The goal is to develop improved diagnostic imaging agents for human melanoma based on a radio-labeled monoclonal antibody. P97 and HMW are oncofetal antigens present on human melanoma tumor cells. Studies in nude mice have shown there is active concentration of both antibodies (and Fab fragments) directed against these antigens of human melanoma. Tumor labeling is antigen specific, as documented by comparisons with radiolabeled control immunoglobulin and immune fragments. Patients have been studied with whole antibody and fragments, and uptake has been documented in metastatic lesions. About 80% of documented metastatic lesions have been imaged, and antigen-specific uptake in tumor has been documented by comparison to radiolabeled control immunoglobulin. Maximum target-to-nontarget ratios observed from human tumors, biopsied at 72 hrs after intravenous administration of antibody, were 7 to 1. Fifty-five patients with advanced malignant melanoma have been studied. In addition, antibody imaging of metastatic melanoma in lymph nodes (immunolymphoseintigraphy) has begun. Antibody fragments are injected subcutaneously. In this case diseased nodes show both specific and non-specific localization of murine immunoglobulin. We are studying the details of antibody radiolabeling methods and have determined optimum conditions for preserving the immunoreactivity of labeled antibodies in relation to iodine/antibody molar ratios and all other reaction conditions, and have designed techniques to minimize radiolysis of final product. We are beginning work with antibody directed against non-small cell carcinoma of the lung. (2)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029639-06
Application #
3168804
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1984-08-01
Project End
1987-12-31
Budget Start
1986-08-01
Budget End
1987-12-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Brooks, Jennifer D; Boice Jr, John D; Stovall, Marilyn et al. (2012) Reproductive status at first diagnosis influences risk of radiation-induced second primary contralateral breast cancer in the WECARE study. Int J Radiat Oncol Biol Phys 84:917-24
Eary, J F; Schroff, R W; Abrams, P G et al. (1989) Successful imaging of malignant melanoma with technetium-99m-labeled monoclonal antibodies. J Nucl Med 30:25-32
Eary, J F; Appelbaum, F L; Durack, L et al. (1989) Preliminary validation of the opposing view method for quantitative gamma camera imaging. Med Phys 16:382-7
Kishore, R; Eary, J F; Krohn, K A et al. (1986) Autoradiolysis of iodinated monoclonal antibody preparations. Int J Rad Appl Instrum B 13:457-9
Beaumier, P L; Krohn, K A; Carrasquillo, J A et al. (1985) Melanoma localization in nude mice with monoclonal Fab against p97. J Nucl Med 26:1172-9