These studies are designed to develop improved methods for detecting and treating malignancies. Our group performs preclinical evaluation of antibodies that appear to be promising after initial screening by various laboratories at the National Cancer Institute and develops these antibodies for clinical application. The clinical trials evaluating their pharmacokinetics and dosimetry are performed by our group. A collaborative radioimmunotherapy trial with Dr. Waldmann (PI), in which we used humanized anti-tac monoclonal antibody, is ongoing. A collaborative radioimmunotherapy trial with bone marrow support is ongoing with NCI(Dr, Bishop and Pastan). Various protocols using [F-18] FDG in PET and [O-15] water for tumor detection, followup, and blood flow measurements are ongoing with NCI surgery Branch (Dr. Libutti). There are 4 ongoing collaborative studies evaluating fluorodeoxyglucose-PET for assessing tumor response to treatment (Dr. Swain, Dr. Mackall, Dr. Sausville and Dr. Wilson). We have evaluated the use of fluorodeoxyglucose-PET in assesing sites of viral replication in patients with HIV (Dr. Brust). We have utilized FDG-PET to evaluate sites of metabolic activity in patients with systemic lupus erythematosus. We have perfomed preclinical studies evaluating pretargeting of antibodies for tumor therapy and have demonstrated therapeutic responses with Y-90 and Bi-213 in animal tumor models. Two antibody -strepavidin conjugates have been evaluated preclinically and paper have been accepted for publication. We are evaluating a third anti-mesothelin-strepavidin conjugated antibody.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000417-09
Application #
6675158
Study Section
(NMRR)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Brust, Douglas; Polis, Michael; Davey, Richard et al. (2006) Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation. AIDS 20:495-503
Zhang, YuJian; Xiang, Laiman; Hassan, Raffit et al. (2006) Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice. Clin Cancer Res 12:4695-701
Rao, V Koneti; Carrasquillo, Jorge A; Dale, Janet K et al. (2006) Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS). Am J Hematol 81:81-5
Mamede, Marcelo; Carrasquillo, Jorge A; Chen, Clara C et al. (2006) Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites. Nucl Med Commun 27:31-6
Zhang, Meili; Yao, Zhengsheng; Zhang, Zhuo et al. (2006) The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia. Cancer Res 66:8227-32
Brust, Douglas; Polis, Michael; Davey, Richard et al. (2006) Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation. AIDS 20:985-93
Sato, Noriko; Hassan, Raffit; Axworthy, Donald B et al. (2005) Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv-streptavidin fusion protein. J Nucl Med 46:1201-9
Yao, Zhengsheng; Zhang, Meili; Garmestani, Kayhan et al. (2004) Pretargeted alpha emitting radioimmunotherapy using (213)Bi 1,4,7,10-tetraazacyclododecane-N,N',N"",N""'-tetraacetic acid-biotin. Clin Cancer Res 10:3137-46
Sundaram, Senthil K; Freedman, Nanette M T; Carrasquillo, Jorge A et al. (2004) Simplified kinetic analysis of tumor 18F-FDG uptake: a dynamic approach. J Nucl Med 45:1328-33
McCart, J Andrea; Mehta, Navneet; Scollard, Deborah et al. (2004) Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: molecular imaging after systemic delivery using 111In-pentetreotide. Mol Ther 10:553-61

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