The use of biologic and synthetic polymers to facilitate the transport of chemotherapeutic agents to tumors in now a well-established protocol. Marked increases in therapeutic efficacy have been claimed for polymer-drug combinations compared to """"""""free"""""""" drug. Furthermore macromolecules tagged with radioisotopes or fluorescent probes have shown enhanced uptake in malignant tissue compared to non-malignant tissue. When a macromolecule is used to facilitate transport of a pharmaceutical the process is termed """"""""piggyback pinocytosis"""""""" (or """"""""piggyback endocytosis""""""""). Elevated endocytosis rates are recognized as one of the true physical-chemical differences between tumors and non-malignant cells. This proposal suggests how """"""""piggyback"""""""" transport might be exploited as an imaging modality. Three classes of readily radioiodinated heterocyclics will be bound by intercalation and by covalent attachment to three classes of macromolecules: DNA, human serum albumin, and polylysine. The study will compare the uptake of the polymer-radiopharmaceutical combination to that of the """"""""free"""""""" radiopharmaceutical in a hamster melanoma and a Morris hepatoma in a Buffalo rat. Not only is there the potential to develop a general tumor-imaging radiopharmaceutical but also the possibility to develop an improved polymer-chemotherapeutic combination with enhanced uptake in malignancies.
| Fitzpatrick, D A; Heindel, N D; Egolf, R A et al. (1989) Radiosensitization of human colorectal tumor cells by 4-nitro-5-sulfonatoimidazoles. Radiat Res 117:47-58 |
| Borlinghaus, K P; Fitzpatrick, D A; Heindel, N D et al. (1987) Radiosensitizer conjugation to the carcinoma 19-9 monoclonal antibody. Cancer Res 47:4071-5 |
| Heindel, N D; Van Dongen, J M; Fitzpatrick, D A et al. (1987) Macromolecular attachment as a metabolic stabilizer for a labile radiosensitizer. J Pharm Sci 76:384-6 |
