The method of whole-body autoradiography (WBAR) offers unusual promise as a powerful in vivo tool to improve on the resolving ability for tunor radioantibody localization in animal tumor models, compared with alternative methods in current use such as gamma scintigraphy and tissue counting. To meet these requirements, WBAR appears to have the necessary spatial resolving capabilities, avoids preselection of tumor-to-nontumor tissues, eliminates dissection artifacts, and permits quantitative historadiologic analysis of tumor targeting by radioantibodies. The major goals of this investigation will be pursued by study of the following: (1) qualitative and quantitative study by WBAR of the in vivo organ and tissue biodistribution of radiolabeled goat anti-CEA IgG and monoclonal anti-CEA IgG in hamsters and nude mice bearing heterotransplants of human CEA-producing GW-39 tumors; (2) quantitation of the ARG records by the method of high-resolution computer-assisted videodensitometry for correlation with tissue counting data; (3) correlation of the WBAR pattern of biodistribution of radiolabeled polyclonal and monoclonal anti-CEA, anti-CSAp with tumor size, morphology, degree of differentiation, mucin content, antigen-secreting capacity and site(s) of implantation of tumor xenografts; (4) use of double radionuclide ARG techniques in order to assess the viability of tumor regions (2-deoxyglucose uptake) for correlation with patterns of differenital tumor affinities for uptake of radiolabeled polyclonal and monoclonal antibodies; (5) attempt to optimize tumor specific uptake of radioantibodies by varying dose regimens (single vs. multiple doses) and by undertaking tumor-saturation binding studies; (6) comparison of the WBAR biodistribution of radiolabeled monoclonal antibody, polyclonal antibody, and their labeled fragments (Fab, F[ab112), directed to the same tumor in 2 different hosts: the nude mouse and the hamster; (7) visualization of the WBAR pattern of radioantibody distribution developing in xenografted tumors following introduction of labeled monoclonal antibodies directed against different epitopes on the same antigen or against different antigens.
| Fand, I; Sharkey, R M; Grundy, J P et al. (1992) Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model. Int J Rad Appl Instrum B 19:87-99 |
| Coderre, J A; Glass, J D; Fairchild, R G et al. (1990) Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumors other than melanoma. Cancer Res 50:138-41 |
| Fand, I; Sharkey, R M; Goldenberg, D M (1990) Use of whole-body autoradiography in cancer targeting with radiolabeled antibodies. Cancer Res 50:885s-891s |
| Sharkey, R M; Kaltovich, F A; Shih, L B et al. (1988) Radioimmunotherapy of human colonic cancer xenografts with 90Y labeled monoclonal antibodies to carcinoembryonic antigen. Cancer Res 48:3270-5 |
| Coderre, J A; Glass, J D; Fairchild, R G et al. (1987) Selective targeting of boronophenylalanine to melanoma in BALB/c mice for neutron capture therapy. Cancer Res 47:6377-83 |
