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

Abstract

Purpose:

Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211–labeled, biotinylated, succinylated poly-l-lysine (²¹¹At-B-PL_suc) 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 radioimmunotherapy using these substances, and estimate the maximum tolerable activity.

Methods:

¹²⁵I-avidin-MX35 and ²¹¹At-B-PL_suc 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 ²¹¹At-B-PL_suc. Studies of myelotoxicity were performed after administration of different activities of ²¹¹At-B-PL_suc.

Results:

We observed low blood content of both ¹²⁵I-avidin-MX35 and ²¹¹At-B-PL_suc, indicating fast clearance. After sodium perchlorate blocking, the highest ²¹¹At uptake was found in kidneys. Red bone marrow (RBM) accumulated some ²¹¹At 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 1.0 MBq of ²¹¹At-B-PL_suc 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.