In Vivo Distribution of Avidin-Conjugated MX35 and 211At-Labeled, Biotinylated Poly-L-Lysine for Pretargeted Intraperitoneal α-Radioimmunotherapy

Purpose: Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211-labeled, biotinylated, succinylated poly-l-lysine (At-211-B-PLsuc) were administered in mice to assess potential efficacy as an intraperitoneal (i.p.) therapy for microscopic tumors. We aimed to establish a timeline for pretargeted radio-immunotherapy using these substances, and estimate the maximum tolerable activity. Methods: I-125-avidin-MX35 and At-211-B-PLsuc were administered i.p. in nude mice. Tissue distributions were studied at various time points and mean absorbed doses were estimated from organ uptake of At-211-B-PLsuc. Studies of myelotoxicity were performed after administration of different activities of At-211-B-PLsuc. Results: We observed low blood content of both I-125-avidin-MX35 and At-211-B-PLsuc, indicating fast clearance. After sodium perchlorate blocking, the highest At-211 uptake was found in kidneys. Red bone marrow (RBM) accumulated some At-211 activity. Mean absorbed doses of special interest were 2.3 Gy/MBq for kidneys, 0.4 Gy/MBq for blood, and 0.9 Gy/MBq for RBM. An absorbed dose of 0.9 Gy to the RBM was found to be safe. These values suggested that RBM would be the key dose-limiting organ in the proposed pretargeting scheme, and that blood data alone was not sufficient for predicting its absorbed dose. Conclusions: To attain a favorable distribution of activity and avoid major toxicities, at least 1.0MBq of At-211-B-PLsuc can be administered 24 hours after an i.p. injection of avidin-MX35. These results provide a basis for future i.p. therapy studies in mice of microscopic ovarian cancer.