These antibody studies are designed to develop improved methods for detecting and treating malignancies. Our group performs preclinical evaluation of radiolabeled antibodies that appear to be promising after initial screening. The clinical trials evaluating their pharmacokinetics and dosimetry are performed by our group. Two collaborative radioimmunotherapy trial with Dr. Waldmann (PI), in which we used humanized anti-tac monoclonal antibody, are ongoing. In order increase the radioactive dose delivered to tumors and improve the tumor to non-tumor ratios we are pursuing a pretargeting approaches were the antibody with strepavidin is delivered without any radioactivity and after it targets the tumor a radiolabeled biotin is injected. This allows the small radiolabeled bioitin to rapidly localize in tumor or be rapidly excreted. The 2 antibodies we have focused on are B3 and anti-mesothelin (developed in Dr. Pastan's lab).These pretargeting studies have evaluated Y-90 and Bi-213. Dr. Paik has focused his chemistry work on the chemical modification of spherical polymers (PAMAM dendrimers) as carriers of radionuclides and biological molecules. In addition Dr. Paik and has developed a simple purification method for Y-86 that is produce by the NIH PET department. This Y-86 is planned to be used for dosimetry of antibodies radiolabeled with Y-90 that are currently being used by our group. 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 several 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 and have noted intersting changes in nodal visualization in patients with AIDs(Dr. Brust). We are utilizing fluorodeoxyglucose PET in attemps to localize sites of activated lymphomcytes. In one study we utilized FDG-PET to evaluate sites of metabolic activity in patients with systemic lupus erythematosus with active versus inactive disease. We are also evaluting the ability of FDG-PET to differentiate between patients with benign versus lymphomatous adenopathy in the setting of autoimmune lymphoprolifertive syndrome versus.
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