.

    PubMed

    Katsumi, Hidemasa; Nishikawa, Makiya; Hirosaki, Rikiya; Okuda, Tatsuya; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru; Sakane, Toshiyasu; Yamamoto, Akira

    2016-08-01

    To inhibit hepatic ischemia/reperfusion injury, we developed polyethylene glycol (PEG) conjugated (PEGylated) cysteine-modified lysine dendrimers with multiple reduced thiols, which function as scavengers of reactive oxygen species (ROS). Second, third, and fourth generation (K2, K3, and K4) highly branched amino acid spherical lysine dendrimers were synthesized, and cysteine (C) was conjugated to the outer layer of these lysine dendrimers to obtain K2C, K3C, and K4C dendrimers. Subsequently, PEG was reacted with the C residues of the dendrimers to obtain PEGylated dendrimers with multiple reduced thiols (K2C-PEG, K3C-PEG, and K4C-PEG). Radiolabeled K4C-PEG ((111)In-K4C-PEG) exhibited prolonged retention in the plasma, whereas (111)In-K2C-PEG and (111)In-K3C-PEG rapidly disappeared from the plasma. K4C-PEG significantly prevented the elevation of plasma alanine aminotransferase (ALT) activity, an index of hepatocyte injury, in a mouse model of hepatic ischemia/reperfusion injury. In contrast, K2C-PEG, K3C-PEG, l-cysteine, and glutathione, the latter two of which are classical reduced thiols, hardly affected the plasma ALT activity. These findings indicate that K4C-PEG with prolonged circulation time is a promising compound to inhibit hepatic ischemia/reperfusion injury. PMID:27336683

  9. 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.

  10. From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

    PubMed Central

    Pawlak, Dariusz; Rangger, Christine; Peitl, Petra Kolenc; Garnuszek, Piotr; Maurin, Michał; Ihli, Laura; Kroselj, Marko; Maina, Theodosia; Maecke, Helmut; Erba, Paola; Kremser, Leopold; Hubalewska-Dydejczyk, Alicja; Mikołajczak, Renata; Decristoforo, Clemens

    2016-01-01

    Introduction A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA–DGlu–DGlu–DGlu–DGlu–DGlu–DGlu– Ala–Tyr–Gly–Trp–Met–Asp–Phe–NH2 (CP04) after labelling with 111In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze-dried formulation of the precursor CP04 for a first multi-centre clinical trial with 111In-CP04 in MTC patients. Materials and methods The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 μg) were prepared and radiolabelled with 111In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. Results Use of ascorbic acid buffer (pH 4.5) allowed freeze-drying of the kit formulation with satisfactory pellet-formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met11-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 μg formulation. The final formulations contained 10 or 50 μg CP04, 25 mg ascorbic acid, 0.5 mg gentisic acid and 5 mg l-methionine. The radiolabelling performed by incubation of 200–250 MBq 111InCl3 at 90 °C for 15 min resulted in reproducible radiochemical purity (RCP) >94%. Kit-stability was proven for >6

  11. Effect of tumor mass and antigenic nature on the biodistribution of labeled monoclonal antibodies in mice

    SciTech Connect

    Watanabe, Y.; Endo, K.; Koizumi, M.; Kawamura, Y.; Saga, T.; Sakahara, H.; Kuroki, M.; Matsuoka, Y.; Konishi, J.

    1989-06-01

    The effect of tumor mass and antigenic nature on the biodistribution of 111In- and 125I-labeled monoclonal antibodies (MoAbs) was studied using F(ab')2 fragments of three representative anti-tumor MoAbs and SW1116 human colorectal carcinoma grown in nude mice. The 19-9, F33-104 anti-CEA, and 17-1A MoAbs showed specific binding to SW1116 cells. The former two MoAbs recognize circulating CA 19-9 with molecular weights of more than 5,000,000 and CEA of Mr 170,000-180,000, respectively, whereas 17-1A reacts with a nonshedding antigen. Both percentage injected dose per gram tumor and tumor-to-blood ratios were inversely proportional to the tumor mass in nude mice administered 111In- and 125I-labeled 19-9, but liver uptake increased as tumor size increased. Analysis of serum samples and tumor homogenates demonstrated the presence of a high-molecular-weight species, probably due to the antibody binding to CA 19-9. In the case of 111In-labeled anti-CEA MoAb, tumor uptake also decreased and liver uptake increased with tumor size, but this effect was less obvious than that of 19-9. In contrast, tumor and liver uptake of 125I-labeled anti-CEA MoAb, 111In- and 125I-labeled 17-1A and control antibodies were independent of tumor mass. The absolute tumor uptake and tumor-to-blood ratios of all 125I-labeled antibodies were lower than those of the 111In-labeled ones. And the effect of tumor mass was also weaker with 125I-labeled antibodies, probably due to in vivo dehalogenation. These results indicate that the effect of tumor size on the incorporation of labeled MoAb into tumors is dependent on the antigenic nature to be targeted and/or radionuclides used for labeling and that high concentrations of circulating high molecular weight antigens may limit in vivo use of MoAb conjugates.

  12. 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

  13. (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

  14. 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.

  15. 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.

  16. 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).

  17. 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).

  18. On the existence of ordered organic adlayers at the Cu(111)/electrolyte interface.

    PubMed

    Friebel, Daniel; Mangen, Thomas; Obliers, Britta; Schlaup, Christian; Broekmann, Peter; Wandelt, Klaus

    2004-03-30

    We have reinvestigated the behavior of a Cu(111) electrode in pure and cinchonidine containing aqueous 0.1 M HClO4 solution by cyclic voltammetry (CV) and in situ electrochemical scanning tunneling microscopy (STM). In contrast to previous publications by Wan et al. (Langmuir 2000, 19, 1958-1962 and references cited therein) on Cu(111) in pure 0.1 M HClO4 which claimed an adsorbate-free Cu(111) surface in the entire potential range, we have found a highly ordered hexagonal adsorbate structure with a (4 x 4) unit cell, which is stable in the potential range from hydrogen evolution at -350 to -150 mV (RHE). The adsorbate-free (1 x 1) Cu(111) surface is only visible in a fairly small potential range from -150 to +50 mV. A disordered surface structure is formed at more positive potentials which is interpreted by adsorption of an oxygen-containing species. Furthermore, the formation of a highly ordered cinchonidine adlayer on Cu(111) in 0.1 M HClO4 as reported by Wan et al. (J. Am. Chem. Soc. 2002, 124, 14300-14301) could not be reproduced here. In fact, the similarity of all structures reported by Wan et al. for a great variety of different organic adlayers on Cu(111) in HClO4 solution including cinchonidine with the (4 x 4) superstructure found here already in pure HClO4 solution (i.e., without organic solute) casts serious doubts on the validity of those previous results by Wan et al. in general.

  19. Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma

    SciTech Connect

    Sandrock, D.; Blossey, H.C.; Steinroeder, M.; Munz, D.L.

    1989-01-01

    We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG.

  20. Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab')2 fragments of an anti-carcinoembryonic antigen monoclonal antibody: A multicenter study

    SciTech Connect

    Siccardi, A.G.; Buraggi, G.L.; Callegaro, L.; Colella, A.C.; De Filippi, P.G.; Galli, G.; Mariani, G.; Masi, R.; Palumbo, R.; Riva, P. )

    1989-06-01

    F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody F023C5, determined to be more suitable than intact IgG and Fab fragments for immunoscintigraphy, were labeled with 131I or conjugated to DTPA for instant 111In-labeling, and administered i.v. (2-3 mCi/0.5 mg) to 509 patients in 11 nuclear medicine departments: 284 patients had gastrointestinal adenocarcinomas, 204 had nongastrointestinal adenocarcinomas and 21 were control; serum CEA was elevated in 169 patients, normal in 115, and not determined in 225. The following results were obtained: (a) no adverse reactions; (b) tumor imaging in 324 patients (in particular, in 81.5% CEA-seropositive and in 69.0% CEA-seronegative patients); (c) no significant difference in sensitivity among the results of the 11 departments; (d) no significant difference in overall sensitivity between 131I-and 111In-labeled immunoradiopharmaceuticals; (e) the fraction of documented lesions imaged was 73.3% in CEA-seropositive and 53.7% in CEA-seronegative patients; (f) the detection of liver metastases was hampered, particularly when using the 111In-labeled reagent, by nonspecific radioactivity uptake; (g) the major cause of negative immunoscintigraphy results was a lack of CEA in tumor lesions, as documented by immunohistochemistry; (h) lesion size is also important since the sensitivity was 64% for lesions up to 2 cm in diameter and 84% for larger lesions; (i) many unexpected radiolocalizations were recorded. Most were identified as occult tumor lesions. In 35 patients, this finding contributed to the early detection of tumor recurrences.

  1. Synthesis, characterization, and evaluation of radiometal-containing peptide nucleic acids.

    PubMed

    Stephan, Holger; Foerster, Christian; Gasser, Gilles

    2014-01-01

    Peptide nucleic acids (PNAs) have very attractive properties for applications in nuclear medicine. Because PNAs have high selectivity for DNA/RNA recognition, resistance to nuclease/protease degradation, and high thermal and radiolytic stabilities, PNA bioconjugates could transform the areas of diagnostic and therapeutic nuclear medicine. In this book chapter, we report on the current developments towards the preparation of radiometal-containing PNA constructs and summarize the protocols for labeling these probes with (99m)Tc, (111)In, (64)Cu, (90)Y, and (177)Lu.

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

    PubMed Central

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

    2016-01-01

    Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID:26848870

  3. Preparation of TiO2 nanocrystallites by oxidation of Ti-Au111 surface alloy.

    PubMed

    Potapenko, Denis V; Osgood, Richard M

    2009-06-01

    Ti-Au surface alloy oxidation is used to form nanocrystals of TiO(2) on Au(111). In situ scanning tunneling microscopy (STM) studies show that the approach yields arrays of 8-11 nm wide crystals with relatively narrow size dispersion and uniform crystallography. STM imaging shows that their crystallographic form is rutile with a triangular or hexagonal geometry. Scanning tunneling spectroscopy indicates that the crystals have a well-developed band gap, comparable to that in bulk TiO(2).

  4. 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.

  5. 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.

  6. 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.

  7. Electric field gradients at indium sites in spinels measured by perturbed angular correlations

    NASA Astrophysics Data System (ADS)

    Pasquevich, A. F.

    2005-07-01

    The Electric Field Gradient (EFG) at 111Cd isotope (produced by the Electron Capture (EC) decay of 111In) has been measured using Perturbed Angular Correlations (PAC) technique in many spinels. In the present work, data arising from such experiments were collected. The experimental EFG values, obtained at room temperature, at the B site of normal spinels are compared with those calculated considering the monopole moment of the ions and the dipole polarization of the anions. This comparison allows the determination of the u-parameter, which gives the anion position in the lattice.

  8. Characteristic interactions of 111Cd probes with nonradioactive In impurities doped in ZnO

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    Local structures produced in 0.5 at.% In-doped ZnO were investigated by means of the time-differential perturbed angular correlation method using the 111Cd probe nuclei generated in the disintegration of different parents, 111In and 111mCd. From distinct perturbation patterns obtained with the probes descended from the different parents, it was ascertained that the doped In atoms locally form a unique structure dispersed in ZnO matrix without forming macroscopic agglomerates of their own.

  9. Influence of formulation variables on the biodistribution of multifunctional block copolymer micelles.

    PubMed

    Fonge, Humphrey; Huang, Huang; Scollard, Deborah; Reilly, Raymond M; Allen, Christine

    2012-02-10

    The physico-chemical characteristics and composition of block copolymer micelles (BCMs) may influence the pharmacokinetics and consequently, the desired delivery characteristics. In this study the influence of formulation variables such as size, density of targeting ligand [i.e. epidermal growth factor (hEGF)] and the bifunctional chelator (BFC) used for labelling the BCMs with (111)In, on the pharmacokinetics and biodistribution in mice were evaluated. BCMs were prepared from Me-PEG(x)-b-PCL(y) (x=2.5 k, y=1.2 k for 15 nm BCMs and x=5 k, y=5 k for 60 nm BCMs) with (targeted, 1 or 5 mol% hEGF) or without (non-targeted) hEGF-PEG(x)-b-PCL(y). To investigate the effect of the BFC on the pharmacokinetics, the BCMs were labelled with (111)In using p-SCN-Bn-DOTA (Bn-DOTA-PEG(x)-b-PCL(y)), H(2)N-DOTA (DOTA-PEG(x)-b-PCL(y)), DTPA anhydride (DTPA-PEG(x)-b-PCL(y)) or p-SCN-Bn-DTPA (Bn-DTPA-PEG(x)-b-PCL(y)). The resulting 15 nm or 60 nm non-targeted or targeted (1 or 5 mol% hEGF) were injected via a tail vein to mice bearing MDA-MB-468 human breast cancer xenograft that overexpress EGFR, followed by pharmacokinetics and biodistribution studies. Pharmacokinetic parameters were determined by fitting the blood concentration vs time data using a two compartment model with i.v. bolus input. Pharmacokinetic parameters were found to depend on BCM size, the BFC used as well as the density of hEGF on the surface of the BCMs. BCMs labelled with p-SCN-Bn-DTPA ((111)In-Bn-BCMs) showed improved pharmacokinetics (i.e. extended circulation lifetime) and tumor uptake compared to those labelled with DOTA-PEG(x)-b-PCL(y), p-SCN-Bn-DOTA or DTPA dianhydride. Formulations with a high density of hEGF (5 mol% hEGF) had short circulation half-lives. BCMs labelled with (111)In via p-SCN-Bn-DTPA showed highest accumulation in the liver and spleen and slower whole body elimination. Smaller sized BCMs were rapidly cleared from the circulation. Increasing the density of hEGF on the surface did not

  10. Selection of optimal chelator improves the contrast of GRPR imaging using bombesin analogue RM26.

    PubMed

    Mitran, Bogdan; Varasteh, Zohreh; Selvaraju, Ram Kumar; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Tolmachev, Vladimir; Rosenström, Ulrika; Orlova, Anna

    2016-05-01

    Bombesin (BN) analogs bind with high affinity to gastrin-releasing peptide receptors (GRPRs) that are up-regulated in prostate cancer and can be used for the visualization of prostate cancer. The aim of this study was to investigate the influence of radionuclide-chelator complexes on the biodistribution pattern of the 111In-labeled bombesin antagonist PEG2-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (PEG2-RM26) and to identify an optimal construct for SPECT imaging. A series of RM26 analogs N-terminally conjugated with NOTA, NODAGA, DOTA and DOTAGA via a PEG2 spacer were radiolabeled with 111In and evaluated both in vitro and in vivo. The conjugates were successfully labeled with 111In with 100% purity and retained binding specificity to GRPR and high stability. The cellular processing of all compounds was characterized by slow internalization. The IC50 values were in the low nanomolar range, with lower IC50 values for positively charged natIn-NOTA-PEG2-RM26 (2.6 ± 0.1 nM) and higher values for negatively charged natIn-DOTAGA-PEG2-RM26 (4.8 ± 0.5 nM). The kinetic binding studies showed KD values in the picomolar range that followed the same pattern as the IC50 data. The biodistribution of all compounds was studied in BALB/c nu/nu mice bearing PC-3 prostate cancer xenografts. Tumor targeting and biodistribution studies displayed rapid clearance of radioactivity from the blood and normal organs via kidney excretion. All conjugates showed similar uptake in tumors at 4 h p.i. The radioactivity accumulation in GRPR-expressing organs was significantly lower for DOTA- and DOTAGA-containing constructs compared to those containing NOTA and NODAGA. 111In-NOTA-PEG2-RM26 with a positively charged complex showed the highest initial uptake and the slowest clearance of radioactivity from the liver. At 4 h p.i., DOTA- and DOTAGA-coupled analogs showed significantly higher tumor-to-organ ratios compared to NOTA- and NODAGA-containing variants. The NODAGA conjugate demonstrated the

  11. Measurements of Aluminum Combustion in Energetic Formulations

    NASA Astrophysics Data System (ADS)

    Miller, J. Scott; Pangilinan, G. I.

    2004-07-01

    Aluminum combustion plays an important role in tailoring energy release rates of energetic materials. The intimate mixing between Al and oxidizers from the formulation itself or from the surrounding atmosphere is key to effecting combustion. We infer combustion processes in detonated aluminized energetic formulations PBXIH-135 and PBXN-111 in air using time-resolved spectroscopy. We recorded spectral emissions from Al and AlO emanating from the surface of each sample for up to 100 μs. We observe differences in metal combustion between the oxidizer deficient PBXIH-135 and the oxygen-rich PBXN-111. We will discuss phases of combustion that each formulation exhibits and possible reaction processes.

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

    DOE PAGES

    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.

  13. Antibody mass escalation study in patients with castration resistant prostate cancer using 111I-J591: Lesion detectability and dosimetric projections for 90Y radioimmunotherapy

    PubMed Central

    Pandit-Taskar, Neeta; O’Donoghue, Joseph A.; Morris, Michael J; Wills, Eze A.; Schwartz, Lawrence H.; Gonen, Mithat; Scher, Howard I.; Larson, Steven M.; Divgi, Chaitanya R.

    2009-01-01

    Background J591, a monoclonal antibody that targets the external domain of the prostate specific membrane antigen (PSMA), has potential as an agent for radioimmunotherapy. A pilot trial was carried out in patients with prostate cancer using repetitive administrations of escalating masses of J591. An analysis was carried out to assess (1) lesion detectability by 111InJ591 gamma camera imaging compared to standard imaging methods and (2) the effect of increasing antibody mass on lesion detectability, biodistribution and dosimetry. Methods Fourteen patients with metastatic prostate cancer received escalating amounts (10, 25, 50 and 100 mg) of J591 in a series of administrations each separated by 3 weeks. All antibody administrations included a fixed amount of radiolabeled antibody 111In-DOTA-J591 (2mg of J591 labeled with 185MBq (5 mCi) of 111In via the chelating agent DOTA). Three whole body gamma camera scans with at least one SPECT scan together with multiple whole body count-rate measurements and serum activity concentration measurements were obtained in all patients. Images were analyzed for distribution and lesion targeting. Estimates of clearance rates and liver and lesion uptake were made for each treatment cycle. These estimates were used to generate dosimetric projections for radioimmunotherapy with 90Y-labeled J591. Results A total of 80 lesions in 14 patients were detected. Both skeletal and soft tissue disease was targeted by the antibody as seen on 111In-J591 scans. Antibody localized to 93.7% of skeletal lesions detected by conventional imaging. Clearance of radioactivity from whole body, serum and liver was dependent on antibody mass. Normalized average values of the ratio of residence times between lesion and liver for 10, 25, 50 and 100mg of antibody were 1.0, 1.9, 3.2 and 4.0 respectively. Dosimetric projections for radioimmunotherapy with 90Y-labeled J591 suggested similar absorbed doses to lesions, for treatment at the maximally tolerated activity

  14. Effect of long-time, elevated-temperature exposures to vacuum and lithium on the properties of a tantalum alloy, T-111

    NASA Technical Reports Server (NTRS)

    Buzzard, R. J.; Sheffler, K. D.

    1974-01-01

    The effect of long-term, elevated-temperature vacuum and lithium exposures on the mechanical properties of T-111 (Ta-8W-2Hf) is determined. Exposure conditions were for 1000 hours at 980 or 1315 C, 5000 hours at 1315 C, and a duplex temperature exposure of 1000 hours at 980 C plus 4000 hours at 1040 C. The exposures resulted in reduced tensile and creep strengths of the T-111 in the 900 to 1100 C temperature range where a dynamic strain-age-strengthening mechanism is operative in this alloy. This strength reduction was attributed to the depletion of oxygen from solid solution in this alloy.

  15. 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.

  16. Investigation of the relationship between linear attenuation coefficients and CT Hounsfield units using radionuclides for SPECT.

    PubMed

    Brown, Saxby; Bailey, Dale L; Willowson, Kathy; Baldock, Clive

    2008-09-01

    This study has investigated the relationship between linear attenuation coefficients (mu) and Hounsfield units (HUs) for six materials covering the range of values found clinically. Narrow-beam mu values were measured by performing radionuclide transmission scans using (99m)Tc, (123)I, (131)I, (201)Tl and (111)In. The mu values were compared to published data. The relationships between mu and HU were determined. These relationships can be used to convert computed tomography (CT) images to mu-maps for single photon emission computed tomography (SPECT) attenuation correction. PMID:18662614

  17. Probing the ultrafast electron transfer at the CuPc/Au(111) interface

    SciTech Connect

    Chen Wei; Wang Li; Qi Dongchen; Chen Shi; Gao Xingyu; Wee, Andrew Thye Shen

    2006-05-01

    Core-hole clock spectroscopy and near-edge x-ray-absorption fine structure measurements have been used to investigate the ultrafast electron transfer dynamics at the Copper(II) phthalocyanine (CuPc)/Au(111) interface. It was found that the strong electronic coupling between the first layer of CuPc molecules and Au(111) substrate favors ultrafast electron transfer from the lowest unoccupied molecular orbital of the CuPc molecules to the conduction band of Au(111) in the time scale of {approx}6 fs. In contrast, the intermolecular electron transfer within multilayers of CuPc molecules via the weak van der Waals interaction was much slower.

  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. 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

  20. Polymeric micelles as carriers of diagnostic agents.

    PubMed

    Trubetskoy

    1999-04-01

    This review deals with diagnostic applications of polymeric micelles composed of amphiphilic block-copolymers. In aqueous solutions these polymers spontaneously form particles with diameter 20-100 nm. A variety of diagnostic moieties can be incorporated covalently or non-covalently into the particulates with high loads. Resulting particles can be used as particulate agents for diagnostic imaging using three major imaging modalities: gamma-scintigraphy, magnetic resonance imaging and computed tomography. The use of polyethyleneoxide-diacyllipid micelles loaded with chelated (111)In/Gd(3+) as well as iodine-containing amphiphilic copolymer in percutaneous lymphography and blood pool/liver imaging are discussed as specific examples.

  1. Detection of subdural empyema with radionuclides

    SciTech Connect

    McKillop, J.H.; Holtzman, D.S.; McDougall, I.R.

    1980-06-01

    Computed tomography (CT) is now the standard method of confirming a diagnosis of suspected subdural empyema. We report a case in which the radionuclide brain scan was abnormal at a time when the CT scan was normal. An /sup 111/In-labeled leukocyte scan was also performed in this patient and demonstrated abnormal uptake in the empyema. The scintigraphic findings in a second case of subdural empyema are also described. The relative roles of radionuclide studies and CT scans in the patient with suspected subdural empyema are discussed.

  2. Increasing the Net Negative Charge by Replacement of DOTA Chelator with DOTAGA Improves the Biodistribution of Radiolabeled Second-Generation Synthetic Affibody Molecules.

    PubMed

    Westerlund, Kristina; Honarvar, Hadis; Norrström, Emily; Strand, Joanna; Mitran, Bogdan; Orlova, Anna; Eriksson Karlström, Amelie; Tolmachev, Vladimir

    2016-05-01

    A promising strategy to enable patient stratification for targeted therapies is to monitor the target expression in a tumor by radionuclide molecular imaging. Affibody molecules (7 kDa) are nonimmunoglobulin scaffold proteins with a 25-fold smaller size than intact antibodies. They have shown an apparent potential as molecular imaging probes both in preclinical and clinical studies. Earlier, we found that hepatic uptake can be reduced by the incorporation of negatively charged purification tags at the N-terminus of Affibody molecules. We hypothesized that liver uptake might similarly be reduced by positioning the chelator at the N-terminus, where the chelator-radionuclide complex will provide negative charges. To test this hypothesis, a second generation synthetic anti-HER2 ZHER2:2891 Affibody molecule was synthesized and labeled with (111)In and (68)Ga using DOTAGA and DOTA chelators. The chelators were manually coupled to the N-terminus of ZHER2:2891 forming an amide bond. Labeling DOTAGA-ZHER2:2891 and DOTA-ZHER2:2891 with (68)Ga and (111)In resulted in stable radioconjugates. The tumor-targeting and biodistribution properties of the (111)In- and (68)Ga-labeled conjugates were compared in SKOV-3 tumor-bearing nude mice at 2 h postinjection. The HER2-specific binding of the radioconjugates was verified both in vitro and in vivo. Using the DOTAGA chelator gave significantly lower radioactivity in liver and blood for both radionuclides. The (111)In-labeled conjugates showed more rapid blood clearance than the (68)Ga-labeled conjugates. The most pronounced influence of the chelators was found when they were labeled with (68)Ga. The DOTAGA chelator gave significantly higher tumor-to-blood (61 ± 6 vs 23 ± 5, p < 0.05) and tumor-to-liver (10.4 ± 0.6 vs 4.5 ± 0.5, p < 0.05) ratios than the DOTA chelator. This study demonstrated that chelators may be used to alter the uptake of Affibody molecules, and most likely other scaffold-based imaging probes, for improvement

  3. 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.

  4. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    PubMed

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  5. Nuclear Imaging of Amyloidosis

    PubMed Central

    Cytawa, Wojciech; Teodorczyk, Jacek; Lass, Piotr

    2014-01-01

    Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. 123I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. 99mTc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as 201Tl, 123I-mIBG, together with 111In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. 67Ga-citrate and 99mTc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with 131I or 111In. Among PET tracers, 11C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge. PMID:25071873

  6. Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

    SciTech Connect

    Datz, F.L.; Thorne, D.A.

    1986-12-01

    Although /sup 111/In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan. Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified. Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed. The overall sensitivity, considering all 312 studies, was 90%. One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics. The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics. The differences in sensitivity between the two groups were not significantly different (p less than 0.05). We conclude that antibiotic therapy does not affect the sensitivity of the /sup 111/In-labeled leukocyte scan.

  7. 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.

  8. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer - 90Y conjugates in treatment of prostate tumors

    PubMed Central

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction The treatment of prostate cancer using a radiotherapeutic 90Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA)copolymer can be enhanced with localized tumor hyperthermia. An 111In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90Y HPMA copolymer with hyperthermia. Methods HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111In for imaging or 90Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors. PMID:24461626

  9. 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.

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

    PubMed

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

    2014-04-01

    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.

  11. 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

  12. 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.

  13. The processing and fate of antibodies and their radiolabels bound to the surface of tumor cells in vitro: A comparison of nine radiolabels

    SciTech Connect

    Shih, L.B.; Thorpe, S.R.; Griffiths, G.L.; Diril, H.; Ong, G.L.; Hansen, H.J.; Goldenberg, D.M.; Mattes, M.J.

    1994-05-01

    Processing radiolabeled degradation products is the key factor affecting retention of antibodies within the cell. In this study, the authors have analyzed the processing of antibodies labeled in nine different ways. Antibodies were labeled with three different radioisotopes and seven different forms of {sup 125}I. Eight of the radiolabels (except {sup 188}Re) were conjugated to the same antibody, MA103, and tested on the renal carcinoma cell line SK-RC-18 and/or the ovarian carcinoma cell line SK-OV-6. Rhenium conjugation utilized the antibody RS7, the target cell line ME180 and three of the other radiolabels were also tested with this antibody-target cell combination for comparison. Iodine conjugated to antibodies by conventional methods was rapidly released from the cell after antibody catabolism. In contrast, iodinated moieties, such as dilactitol-tyramine and inulin-tyramine were retained within cells four to five times longer. The use of radiolabels that are trapped within cells after antibody catabolism can potentially increase the dose of radiation delivered to the tumor, from the same amount of radioactivity deposited by a factor of four or five. The prolonged retention of {sup 111}In relative to {sup 125}I is not due to deiodination of iodine conjugates, but rather to intracellular retention of catabolic products containing {sup 111}In, perhaps within lysosomes. 45 refs., 4 figs., 1 tab.

  14. Dose rate measurements from radiopharmaceuticals: implications for nuclear medicine staff and for children with radioactive parents.

    PubMed

    Greaves, C D; Tindale, W B

    1999-02-01

    Following the introduction of a number of radiopharmaceuticals, we assessed the dose received by staff working in the nuclear medicine department and also by children who may be in close contact with a radioactive parent. We measured departure dose rates (microSv.h-1) at distances of 0.1, 0.5 and 1.0 m from the skin surface at the level of the thyroid, chest and bladder of patients undergoing the following nuclear medicine procedures: MUGA scans using 99Tcm-labelled red blood cells, myocardial perfusion scans using 99Tcm-labelled radiopharmaceuticals, lymphoscintigraphy using colloidal 99Tcm (Re) sulphide, bone scans using 99Tcm-labelled oxidronate, 111In-octreotide scans, 111In-labelled leukocyte studies and cardiac reinjection studies using 201Tl. The maximum dose rates at 0.1 m were those from MUGA studies (167.3 microSv.h-1) and myocardial perfusion studies (one-day protocol = 391.7 microSv.h-1, two-day protocol = 121.8 microSv.h-1). The implications of these dose rates on both technical and nursing staff are assessed. Also, the dose received by an infant in close contact with a parent following a nuclear medicine investigation was estimated.

  15. 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.

  16. 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.

  17. A Case of Focal Bone Marrow Reconversion Mimicking Bone Metastasis: The Value of 111Indium Chloride.

    PubMed

    Tanaka, Takashi; Gobara, Hideo; Inai, Ryota; Iguchi, Toshihiro; Tada, Akihiro; Sato, Shuhei; Yanai, Hiroyuki; Kanazawa, Susumu

    2016-08-01

    We present a case of a 66-year-old man with esophageal carcinoma. 18Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for evaluating distant metastasis and staging revealed 18F-FDG uptake in the third lumbar vertebra and other vertebrae. Magnetic resonance imaging could not differentiate bone metastases from benign bone lesions. We considered the possibility of bone marrow reconversion. 111Indium chloride (111In-Cl3) scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) revealed erythroid bone marrow components in the bone lesions. The diagnosis of bone marrow reconversion was pathologically confirmed by a bone biopsy of the third lumbar vertebra. The patient underwent esophagectomy and has remained disease-free in the 2 years since. To the best of our knowledge, this is the first report to describe the usefulness of 111In-Cl3 with SPECT/CT for the diagnosis of bone marrow reconversion. PMID:27549674

  18. Radioimmunodetection of cancer with the use of indium-111-labeled monoclonal antibodies.

    PubMed

    Dillman, R O; Beauregard, J; Ryan, K P; Hagan, P L; Clutter, M; Amox, D; Frincke, J M; Bartholomew, R M; Burnett, K G; David, G S

    1987-01-01

    We have infused 13 111In-labeled murine IgG monoclonal antibodies (MAb) into 73 patients who had been diagnosed as having 7 types of cancers, and 3 111In-labeled human MAb into 8 patients with breast cancer. To each patient, 1.5-5 mCi attached to a maximum of 1 mg MAb had been given in a total MAb dose of 0.5-500 mg. The most encouraging overall results have been obtained with anti-human T-cell MAb T101 (33 of 33 tumor sites imaged in 5 patients), antimelanoma MAb P96.5 (47 of 88 sites imaged in 21 patients), anti-prostate MAb PSA399 (14 of 21 sites imaged in 4 patients), and anti-colon MAb ZCE025 (16 of 26 sites imaged in 12 patients). Poor imaging results were related to lower doses, reactivity with circulating cells, and limited antigen expression in various tumor sites. The problems involved in radioimmunodetection included low extraction of MAb from the serum by the tumor that resulted in poor tumor uptake of the radiopharmaceutical, and high background activity in the liver, heart, spleen, and gastrointestinal tract that made imaging difficult in those areas. Heterogeneous antigen production leaves some tumor deposits without targets, and the immunogenicity of the MAb limits use of these agents repetitively in humans. Nevertheless, these early results are encouraging for their potential diagnostic and therapeutic applications.

  19. Indium 111 ZCE-025 immunoscintigraphy in occult recurrent colorectal cancer with elevated carcinoembryonic antigen level

    SciTech Connect

    Doerr, R.J.; Abdel-Nabi, H.; Merchant, B. )

    1990-02-01

    We investigated the utility of scanning with indium 111 labeled to monoclonal antibody in 13 patients after curative resection of colorectal cancer who had elevated carcinoembryonic antigen levels and negative results of clinical workup. Each patient received 1 mg of anti-carcinoembryonic antigen monoclonal antibody type ZCE 025 labeled with 5.5 mCi of {sup 111}In, plus 9 to 39 mg of the same antibody unlabeled. Patients underwent scanning 3 to 7 days after infusion by planar and emission computed tomography. ZCE-025 monoclonal antibody imaging detected tumor recurrence or metastasis in 11 of 13 patients. In one patient the monoclonal antibody scan gave a true-negative result, and in one patient the monoclonal antibody scan failed to disclose a metachronous cecal primary. Tumor sites identified were the pelvis (2 patients), abdominal wall (2), retroperitoneum (1), lymph nodes (3); liver (2), bone (2), and lung (1). The accurate localization of colorectal carcinoma recurrences by means of {sup 111}In ZCE-025 monoclonal antibody demonstrates the usefulness of this diagnostic agent in the setting of elevated carcinoembryonic antigen level and negative results of clinical and radiologic workup.

  20. Myocardial neutrophil accumulation during reperfusion after reversible or ischemic injury

    SciTech Connect

    Go, L.O.; Murry, C.E.; Richard, V.J.; Weischedel, G.R.; Jennings, R.B.; Reimer, K.A. )

    1988-11-01

    Recent studies suggest that polymorphonuclear leukocytes (PMNs) may cause additional myocyte injury during reperfusion of ischemic myocardium. The present study was done to investigate whether PMNs accumulate in myocardium during early reperfusion after reversible or irreversible ischemic injury. Open-chest anesthetized dogs underwent circumflex coronary occlusions for 12 min, 40 min, or 90 min, followed by 1 h of reperfusion. Autologous PMNs were radiolabeled with {sup 111}In and reinjected to quantitate myocardial PMN influx during reflow. {sup 125}I-labeled albumin was injected simultaneously to correct for {sup 111}In associated with plasma proteins in myocardial tissue. The number of PMNs was determined in the inner, middle, and outer one-third of nonischemic and ischemic-reperfused myocardium. In the 12-min group, 40% fewer PMNs were present in the reperfused than in the nonischemic control tissue. In contrast, in both the 40- and 90-min groups, PMN accumulation was two- to six-fold greater in the ischemic-reperfused than nonischemic myocardium, with a transmural gradient of PMN influx increasing from the outer to inner layers. Collateral blood flow, measured with radioactive microspheres, was not significantly different among the three groups. The failure of PMNs to accumulate during reperfusion after 12 min of ischemia does not support the hypothesis that PMNs contribute to postischemic dysfunction of reversibly injured myocytes. Whether PMNs cause cell death during early reperfusion after longer ischemic episodes remains unknown; however, the rapidity of PMN accumulation in the zones of predicted infarction is consistent with this possibility.

  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. 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.

  3. Thermal stability of nonmagnetic Cd and In impurities in Fe3O4

    NASA Astrophysics Data System (ADS)

    Sato, W.; Ida, T.; Komatsuda, S.; Fujisawa, T.; Takenaka, S.; Ohkubo, Y.

    2016-10-01

    Magnetite (Fe3O4) was doped with radioactive 111mCd and 111In ions as impurities, and their residence sites and thermal stability were investigated by means of time-differential perturbed angular correlation (TDPAC) spectroscopy. Well-defined TDPAC spectra unequivocally show their sites: Cd ions are stably located only in the tetrahedral A site in all the temperature range of the present observation (77 K-873 K); In ions also specifically occupy the A site at low temperature, but at high temperature part of them select the B site in a reversible fashion. The energy difference between the A and B sites for the accommodation of In was experimentally determined to be 0.119 (9) eV by assuming a Boltzmann distribution for the populations of the 111In probe in the respective sites. The element-dependent thermal stabilities observed for Cd and In were well corroborated by density functional theory calculations. The successful observation of thermally activated site-to-site displacement of impurity In ions in Fe3O4 is reported.

  4. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R. . Dept. of Physics); Evenson, W.E. . Dept. of Physics and Astronomy); Rasera, R.L. . Dept. of Physics); Sommers, J.A. )

    1991-01-01

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  5. PAC spectroscopy of electronic ceramics

    SciTech Connect

    Gardner, J.A.; Wang, Ruiping; Schwenker, R.; Evenson, W.E.; Rasera, R.L.; Sommers, J.A.

    1991-12-31

    Dilute indium dopants in cerium oxides and YBa{sub 2}Cu{sub 3}O{sub x} have been studied by{sup 111}In/Cd Perturbed Angular Correlation (PAC) spectroscopy. By controlling oxygen vacancy concentration in the cerium oxides through doping or high-temperature vacuum annealing, we have found that indium always forms a defect complex unless the sample is doped to reduce greatly the oxygen vacancy concentration. Three different vacancy-associated complexes are found with concentrations that depend on doping and oxygen stoichiometry. Another defect complex occurs in samples having negligible vacancy concentration. At low temperatures, evidence is found of interaction with an electronic hole trapped by {sup 111}Cd after the radioactive decay of the {sup 111}In parent. In YBa{sub 2}Cu{sub 3}O{sub x} the indium substitutes preferentially at the Y site but has measurable probability of substitution in at least one of the two copper sites. A symmetry change near 650 {degree}C is consistent with the well-documented orthorhombic/tetragonal transition for samples in air or oxygen.

  6. The SPECT imaging shows the accumulation of neural progenitor cells into internal organs after systemic administration in middle cerebral artery occlusion rats.

    PubMed

    Lappalainen, Riikka S; Narkilahti, Susanna; Huhtala, Tuulia; Liimatainen, Timo; Suuronen, Tiina; Närvänen, Ale; Suuronen, Riitta; Hovatta, Outi; Jolkkonen, Jukka

    2008-08-01

    The regenerative potential of stem cells from various sources has been under intense investigation in the experimental models of cerebral ischemia. To end up with a restorative therapeutic treatment, it is crucial to get the cell transplants to the site of injury. Here, we evaluated the feasibility of small animal SPECT/CT in assessing the definite accumulation of (111)In-oxine-labeled human embryonic stem (ES) cell-derived neural progenitors and rat hippocampal progenitors after intravenous or intra-arterial administration (femoral vein vs. common carotid artery) in middle cerebral artery occlusion (MCAO) and sham-operated rats. Cell detection was carried out immediately and 24h after the infusion using a SPECT/CT device. The results showed that after intravenous injections both cell types accumulated primarily into internal organs, instead of brain. In contrast, after intra-arterial injection, a weak signal was detected in the ischemic hemisphere. Additional studies showed that the detection sensitivity of SPECT/CT device was approximately 1000 (111)In-oxine-labeled cells and labeling did not affect the cell viability. In conclusion, a small animal SPECT is powerful technique to study the whole body biodistribution of cell-based therapies. Our data showed that intravenous administration is not an optimal route to deliver neural progenitor cell-containing transplants into the brain after MCAO in rats. PMID:18572314

  7. 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.

  8. The white blood cell scan in orthopedics

    SciTech Connect

    Propst-Proctor, S.L.; Dillingham, M.F.; McDougall, I.R.; Goodwin, D.

    1982-08-01

    A new nuclear scanning technique was found more specific for bone, joint, and soft tissue infections than any previously described scanning technique. The leukocyte scan, whereby a patient's own cells are labeled with a radioactive tagging agent (/sup 111/In oxine), can distinguish an active infectious process from other pain-inducing conditions. Ninety-seven /sup 111/In labeled autologous leukocyte scans were performed in 88 patients. The findings in 17 of 40 patients scanned for possible acute osteomyelitis, six of nine for suspected septic arthritis, and six for possible soft tissue infections, were positive. Subsequent clinical courses verified the infectious nature of these processes in all patients. Patients who had chronic osteomyelitis (14), bony metastases (four patients), heterotopic ossification (three), and degenerative arthritis (two) demonstrated negative findings. Of the seven patients scanned for acute long-bone fractures, one demonstrated positive findings. Nine scans demonstrated positive findings without determined causes. The leukocyte scan is a useful addition to the diagnostic tools of the orthopedic surgeon.

  9. 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.

  10. 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.

  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. Assessment of sites of marrow and extramedullary hematopoiesis by hybrid imaging in primary myelofibrosis patients.

    PubMed

    Ojeda-Uribe, Mario; Morel, Olivier; Ungureanu, Constantin; Desterke, Christophe; Le Bousse-Kerdilès, Marie-Caroline; Boulahdour, Hatem

    2016-09-01

    We investigated noninvasive procedures by hybrid imaging to assess the sites of active or inactive hematopoiesis in patients with primary myelofibrosis (PMF). To this end, we used two radionuclides, technetium 99m ((99m) Tc) and indium 111-chloride ((111) In-Cl3 ), coupled with single-photon emission tomography/computed tomography (SPECT/CT). We studied five patients with PMF and one with secondary myelofibrosis (MF). The classical pattern of lower fixation of both tracers at the axial skeleton where the myelofibrotic process occurs and the reactivation of sites of active hematopoiesis at the distal skeleton were confirmed. Coupling both radionuclides to SPECT/CT imaging allowed for more precise visualization of the sites of extramedullary hematopoiesis as those observed in the spleen and liver. Splenic high uptake of (111) In-Cl3 coupled with SPECT/CT represents a pathognomonic feature of PMF. We conclude that, the hybrid imaging procedures that we studied might constitute an alternative noninvasive method for the screening of the whole-body marrow and, by this way, to assess the impact of targeted therapies in PMF patients in whom it is well known that the distribution of the hematopoietic active areas is disturbed. Hybrid imaging could also be useful for diagnostic purposes in cases of early PMF or in suspected cases of myelofibrosis secondary to polycythemia vera or essential thrombocythemia. PMID:27518041

  13. Intracavitary use of two radiolabeled tumor-associated monoclonal antibodies

    SciTech Connect

    Malamitsi, J.; Skarlos, D.; Fotiou, S.; Papakostas, P.; Aravantinos, G.; Vassilarou, D.; Taylor-Papadimitriou, J.; Koutoulidis, K.; Hooker, G.; Snook, D.

    1988-12-01

    Six patients with metastatic breast cancer and malignant pleural effusions and 13 patients with known or suspected ovarian cancer, underwent immunoscintigraphy after intracavitary (intrapleural or intraperitoneal) administration of iodine-131-(131I) or indium-111-(111In) labeled tumor associated monoclonal antibodies HMFG2 and H17E2. This method proved to be sensitive and specific with a true-positive result in 13 out of 14 patients with tumor and a true-negative result in five out of five patients without tumor. At any one time, 65%-80% of the whole-body radioactivity was closely associated with the cavity into which the radiolabeled antibody was administered while the radioactivity in the blood was always low, (approximately 4 X 10(-3) of administered dose/ml of blood). Concentrations of radiolabeled antibody (per gram of tumor tissue) ranged from 0.02%-0.1% of the injected dose in intracavitary tumors, but only 0.002% in a retroperitoneal metastasis. The specificity of this approach was documented in four control patients with benign ovarian cysts and in two patients who were imaged using both specific and nonspecific radiolabeled antibody. We conclude that the intracavitary administration of 131I- or 111In-labeled HMFG2 and H17E2 is a favorable route of administration and offers significant advantages over previously reported intravenous administration for the localization of breast or ovarian metastases confined to the pleural or peritoneal cavities.

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

    NASA Astrophysics Data System (ADS)

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-01

    We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

  15. Electric field gradient in nanostructured SnO2 studied by means of PAC spectroscopy using 111Cd or 181Ta as probe nuclei

    NASA Astrophysics Data System (ADS)

    Ramos, Juliana Marques; Martucci, Thiago; Carbonari, Artur Wilson; de Souza Costa, Messias; Saxena, Rajendra Narain; Vianden, Reiner

    2013-05-01

    Electric quadrupole interactions were studied in pure and Mn-doped powder samples and thin films of SnO2 using perturbed γγ angular correlation spectroscopy (PAC). The powder samples were prepared by Sol gel method and the thin film were prepared on the Si (100) substrate by sputtering technique using Sn in the oxygen atmosphere. The samples were characterized by x-ray diffraction, energy dispersive spectroscopy and scanning electron microscopy. The thickness of the film was 100 nm. The average particle size of the SnO2 powder samples was determined to be smaller than 60 nm. The radioactive 111In and 181Hf tracers were introduced in the powder samples during the sol gel chemical process. Radioactive 111In was implanted on the SnO2 thin films using the University of Bonn ion implanter (BONIS). PAC measurements were carried out in a four BaF2 detector spectrometer in the temperature range of 77-973 K for samples annealed at different temperatures. The PAC results for both nuclear probes show the presence of two electric quadrupole interactions. The major fractions in both cases correspond to the substitutional sites in the rutile phase of SnO2. The results are compared with previous PAC measurements.

  16. 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.

  17. 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

  18. 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.

  19. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    SciTech Connect

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. )

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  20. 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.

  1. 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.

  2. Intracavitary use of two radiolabeled tumor-associated monoclonal antibodies.

    PubMed

    Malamitsi, J; Skarlos, D; Fotiou, S; Papakostas, P; Aravantinos, G; Vassilarou, D; Taylor-Papadimitriou, J; Koutoulidis, K; Hooker, G; Snook, D

    1988-12-01

    Six patients with metastatic breast cancer and malignant pleural effusions and 13 patients with known or suspected ovarian cancer, underwent immunoscintigraphy after intracavitary (intrapleural or intraperitoneal) administration of iodine-131-(131I) or indium-111-(111In) labeled tumor associated monoclonal antibodies HMFG2 and H17E2. This method proved to be sensitive and specific with a true-positive result in 13 out of 14 patients with tumor and a true-negative result in five out of five patients without tumor. At any one time, 65%-80% of the whole-body radioactivity was closely associated with the cavity into which the radiolabeled antibody was administered while the radioactivity in the blood was always low, (approximately 4 X 10(-3) of administered dose/ml of blood). Concentrations of radiolabeled antibody (per gram of tumor tissue) ranged from 0.02%-0.1% of the injected dose in intracavitary tumors, but only 0.002% in a retroperitoneal metastasis. The specificity of this approach was documented in four control patients with benign ovarian cysts and in two patients who were imaged using both specific and nonspecific radiolabeled antibody. We conclude that the intracavitary administration of 131I- or 111In-labeled HMFG2 and H17E2 is a favorable route of administration and offers significant advantages over previously reported intravenous administration for the localization of breast or ovarian metastases confined to the pleural or peritoneal cavities.

  3. In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

    PubMed

    Pittet, Mikael J; Grimm, Jan; Berger, Cedric R; Tamura, Takahiko; Wojtkiewicz, Gregory; Nahrendorf, Matthias; Romero, Pedro; Swirski, Filip K; Weissleder, Ralph

    2007-07-24

    Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies. PMID:17640914

  4. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

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

    PubMed

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

    1993-02-01

    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.

  6. DNA double-strand break repair: a theoretical framework and its application.

    PubMed

    Murray, Philip J; Cornelissen, Bart; Vallis, Katherine A; Chapman, S Jon

    2016-01-01

    DNA double-strand breaks (DSBs) are formed as a result of genotoxic insults, such as exogenous ionizing radiation, and are among the most serious types of DNA damage. One of the earliest molecular responses following DSB formation is the phosphorylation of the histone H2AX, giving rise to γH2AX. Many copies of γH2AX are generated at DSBs and can be detected in vitro as foci using well-established immuno-histochemical methods. It has previously been shown that anti-γH2AX antibodies, modified by the addition of the cell-penetrating peptide TAT and a fluorescent or radionuclide label, can be used to visualize and quantify DSBs in vivo. Moreover, when labelled with a high amount of the short-range, Auger electron-emitting radioisotope, (111)In, the amount of DNA damage within a cell can be increased, leading to cell death. In this report, we develop a mathematical model that describes how molecular processes at individual sites of DNA damage give rise to quantifiable foci. Equations that describe stochastic mean behaviours at individual DSB sites are derived and parametrized using population-scale, time-series measurements from two different cancer cell lines. The model is used to examine two case studies in which the introduction of an antibody (anti-γH2AX-TAT) that targets a key component in the DSB repair pathway influences system behaviour. We investigate: (i) how the interaction between anti-γH2AX-TAT and γH2AX effects the kinetics of H2AX phosphorylation and DSB repair and (ii) model behaviour when the anti-γH2AX antibody is labelled with Auger electron-emitting (111)In and can thus instigate additional DNA damage. This work supports the conclusion that DSB kinetics are largely unaffected by the introduction of the anti-γH2AX antibody, a result that has been validated experimentally, and hence the hypothesis that the use of anti-γH2AX antibody to quantify DSBs does not violate the image tracer principle. Moreover, it provides a novel model of DNA damage

  7. 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

  8. 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

  9. Structural Characterization and in Vivo Evaluation of β-Hairpin Peptidomimetics as Specific CXCR4 Imaging Agents

    PubMed Central

    Lesniak, Wojciech G.; Sikorska, Emilia; Shallal, Hassan; Azad, Babak Behnam; Lisok, Ala; Pullambhatla, Mrudula; Pomper, Martin G.; Nimmagadda, Sridhar

    2015-01-01

    The CXCR4 chemokine receptor is integral to several biological functions and plays a pivotal role in the pathophysiology of many diseases. As such, CXCR4 is an enticing target for the development of imaging and therapeutic agents. Here we report the evaluation of the POL3026 peptidomimetic template for the development of imaging agents that target CXCR4. Structural and conformational analyses of POL3026 and two of its conjugates, DOTA (POL-D) and PEG12-DOTA (POL-PD), by circular dichroism, two-dimensional NMR spectroscopy and molecular dynamics calculations are reported. In silico observations were experimentally verified with in vitro affinity assays and rationalized using crystal structure-based molecular modeling studies. [111In]-labeled DOTA conjugates were assessed in vivo for target specificity in CXCR4 expressing subcutaneous U87 tumors (U87-stb-CXCR4) through single photon emission computed tomography (SPECT/CT) imaging and biodistribution studies. In silico and in vitro studies show that POL3026 and its conjugates demonstrate similar interactions with different micelles that mimic cellular membrane and that the ε-NH2 of lysine7 is critical to maintain high affinity to CXCR4. Modification of this group with DOTA or PEG12-DOTA led to the decrease of IC50 value from 0.087 nM for POL3026 to 0.47 nM and 1.42 nM for POL-D and POL-PD, respectively. In spite of the decreased affinity toward CXCR4, [111In]POL-D and [111In]POL-PD demonstrated high and significant uptake in U87-stb-CXCR4 tumors compared to the control U87 tumors at 90 min and 24 h post injection. Uptake in U87-stb-CXCR4 tumors could be blocked by unlabeled POL3026, indicating specificity of the agents in vivo. These results suggest POL3026 as a promising template to develop new imaging agents that target CXCR4. PMID:25590535

  10. 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

  11. DNA double-strand break repair: a theoretical framework and its application

    PubMed Central

    Cornelissen, Bart; Vallis, Katherine A.; Chapman, S. Jon

    2016-01-01

    DNA double-strand breaks (DSBs) are formed as a result of genotoxic insults, such as exogenous ionizing radiation, and are among the most serious types of DNA damage. One of the earliest molecular responses following DSB formation is the phosphorylation of the histone H2AX, giving rise to γH2AX. Many copies of γH2AX are generated at DSBs and can be detected in vitro as foci using well-established immuno-histochemical methods. It has previously been shown that anti-γH2AX antibodies, modified by the addition of the cell-penetrating peptide TAT and a fluorescent or radionuclide label, can be used to visualize and quantify DSBs in vivo. Moreover, when labelled with a high amount of the short-range, Auger electron-emitting radioisotope, 111In, the amount of DNA damage within a cell can be increased, leading to cell death. In this report, we develop a mathematical model that describes how molecular processes at individual sites of DNA damage give rise to quantifiable foci. Equations that describe stochastic mean behaviours at individual DSB sites are derived and parametrized using population-scale, time-series measurements from two different cancer cell lines. The model is used to examine two case studies in which the introduction of an antibody (anti-γH2AX-TAT) that targets a key component in the DSB repair pathway influences system behaviour. We investigate: (i) how the interaction between anti-γH2AX-TAT and γH2AX effects the kinetics of H2AX phosphorylation and DSB repair and (ii) model behaviour when the anti-γH2AX antibody is labelled with Auger electron-emitting 111In and can thus instigate additional DNA damage. This work supports the conclusion that DSB kinetics are largely unaffected by the introduction of the anti-γH2AX antibody, a result that has been validated experimentally, and hence the hypothesis that the use of anti-γH2AX antibody to quantify DSBs does not violate the image tracer principle. Moreover, it provides a novel model of DNA damage

  12. 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. PMID:27544265

  13. 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

  14. Detection of acute synthetic vascular graft infection with In-labeled leukocyte scanning: an animal study

    SciTech Connect

    Dries, D.J.; Alazraki, N.; Lawrence, P.F.; Murphy, K.M.; Kercher, J.; Datz, F.L.; Christian, P.; Taylor, A. Jr.

    1985-11-01

    Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Indium- -labeled leukocyte imaging holds promise as a diagnostic tool to identify vascular graft infection, but reported data on its accuracy are somewhat sparse and conflicting. In this study, 13 mongrel dogs received Dacron aortic interposition grafts. Seven grafts were contaminated at the time of surgery by topical ATCC Staphylococcus aureus concentrated at 10(8) organisms/ml. Six control animals received no graft contamination. All infected animals were sacrificed on the second postoperative day after In leukocyte scanning. The results showed a sensitivity of 71%, specificity of 100%, and accuracy of 85% for the 111In leukocyte study in detecting early graft infections; false-positive leukocyte scans in the early postoperative period were not a problem as has been reported by others. These data indicate that leukocyte scanning for graft infection detection is likely to be clinically valuable.

  15. 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.

  16. Alternative Single-Solvent Electrolytes Based on Cyanoesters for Safer Lithium-Ion Batteries.

    PubMed

    Brox, Sebastian; Röser, Stephan; Husch, Tamara; Hildebrand, Stephan; Fromm, Olga; Korth, Martin; Winter, Martin; Cekic-Laskovic, Isidora

    2016-07-01

    To identify alternative single-solvent-based electrolytes for application in lithium-ion batteries (LIBs), adequate computational methods were applied to screen specified physicochemical and electrochemical properties of new cyanoester-based compounds. Out of 2747 possible target compounds, two promising candidates and two structurally equivalent components were chosen. A constructive selection process including evaluation of basic physicochemical properties as well assessing the compatibility towards graphitic anodes was initiated to identify the most promising candidates. With addition of a film-forming additive in a low concentration, the most promising candidate showed an adequate long-term cycling stability with LiNi1/3 Mn1/3 Co1/3 O2 [NMC(111)] in a full-cell setup using graphite as anode material. The main advantages of the new electrolyte formulation are related to its good thermal behavior, especially with regard to safety in combination with satisfying electrochemical performance.

  17. 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.

  18. Hybridization of impurity states with the Shockley surface band versus bulk states

    NASA Astrophysics Data System (ADS)

    Barral, María Andrea; Llois, Ana María; Aligia, Armando A.

    2004-07-01

    The characteristics of the Shockley surface states on Cu(111) in the presence of Co impurity adsorbates are studied by means of one electron calculation performed using a well parametrized Hamiltonian in a local basis. Local densities of states in the spillover region as well as the relative hybridization strengths of Co “ d ” orbitals with bulk and surface states are obtained. We show that Co 3d orbitals hybridize mostly with Cu bulk conduction states, thus giving ground to recent experimental results [N. Knorr, M. A. Schneider, L. Diekhoner, P. Wahl, and K. Kern, Phys. Rev. Lett. 88, 096804 (2002)] in the sense that the observed Kondo resonances are being dominated by Cu bulk electrons.

  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. 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

    2015-11-01

    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.

  1. 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.

  2. 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

    2015-04-01

    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%).

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Biomedical probe using a fiber-optic coupled scintillator.

    PubMed

    Swinth, K L; Ewins, J H

    1976-01-01

    A high-sensitivity biomedical radiation probe which employs a fiber-optic coupled NaI(Tl) scintillator as a detector is described. It was developed for in vivo counting of low-energy 239Pu photons from material located in the tracheobronchial lymph nodes.-This probe is 20 times as sensitive as a solid-state probe (avalanche diode) previously developed for this application. Tests with 99mTc show a sensitivity more than 90 times greater than biomedical probes using DcTe of GaAs; however, the improved sensitivity is largely due to an increased sensitive volume. Probes were evaluated in animals and phantoms for detection of 239Pu and for location of lung tumors labeled with 111In. PMID:1264039

  8. Potential oscillations and S-shaped polarization curve in the continuous electro-oxidation of CO on platinum single-crystal electrodes

    SciTech Connect

    Koper, Marc T.M.; Schmidt, Thomas J.; Markovic, Nenad M.; Ross, Philip N.

    2001-03-01

    The occurrence of an S-shaped polarization curve in a simple model for the continuous electrochemical oxidation of CO on a platinum electrode is discussed. In the model, the S-shaped polarization curve is caused by the competitive Langmuir-Hinshelwood mechanism between surface-bonded CO and OH. The reaction is studied experimentally on single-crystal platinum rotating disk electrodes in perchloric and sulfuric acid solution, and it is shown that the voltammetry is in good agreement with the model predictions. When studied under current-controlled conditions, a fast galvanodynamic scan indeed suggests the existence of the S-shaped polarization curve. At lower scan rates, however, irregularities and small-amplitude irregular fluctuations or oscillations in potential are observed. Very regular potential oscillations under current-controlled conditions are observed only on Pt(111) in sulfuric acid. The possible origin of these irregularities and oscillations is discussed in relation to the existing theories of electrochemical instabilities.

  9. 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.

  10. In situ infrared study on the effect of pH on anion adsorption at Pt(111) electrodes from acid sulfate solutions

    SciTech Connect

    Faguy, P.W.; Marinkovic, N.S.; Adzic, R.R.

    1996-01-24

    From the in situ FTIR spectroscopy of the electrode/electrolyte solution interface at pH values of 1.2, 2.0 and 3.4, it can be confirmed that the adsorbate associated with the anomalous peaks in the cyclic voltammetry of Pt(111) in sulfate- and bisulfate-containing solutions is not the sulfate anion. The structure of the bisulfate-like adsorbate is tentatively postulated to be a sulfate ion/hydronium ion ion pair: SO{sub 4}{sup 2-}xH{sub 3}O{sup +}. Over the potentials in question, and only in solutions with appreciable HSO{sub 4}{sup -} concentration, can IR bands be found that are associated with the adsorbed species. 36 refs., 4 figs., 1 tab.

  11. 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

  12. New derivatives of vitamin B12 show preferential targeting of tumors.

    PubMed

    Waibel, Robert; Treichler, Hansjörg; Schaefer, Niklaus G; van Staveren, Dave R; Mundwiler, Stefan; Kunze, Susanne; Küenzi, Martin; Alberto, Roger; Nüesch, Jakob; Knuth, Alexander; Moch, Holger; Schibli, Roger; Schubiger, Pius August

    2008-04-15

    Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled ((57)Co and (111)In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue. By abolishing the interaction of a tailored vitamin B12 derivative to its transport protein transcobalamin II and therefore interrupting transcobalamin II receptor and megalin mediated uptake in normal tissue, preferential accumulation of a radiolabeled vitamin in cancer tissue could be accomplished. We identified transcobalamin I on tumors as a possible new receptor for this preferential accumulation of vitamin-mediated targeting. The low systemic distribution of radioactivity and the high tumor to blood ratio opens the possibility of a more successful clinical application of vitamin B12 for imaging or therapy.

  13. Kinetic characterization of Channa striatus muscle sarcoplasmic and myofibrillar protein hydrolysates.

    PubMed

    Ghassem, Masomeh; Fern, See Siau; Said, Mamot; Ali, Zainon Mohd; Ibrahim, Saadiah; Babji, Abdul Salam

    2014-03-01

    This study was conducted to evaluate the kinetic characteristics of proteolytic activity of proteases on Channa striatus protein fractions. Degree of hydrolysis (DH), amino acid composition and kinetic parameters of sarcoplasmic and myofibrillar proteins were investigated when incubated with proteinase K and thermolysin, separately. After 30 min incubation with proteases, a decrease in DH of sarcoplasmic protein was observed whereas, hydrolysis of myofibrillar protein with proteases took 2 h with an increase in DH. The major amino acids were glutamic acid (16.6%) in thermolysin- myofibrillar hydrolysate followed by aspartic acid (11.1%) in sarcoplasmic protein fraction with no enzyme treatment and lysine (10%) in thermolysin-myofibrillar hydrolysate. The apparent Michaelis constant of proteinase K was lower than thermolysin for both sarcoplasmic and myofibrillar proteins. However, rate of turnover and enzyme efficiency suggested that sarcoplasmic and myofibrillar proteins are suitable substrates for proteinase K and thermolysin hydrolytic reaction, respectively.

  14. 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

  15. 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.

  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.

    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.

  18. Hyperfine fields at the (001) Fe/Ag interface.

    NASA Astrophysics Data System (ADS)

    Rodriguez, C. O.; Peltzer Y Blanca, E. L.; Ganduglia-Pirovano, M. V.; Petersen, M.

    2000-03-01

    First principles studies within local spin density functional theory have been performed to calculate and investigate the microscopic origin of Hyperfine Fields (HFF's) of a Cd impurity in bulk Fe and at the (001) interface of Fe/Ag. Monolayer resolved HFF's at this interface have recently been studied using ^111In/^111Cd probe atoms in PAC ( B.U.Runge, M.Dippel, G.Fillebock, K. Jacobs, U. Kohl and G. Schatz, Phys. Rev. Lett. 79), 3054 (1997) determinations. The reduction of the symmetry and the changes in the chemical environment of Cd at each side of the interface as compared to Cd in Fe bulk can be linked to the interpretation of the HFF's.

  19. PEG-Like Nanoprobes: Multimodal, Pharmacokinetically and Optically Tunable Nanomaterials

    PubMed Central

    Guo, Yanyan; Yuan, Hushan; Claudio, Natalie M.; Kura, Sreekanth; Shakerdge, Naomi; Mempel, Thorsten R.; Bacskai, Brian J.; Josephson, Lee

    2014-01-01

    “PEG-like Nanoprobes” (PN’s) are pharmacokinetically and optically tunable nanomaterials whose disposition in biological systems can be determined by fluorescence or radioactivity. PN’s feature a unique design where a single PEG polymer surrounds a short fluorochrome and radiometal bearing peptide, and endows the resulting nanoprobe with pharmacokinetic control (based on molecular weight of the PEG selected) and optical tunability (based on the fluorochrome selected), while the chelate provides a radiolabeling option. PN’s were used to image brain capillary angiography (intravital 2-photon microscopy), tumor capillary permeability (intravital fluorescent microscopy), and the tumor enhanced permeability and retention (EPR) effect (111In-PN and SPECT). Clinical applications of PN’s include use as long blood half-life fluorochromes for intraoperative angiography, for measurements of capillary permeability in breast cancer lesions, and to image EPR by SPECT, for stratifying patient candidates for long-circulating nanomedicines that may utilize the EPR mechanism. PMID:24781778

  20. 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.

  1. [Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].

    PubMed

    Ostrovskaia, R U; Liapina, L A; Pastorova, V E; Mirzoev, T Kh; Gudasheva, T A; Seredenin, S B; Ashmarin, I P

    2002-01-01

    The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug. PMID:12109290

  2. 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.

  3. In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen.

    PubMed

    Smith-Jones, P M; Vallabahajosula, S; Goldsmith, S J; Navarro, V; Hunter, C J; Bastidas, D; Bander, N H

    2000-09-15

    Prostate-specific membrane antigen (PSMA) is a well-characterized cell surface antigen expressed by virtually all prostate cancers (PCas). PSMA has been successfully targeted in vivo with (111)In-labeled 7E11 monoclonal antibody (mAb; ProstaScint; Cytogen, Princeton, NJ), which binds to an intracellular epitope of PSMA. This work reports the in vitro characterization of three recently developed mAbs that bind the extracellular domain of PSMA (PSMAext). Murine mAbs J415, J533, J591, and 7E11 were radiolabeled with 131I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid labeled with (111)In. The uptake and cellular processing of these antibodies were evaluated in viable LNCaP cells. All four mAbs could be labeled with 131I up to a specific activity of 350 MBq/mg with no or little apparent loss of immunoreactivity. Competition assays revealed that J415 and J591 compete for binding to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. mAb 7E11 did not inhibit the binding of J415, J533, or J591 (or vice versa), consistent with earlier work that these latter mAbs bind PSMAext whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affinity (Kds 1.76 and 1.83 nM), whereas J533 had a lower affinity (Kd, 18 nM). In parallel studies, all four mAbs bound to a similar number of PSMA sites expressed by permeabilized cells (1,000,000-1,300,000 sites/cell). In parallel studies performed with viable LNCaP cells, J415, J533, and J591 bound to a similar number of PSMA sites (i.e., 600,000-800,000 sites/cell), whereas 7E11 bound only to a subpopulation of the available PSMA sites (95,000 sites/cell). This apparent binding of 7E11 to viable cells can be accounted for by a 5

  4. Short communication: Isolation of Shiga toxin-producing Escherichia coli in raw milk and mozzarella cheese in southern Italy.

    PubMed

    Nobili, G; Franconieri, I; Basanisi, M G; La Bella, G; Tozzoli, R; Caprioli, A; La Salandra, G

    2016-10-01

    Shiga toxin-producing Escherichia coli (STEC) are a significant food-borne public health hazard in Europe, where most human infections are associated with 5 serogroups (O157, O26, O103, O145, and O111). In 2015, 95 food and environmental samples were examined for the presence of Shiga toxin genes (stx1 and stx2). The STEC were isolated from 2 raw milk and 1 mozzarella cheese samples that were collected in the period between June and September. To the best of our knowledge, this finding represents the first report of STEC isolation from mozzarella cheese produced in Italy, and it suggests that both the quality of raw milk used to produce mozzarella and the thermal inactivation treatment associated with the curd-stretching step should be carefully monitored. PMID:27522413

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

    SciTech Connect

    McIntyre, B.J.

    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.

  6. 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.

  7. 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

  8. First Principles Calculations of Electrochemically Controlled Hydrogen Mobility and Uptake at the Ni(111)H2O Interface

    SciTech Connect

    C Taylor; R Kelly; M Neurock

    2005-11-14

    The binding of hydrogen on Ni(111) in the presence of an water is considered using both a bilayer and a saturated model of the solvent environment. The presence of a water bilayer did not change the binding energies or geometry of hydrogen on the Ni(111) compared to adsorption in ultra-high vacuum. Using the saturated model (four bilayers over the surface) we also monitored the change in hydrogen binding as a function of electrochemical potential. Binding energies for hydrogen at the hcp and octahedral sites shifted endothermically as the potential was made more anodic, indicating that reductive partial charge transfer occurs. Binding at the tetrahedral site was found to be partially oxidizing. Calculation of vibrational modes allowed the extrapolation of ab initio results to ambient and elevated temperatures. Surface Pourbaix diagrams were constructed illustrating the stability of various phases on the Ni(111) surface as a function of pH and potential.

  9. Short communication: Isolation of Shiga toxin-producing Escherichia coli in raw milk and mozzarella cheese in southern Italy.

    PubMed

    Nobili, G; Franconieri, I; Basanisi, M G; La Bella, G; Tozzoli, R; Caprioli, A; La Salandra, G

    2016-10-01

    Shiga toxin-producing Escherichia coli (STEC) are a significant food-borne public health hazard in Europe, where most human infections are associated with 5 serogroups (O157, O26, O103, O145, and O111). In 2015, 95 food and environmental samples were examined for the presence of Shiga toxin genes (stx1 and stx2). The STEC were isolated from 2 raw milk and 1 mozzarella cheese samples that were collected in the period between June and September. To the best of our knowledge, this finding represents the first report of STEC isolation from mozzarella cheese produced in Italy, and it suggests that both the quality of raw milk used to produce mozzarella and the thermal inactivation treatment associated with the curd-stretching step should be carefully monitored.

  10. 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.

  11. Li{sup +}-ion neutralization on metal surfaces and thin films

    SciTech Connect

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

    2011-11-15

    Li{sup +} 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.

  12. Radioisotope labeled platelets in medical diagnosis

    SciTech Connect

    Pope, C.F.; Sostman, H.D.

    1986-08-01

    The myriad of applications of indium-111 labeled platelets (/sup 111/In-P), both in biomedical research and clinical diagnostic imaging, in recent years is an index of the potential of this technology. Because many diseases involve the vascular system, a nontoxic platelet label suitable for imaging has immense potential for diagnosis. Presently confined to research centers, this technique is currently used in three main diagnostic situations: deep vein thrombosis, cardiac thrombi, and organ (renal) transplantation rejection. Future applications will proliferate when difficulties in achieving rapid labeling are overcome, and the period between study initiation and final diagnosis is diminished. This review emphasizes current clinical applications and the potential role of this technology in diagnostic imaging. 52 references.

  13. 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.

  14. Chemically Accurate Simulation of a Polyatomic Molecule-Metal Surface Reaction

    PubMed Central

    2016-01-01

    Although important to heterogeneous catalysis, the ability to accurately model reactions of polyatomic molecules with metal surfaces has not kept pace with developments in gas phase dynamics. Partnering the specific reaction parameter (SRP) approach to density functional theory with ab initio molecular dynamics (AIMD) extends our ability to model reactions with metals with quantitative accuracy from only the lightest reactant, H2, to essentially all molecules. This is demonstrated with AIMD calculations on CHD3 + Ni(111) in which the SRP functional is fitted to supersonic beam experiments, and validated by showing that AIMD with the resulting functional reproduces initial-state selected sticking measurements with chemical accuracy (4.2 kJ/mol ≈ 1 kcal/mol). The need for only semilocal exchange makes our scheme computationally tractable for dissociation on transition metals. PMID:27284787

  15. Chemically optimized antimyosin Fab conjugates with chelating polymers: importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization.

    PubMed

    Trubetskoy, V S; Narula, J; Khaw, B A; Torchilin, V P

    1993-01-01

    Murine antimyosin Fab fragment was conjugated with 111In-labeled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate. This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.

  16. Population doses from environmental gamma radiation in Iraq

    SciTech Connect

    Marouf, B.A.; Mohamad, A.S.; Taha, J.S.; al-Haddad, I.K. )

    1992-05-01

    The exposure rates due to external gamma radiation were measured in 11 Iraqi governerates. Measurements were performed with an Environmental Monitoring System (RSS-111) in open air 1 m above the ground. The average absorbed dose rate in each governerate was as follows (number x 10(-2) microGy h-1): Babylon (6.0), Kerbala (5.3), Al-Najaf (5.4), Al-Kadysia (6.5), Wasit (6.5), Diala (6.5), Al-Anbar (6.5), Al-Muthana (6.6), Maisan (6.8), Thee-Kar (6.6), and Al-Basrah (6.5). The collective doses to the population living in these governerates were 499, 187, 239, 269, 262, 458, 384, 153, 250, 450, and 419 person-Sv, respectively.

  17. Argon-assisted growth of epitaxial graphene on Cu(111)

    NASA Astrophysics Data System (ADS)

    Robinson, Zachary R.; Tyagi, Parul; Mowll, Tyler R.; Ventrice, Carl A., Jr.; Hannon, James B.

    2012-12-01

    The growth of graphene by catalytic decomposition of ethylene on Cu(111) in an ultrahigh vacuum system was investigated with low-energy electron diffraction, low-energy electron microscopy, and atomic force microscopy. Attempts to form a graphene overlayer using ethylene at pressures as high as 10 mTorr and substrate temperatures as high as 900 ∘C resulted in almost no graphene growth. By using an argon overpressure, the growth of epitaxial graphene on Cu(111) was achieved. The suppression of graphene growth without the use of an argon overpressure is attributed to Cu sublimation at elevated temperatures. During the initial stages of growth, a random distribution of rounded graphene islands is observed. The predominant rotational orientation of the islands is within ±1∘ of the Cu(111) substrate lattice.

  18. [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.

  19. Carotid body tumors: advantages of contrast ultrasound investigation.

    PubMed

    Giannoni, Maria F; Irace, Luigi; Vicenzini, Edoardo; Massa, Rita; Gossetti, Bruno; Benedetti-Valentini, Fabrizio

    2009-10-01

    Carotid body tumors are rare neoplasms that have to be considered in the evaluation of all lateral neck mass. Early surgical removal has been recommended to avoid possible cranial nerve injury, the most common perioperative complication. Computed tomography (CT) and magnetic resonance imaging (MRA) angiographies are the preferred pre-operative diagnostic imaging investigations, as well as the 111 In-pentetreotide scintigraphic scan, whereas the standard ultrasound investigations have poor sensitivity in characterizing of the blood flows of the parenchimal structure of the carotid body tumors. We describe a case of a patient with a carotid body tumor assessed with contrast ultrasonography that clearly improved the quality of the standard color Duplex. This technique may represent a non-invasive method, easy to use and to repeat, and able to achieve high diagnostic accuracy.

  20. Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

    PubMed

    Andres, R Y; Schubiger, P A; Tiefenauer, L; Seybold, K; Locher, J T; Mach, J P; Buchegger, F

    1988-01-01

    Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.

  1. 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.

  2. Interactions at the Al-S-Fe interface: S inhibition of aluminum oxidation

    SciTech Connect

    Addepalli, S.G.; Lin, J.S.; Ekstrom, B.; Kelber, J.A.

    1999-08-01

    The deposition of aluminum on S/Fe(111) (1 x 1) at 300 K in UHV results in the formation of a disordered S-modified Al adlayer. Insertion of Al between the sulfur atoms and the Fe substrate is indicated by an increase of the S Auger signal with increasing Al deposition. Room-temperature oxidation of AlS/Fe(111) in UHV is inhibited compared to the oxidation of aluminum deposited on the sulfur-free Fe(111). The oxygen-uptake curves and variations in the S(LVV), Fe(MVV) intensities with oxygen exposure are also consistent with the insertion of the aluminum atoms between the S overlayer and the Fe substrate.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Role of Quantum and Surface-State Effects in the Bulk Fermi-Level Position of Ultrathin Bi Films.

    PubMed

    Hirahara, T; Shirai, T; Hajiri, T; Matsunami, M; Tanaka, K; Kimura, S; Hasegawa, S; Kobayashi, K

    2015-09-01

    We performed high-resolution photon-energy and polarization-dependent ARPES measurements on ultrathin Bi(111) films [6-180 bilayers (BL), 2.5-70 nm thick] formed on Si(111). In addition to the extensively studied surface states (SSs), the edge of the bulk valence band was clearly measured by using S-polarized light. We found direct evidence that this valence band edge, which forms a hole pocket in the bulk Bi crystal, does not cross the Fermi level for the 180 BL thick film. This is consistent with the predicted semimetal-to-semiconductor transition due to the quantum-size effect [V.B. Sandomirskii, Sov. Phys. JETP 25, 101 (1967)]. However, it became metallic again when the film thickness was decreased (below 30 BL). A plausible explanation for this phenomenon is the modification of the charge neutrality condition due to the size effect of the SSs. PMID:26382694

  8. Society of Nuclear Medicine--57th annual meeting.

    PubMed

    Searle, Ben

    2010-08-01

    The 57th Annual Meeting of the Society of Nuclear Medicine, held in Salt Lake City, UT, USA, included topics covering new developments in imaging agents and radiopharmaceutical therapies in the field of nuclear medicine. This conference report highlights selected presentations related to imaging of the brain, the prediction of heart disease, and the detection and treatment of various cancers. Investigational drugs discussed include TF-2 plus [68Ga]IMP-288 and TF-2 plus [111In]IMP-288 (both Immunomedics Inc), [11C]PBR-170 (Royal Prince Alfred Hospital/Australian Nuclear Science & Technology Organization), [11C]LY-2795050 (Eli Lilly & Co), yttrium (90Y) clivatuzumab tetraxetan (Garden State Cancer Center/Immunomedics Inc), [18F]LMI-1195 (Lantheus Medical Imaging Inc), fluciclovine (18F) (GE Healthcare/Nihon Medi-Physics Co Ltd), [99mTc]MIP-1340 and [99mTc]MIP-1407 (both Molecular Insight Pharmaceuticals Inc).

  9. Diagnosis of osteomyelitis in the presence of soft-tissue infection and radiologic evidence of osseous abnormalities: Value of leukocyte scintigraphy

    SciTech Connect

    Jacobson, A.F.; Harley, J.D.; Lipsky, B.A.; Pecoraro, R.E. )

    1991-10-01

    To evaluate the usefulness of 111In-leukocyte scintigraphy for identifying osteomyelitis in the presence of soft-tissue infection, the author prospectively studied 45 bone sites adjacent to soft-tissue infection in patients with abnormal findings on radiographs and 99mTc bone scans that were suggestive of osteomyelitis. 111In-leukocyte scans were analyzed in terms of the intensity of abnormal uptake and its location relative to bone. The diagnosis of osteomyelitis was established from results of percutaneous bone biopsy culture (n = 35), histologic examination of surgical specimens (n = 8), and clinical follow-up (n = 2). Osteomyelitis was present at 22 sites, including 16 of 18 sites with increased leukocyte uptake in bone, resulting in a sensitivity of 73%, specificity of 91%, and positive predictive value of 89% for this finding. Osteomyelitis was present at four of 17 sites with predominantly soft-tissue localization of leukocyte activity in the region of bone, none of seven sites with normal leukocyte scans, and two of three sites with diminished leukocyte uptake in bone. Although not helpful in distinguishing infectious from noninfectious bone abnormalities, 3- and especially 24-hr bone scans viewed in conjunction with leukocyte studies provided important correlation to aid in estimating the location of focal abnormal leukocyte uptake. The finding of soft-tissue infection with increased uptake of labeled leukocytes that extends to involve adjacent bone strongly suggests concurrent osteomyelitis. When the presence of abnormal leukocyte uptake in bone is uncertain, additional imaging and possibly biopsy may be required to establish or exclude the diagnosis of osteomyelitis.

  10. The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody.

    PubMed Central

    Davidson, B. R.; Babich, J.; Young, H.; Waddington, W.; Clarke, G.; Short, M.; Boulos, P.; Styles, J.; Dean, C.

    1991-01-01

    This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule. Patients undergoing immunoscintigraphy with 111In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC). The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity. These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound 111In does not reduce the liver uptake of radioactivity. PMID:1931605

  11. Structural switching of Cu,Zn-superoxide dismutases at loop VI: insights from the crystal structure of 2-mercaptoethanol-modified enzyme

    PubMed Central

    Ihara, Kentaro; Fujiwara, Noriko; Yamaguchi, Yoshiki; Torigoe, Hidetaka; Wakatsuki, Soichi; Taniguchi, Naoyuki; Suzuki, Keiichiro

    2012-01-01

    Cu,Zn SOD1 (superoxide dismutase 1) is implicated in FALS (familial amyotrophic lateral sclerosis) through the accumulation of misfolded proteins that are toxic to neuronal cells. Loop VI (residues 102–115) of the protein is at the dimer interface and could play a critical role in stability. The free cysteine residue, Cys111 in the loop, is readily oxidized and alkylated. We have found that modification of this Cys111 with 2-ME (2-mercaptoethanol; 2-ME-SOD1) stabilizes the protein and the mechanism may provide insights into destabilization and the formation of aggregated proteins. Here, we determined the crystal structure of 2-ME-SOD1 and find that the 2-ME moieties in both subunits interact asymmetrically at the dimer interface and that there is an asymmetric configuration of segment Gly108 to Cys111 in loop VI. One loop VI of the dimer forms a 310-helix (Gly108 to His110) within a unique β-bridge stabilized by a hydrogen bond between Ser105-NH and His110-CO, while the other forms a β-turn without the H-bond. The H-bond (H-type) and H-bond free (F-type) configurations are also seen in some wild-type and mutant human SOD1s in the Protein Data Bank suggesting that they are interconvertible and an intrinsic property of SOD1s. The two structures serve as a basis for classification of these proteins and hopefully a guide to their stability and role in pathophysiology. PMID:22804629

  12. 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.

  13. 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.

  14. Theranostics with Multifunctional Magnetic Gold Nanoshells: Photothermal Therapy and T2* Magnetic Resonance Imaging

    PubMed Central

    Melancon, Marites P.; Elliott, Andrew; Ji, Xiaojun; Shetty, Anil; Yang, Zhi; Tian, Mei; Taylor, Brian; Stafford, R. Jason; Li, Chun

    2012-01-01

    Objectives To investigate the multifunctional imaging and therapeutic capabilities of core-shell nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and a gold shell (SPIO@AuNS). Materials and Methods The magnetic/optical properties of SPIO@AuNS were examined both in an agar gel phantom and in vivo by evaluating contrast-enhanced MRI and by measuring near-infrared (NIR) light-induced temperature changes mediated by SPIO@AuNS. In addition, the biodistribution and pharmacokinetics of 111In-labeled SPIO@AuNS after intravenous injection in mice bearing A431 tumors were evaluated in the presence and absence of an external magnet. Results In agar phantoms containing SPIO@AuNS, a significant contrast enhancement in T2-weighted MRI was observed and a linear increase in temperature was observed with increasing concentration and laser output power when irradiated with NIR light centered at an 808-nm. In vivo, T2*-MRI delineated SPIO@AuNS and magnetic resonance temperature imaging of the same tumors revealed significant temperature elevations when intratumorally injected with SPIO@AuNS (1 × 1011 particles/mouse) and irradiated with NIR light (65.70 ± 0.69°C vs. 44.23 ± 0.24°C for saline + laser). Biodistribution studies in mice intravenously injected with 111In-labeled-SPIO@AuNS(1 × 1013 particles/mouse) had an approximately 2-fold increase in SPIO@AuNS delivered into tumors in the presence of an external magnet compared to tumors without the magnet. Conclusions Owing to its ability to mediate efficient photothermal ablation of cancer cells under MRI guidance, as well as the ability to be directed to solid tumors with an external magnetic field gradient, multifunctional SPIO@AuNS is a promising theranostic nano-platform. PMID:21150791

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

    SciTech Connect

    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.

  16. Color Doppler Ultrasound and Gamma Imaging of Intratumorally Injected 500 nm Iron-Silica Nanoshells

    PubMed Central

    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.

    2013-01-01

    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 non-biodegradable SiO2 and biodegradable Fe-SiO2 nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with 111In3+ 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-111In labeling for studying silica nanoparticle biodistributions. PMID:23802554

  17. 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.

  18. In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma

    PubMed Central

    Matera, Lina; Galetto, Alessandra; Bello, Marilena; Baiocco, Cinzia; Chiappino, Isabella; Castellano, Giancarlo; Stacchini, Alessandra; Satolli, Maria A; Mele, Michele; Sandrucci, Sergio; Mussa, Antonio; Bisi, Gianni; Whiteside, Theresa L

    2006-01-01

    Background Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC). Adherent NK (A-NK) cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v.) versus locoregional (intraarterial, i.a.) routes. Patients and methods A-NK cells expanded ex-vivo with IL-2 and labeled with 111In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of 111In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate. Results A-NK cells expressed a donor-dependent CD56+CD16+CD3- (NK) or CD56+CD16+CD3+ (NKT) phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections. Conclusion This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site. PMID:17105663

  19. Improved tumor localization with increasing dose of indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer

    SciTech Connect

    Patt, Y.Z.; Lamki, L.M.; Haynie, T.P.; Unger, M.W.; Rosenblum, M.G.; Shirkhoda, A.; Murray, J.L.

    1988-08-01

    Monoclonal antibodies (MoAbs) against carcinoembryonic antigen (CEA) react with human colorectal cancer cells, and when labeled with a gamma-emitting radioisotope, may help to localize known and occult metastatic disease. We tested ZCE-025, a high-affinity immune gamma globulin1 (IgG1) MoAb anti-CEA that does not react with normal granulocyte glycoproteins in a phase I/II trial to determine the reagent's toxicity and its maximum efficacy in detecting metastatic colorectal cancer. Increasing doses of unlabeled ZCE-025 were mixed with 1 mg of Indium-111 (111In)-radiolabeled MoAb and administered intravenously (IV) to 34 patients who had metastatic colorectal cancer. Planar nuclear or single photon emission computed tomographic (SPECT) scans were performed 48 to 72 and 120 to 144 hours later. Total dose of MoAb and scanning sensitivity (number of imaged lesions/number of known lesions) were correlated up to 80 mg. At doses of 2.5 to 20 mg, a mean of 22% of the lesions were imaged; at 40 mg, 77% were imaged (P less than .01). Liver metastases were detected as areas of increased activity (hot) at the 40 mg dose but showed decreased MoAb uptake at lower doses. At the 40 mg dose normal liver parenchymal uptake of the labeled MoAb was lower with respect to blood pool compared with the other doses. At 80 mg, however, sensitivity of detection declined to 21%. One milligram of 111In-labeled ZCE-025 antibody coinfused with 39 mg of unlabeled antibody appeared optimal for detecting metastatic colorectal cancer, particularly in the liver. Although the exact mechanism(s) for this dose effect is currently unknown, a partial blocking effect of unlabeled antibody with a change in MoAb biodistribution may be occurring.

  20. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model.

    PubMed

    Froidevaux, Sylvie; Eberle, Alex N; Christe, Martine; Sumanovski, Lazar; Heppeler, Axel; Schmitt, Jörg S; Eisenwiener, Klaus; Beglinger, Christoph; Mäcke, Helmut R

    2002-04-20

    Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.

  1. 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

  2. Influence of molecular design on biodistribution and targeting properties of an Affibody-fused HER2-recognising anticancer toxin.

    PubMed

    Altai, Mohamed; Liu, Hao; Orlova, Anna; Tolmachev, Vladimir; Gräslund, Torbjörn

    2016-09-01

    Targeted delivery of toxins is a promising way to treat disseminated cancer. The use of monoclonal antibodies as targeting moiety has provided proof-of-principle for this approach. However, extravasation and tissue penetration rates of antibody-based immunotoxins are limited due to antibody bulkiness. The use of a novel class of targeting probes, Affibody molecules, provides smaller toxin-conjugated constructs, which may improve targeting. Earlier, we have demonstrated that affitoxins containing a HER2-targeting Affibody moiety and a deimmunized and truncated exotoxin A from Pseudomonas aeruginosa, PE38X8, provide highly selective toxicity to HER2-expressing cancer cells. To evaluate the influence of molecular design on targeting and biodistribution properties, a series of novel affitoxins were labelled with the residualizing radionuclide 111In. In this study, we have shown that the novel conjugates are more rapidly internalized compared with the parental affitoxin. The use of a (HE)3 purification tag instead of a hexahistidine tag enabled significant (p<0.05) reduction of the hepatic uptake of the affitoxin in a murine model. Fusion of the affitoxin with an albumin-binding domain (ABD) caused appreciable extension of the residence time in circulation and several-fold reduction of the renal uptake. The best variant, 111In-(HE)3-ZHER2-ABD-PE38X8, demonstrated receptor-specific accumulation in HER2-expressing SKOV-3 xenografts. In conclusion, a careful molecular design of scaffold protein based anticancer targeted toxins can appreciably improve their biodistribution and targeting properties. PMID:27573289

  3. 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.

  4. 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.

  5. Quantification of internalization of EGFR-binding Affibody molecules: Methodological aspects.

    PubMed

    Göstring, Lovisa; Chew, Ming Tsuey; Orlova, Anna; Höidén-Guthenberg, Ingmarie; Wennborg, Anders; Carlsson, Jörgen; Frejd, Fredrik Y

    2010-04-01

    Tumor cell internalization of targeting agents is of interest, since internalization influences the local retention time of a radionuclide and thereby imaging quality in PET and SPECT and effects of radionuclide therapy. In cases where nuclear methods are not applicable at the cellular level, quantitative fluorescent techniques are useful as described in this article. Two fluorescence-based methods to study cellular internalization were applied: the CypHer and the Alexa488-quenching methods, both utilized in fluorescence microscopy and flow cytometry. Two EGFR-binding Affibody molecules were analyzed in A431 cells: the monomer Z1907 and the dimer (Z1907)2. EGF, cetuximab and non-specific Affibody molecules were used as controls. For comparison, internalization of 111In-labeled Z1907 was studied with the acid wash internalization assay. The Cypher method is straightforward, but requires equal labeling of all compounds for accurate quantification. The Alexa488-quenching method is preferable since it is independent of the dye-to-protein ratio. According to this method, about 45% of EGF and 19-24% of the bound Affibody molecules and cetuximab were internalized within one hour. Similar results were seen with 111In-Z1907 in the acid wash method, while (Z1907)2 was not removed by acid and thus could not be studied this way. The fluorescence-based Alexa488-quenching method is well suited to quantitatively analyze internalization of targeting agents, also those that resist acid wash. The internalized fraction showed that both the monomeric and dimeric Affibody molecules are expected to give good uptake and thereby good retention of metallic radionuclides which will render good tumor to background values. PMID:20198317

  6. Inhibition of experimental pulmonary metastasis by controlling biodistribution of catalase in mice.

    PubMed

    Nishikawa, Makiya; Tamada, Ayumi; Kumai, Hitomi; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2002-05-20

    In a previous study, we showed that targeted delivery of bovine liver catalase to hepatocytes by direct galactosylation augmented the inhibitory effect of the enzyme on experimental hepatic metastasis of colon carcinoma cells (unpublished data). Here, we examined the ability of catalase to inhibit tumor metastasis to the lung by controlling its biodistribution. Four types of catalase derivative, Gal-CAT, Man-CAT, Suc-CAT and PEG-CAT, were synthesized. Experimental pulmonary metastasis was induced in mice by i.v. injection of 1 x 10(5) colon 26 tumor cells. An i.v. injection of catalase (35,000 units/kg) partially, but significantly, decreased the number of colonies in the lung 2 weeks after tumor injection, from 93 +/- 29 (saline injection) to 63 +/- 23 (p < 0.01). Suc-CAT, Man-CAT and Gal-CAT showed effects similar to those of catalase on the number of colonies. However, PEG-CAT greatly inhibited pulmonary metastasis to 22 +/- 11 (p < 0.001). Furthermore, s.c. injection of catalase also greatly inhibited metastasis (11 +/- 6, p < 0.001). Neither inactivated catalase nor BSA showed any effects on the number of metastatic colonies, indicating that the enzymatic activity of catalase to detoxify H(2)O(2) is the critical factor inhibiting metastasis. (111)In-PEG-CAT showed a sustained concentration in plasma, whereas s.c.-injected (111)In-catalase was slowly absorbed from the injection site. These results suggest that retention of catalase activity in the circulation is a promising approach to inhibit pulmonary metastasis. PMID:11992420

  7. 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

  8. 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. PMID:27479790

  9. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    PubMed

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications. PMID:24505235

  10. 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. PMID:18688854

  11. Selective uptake and imaging of aptamer- and antibody-conjugated hollow nanospheres targeted to epidermal growth factor receptors overexpressed in head and neck cancer.

    PubMed

    Melancon, Marites Pasuelo; Zhou, Min; Zhang, Rui; Xiong, Chiyi; Allen, Peter; Wen, Xiaoxia; Huang, Qian; Wallace, Michael; Myers, Jeffrey N; Stafford, R Jason; Liang, Dong; Ellington, Andrew D; Li, Chun

    2014-05-27

    The purpose of this study was to compare the binding affinity and selective targeting of aptamer- and antibody-coated hollow gold nanospheres (HAuNS) targeted to epidermal growth factor receptors (EGFR). EGFR-targeting aptamers were conjugated to HAuNS (apt-HAuNS) by attaching a thiol-terminated single-stranded DNA to the HAuNS and then adding the complementary RNA targeted to EGFR. Apt-HAuNS was characterized in terms of size, surface charge, absorption, and number of aptamers per particle. The in vivo pharmacokinetics, in vivo biodistribution, and micro-SPECT/CT imaging of (111)In-labeled apt-HAuNS and anti-EGFR antibody (C225)-conjugated HAuNS were evaluated in nude mice bearing highly malignant human OSC-19 oral tumors. (111)In-labeled PEG-HAuNS was used as a control (n = 5/group). Apt-HAuNS did not have an altered absorbance profile or size (λmax = 800 nm; diameter = 55 nm) compared to C225-HAuNS or PEG-HAuNS. The surface charge became more negative upon conjugation of the aptamer (-51.4 vs -19.0 for PEG-HAuNS and -25.0 for C225-HAuNS). The number of aptamers/particle was ∼250. In vitro cell binding and in vivo biodistribution showed selective binding of the apt-HAuNS to EGFR. μSPECT/CT imaging confirmed that there was more tumor uptake of apt-HAuNS than C225-HAuNS. Aptamer is a promising ligand for image-guided delivery of nanoparticles for treatment of tumor cells overexpressing EGFR.

  12. Influence of molecular design on biodistribution and targeting properties of an Affibody-fused HER2-recognising anticancer toxin.

    PubMed

    Altai, Mohamed; Liu, Hao; Orlova, Anna; Tolmachev, Vladimir; Gräslund, Torbjörn

    2016-09-01

    Targeted delivery of toxins is a promising way to treat disseminated cancer. The use of monoclonal antibodies as targeting moiety has provided proof-of-principle for this approach. However, extravasation and tissue penetration rates of antibody-based immunotoxins are limited due to antibody bulkiness. The use of a novel class of targeting probes, Affibody molecules, provides smaller toxin-conjugated constructs, which may improve targeting. Earlier, we have demonstrated that affitoxins containing a HER2-targeting Affibody moiety and a deimmunized and truncated exotoxin A from Pseudomonas aeruginosa, PE38X8, provide highly selective toxicity to HER2-expressing cancer cells. To evaluate the influence of molecular design on targeting and biodistribution properties, a series of novel affitoxins were labelled with the residualizing radionuclide 111In. In this study, we have shown that the novel conjugates are more rapidly internalized compared with the parental affitoxin. The use of a (HE)3 purification tag instead of a hexahistidine tag enabled significant (p<0.05) reduction of the hepatic uptake of the affitoxin in a murine model. Fusion of the affitoxin with an albumin-binding domain (ABD) caused appreciable extension of the residence time in circulation and several-fold reduction of the renal uptake. The best variant, 111In-(HE)3-ZHER2-ABD-PE38X8, demonstrated receptor-specific accumulation in HER2-expressing SKOV-3 xenografts. In conclusion, a careful molecular design of scaffold protein based anticancer targeted toxins can appreciably improve their biodistribution and targeting properties.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

    2015-11-01

    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

  18. 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

    2015-11-01

    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

  19. Intracellular routing in breast cancer cells of streptavidin-conjugated trastuzumab Fab fragments linked to biotinylated doxorubicin-functionalized metal chelating polymers.

    PubMed

    Liu, Peng; Cai, Zhongli; Kang, Jae W; Boyle, Amanda J; Adams, Jarret; Lu, Yijie; Ngo Ndjock Mbong, Ghislaine; Sidhu, Sachdev; Reilly, Raymond M; Winnik, Mitchell A

    2014-03-10

    We describe the synthesis of a heterotelechelic metal-chelating polymer (Bi-MCP-Dox), a polyacrylamide with a number average degree of polymerization DPn = 50 (PDI = 1.2), with biotin (Bi) and doxorubicin (Dox) as functional chain ends and diethylenetriaminepentaacetic acid (DTPA) pendant groups as the binding sites for metal ions. We compared its behavior in cell-uptake experiments with a similar polymer (Bi-MCP) without Dox. These MCPs were complexed with trastuzumab Fab (tmFab) fragments covalently linked to streptavidin (SAv) to form tmFab-SAv-Bi-MCP-Dox and tmFab-SAv-Bi-MCP via the strong affinity between Bi and SAv. tmFab targets human epidermal growth factor receptor-2 (HER2), which is overexpressed on certain human breast cancer cells. Surface plasmon resonance (SPR) experiments with the extracellular domain (ECD) of HER2 showed that incorporation of the MCPs in these complexes had no significant effect on the association or dissociation rate with the HER2 ECD and the dissociation constants. The tmFab-complexed MCPs were subsequently labeled with (111)In (an Auger electron emitting radionuclide). Auger electrons can cause lethal DNA double strand breaks (DSBs) but only if they are emitted intracellularly and especially, in close proximity to the nucleus. To evaluate the cellular and nuclear uptake of tmFab-SAv-Bi-MCP-Dox, we incubated HER2+ SK-BR-3 human breast cancer cells with the complexes saturated with stable In(3+) and visualized their distribution by confocal fluorescence microscopy, monitoring the fluorescence of Dox. In parallel, we carried out cell fractionation studies on tmFab-SAv-Bi-MCP-Dox and on tmFab-SAv-Bi-MCP labeled with (111)In. Both radiolabeled complexes showed cell internalization and nuclear localization. We conclude that metal-chelating polymers with this composition appear to encourage internalization, nuclear uptake, and chromatin (DNA) binding of trastuzumab fragments modified with streptavidin in human breast cancer cells

  20. Radionuclide therapy in neuroendocrine tumours: a systematic review.

    PubMed

    Gulenchyn, K Y; Yao, X; Asa, S L; Singh, S; Law, C

    2012-05-01

    The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be