RADIOLABELED MONOCLONAL ANTIBODY IMAGING OF TUMORS

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Summary of Work: 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 staff. They are then administered to patients under the supervision of a nuclear medicine physician and an assistant in the Nuclear Medicine Department. Serial blood samples, urine specimens, and often bone marrow or tumor biopsies are obtained to evaluate the distribution of the monoclonal antibody in the body. The phase I trial with B3, in collaboration with Dr. Ira Pastan, is continuing patient accrual. We have accrued 25 patients at our fourth dose level. Based on the preliminary results of our collaborative radioimmunotherapy trial with Dr. Waldmann in which we used humanized anti-tac monoclonal antibody, we have started two trials using Ca-DTPA to sequester any free Y-90 that comes from the antibody. The DTPA is expected to chelate free Y-90 on this to minimize the concentration of Y-90 in the bone marrow, which should allow higher doses of Y-90 anti- Tac to be administered. We have studied four patients. We have been developing the use of anti-Tac dsFv in collaboration with Dr. Ira Pastan and Dr. Eckelman of the Positron Emission Tomography (PET) Department. We have shown that the high renal uptake can be blocked using a commercially available amino acid solution. These studies were performed using Aminosyn bolus and infusion in baboons receiving radio-labeled dsFv. Quantitation with PET (F-18 ati-Tac dsFv) showed that renal blocking was effective. Imaging studies comparing the use of Tc-99m anti-CEA Fab (FDA approved) and F-18 deoxyglucose have been started in patients with previous history of colorectal carcinoma and rising CEA without evidence of disease by conventional radiographic modalities. In collaboration with M. Brechbiel and the NCI Radiation Oncology group, we have evaluated in a nude mice mode the stability and biodistribution of four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA (CHX-DTPA). We have documented that subtle differences in stereochemistry can cause significant different in stability of Y-90 labeled CHX. From the four sterosiomers we have selected the most stable for Y-90 chelation as our preferred chelate for antibody trials.