Preliminary studies using At-211-labeled anti-PSMA MAb for treatment of metastatic prostate cancer in a mouse model

Objectives The objective of the research was to demonstrate that PSA levels can be reduced in a mouse model for prostate cancer skeletal metastases after treatment with an ²¹¹At-labeled anti-PSMA monoclonal antibody (MAb).

Methods Four groups of 18 SCID mice were implanted with C4-2B human prostate cancer cells into the tibia. MAbs (107-1A4 & MOPC-21) were modified with maleimide-closo-decaborate(2-) for labeling with ²¹¹At. Blood was monitored weekly for PSA levels (n=13/group). Five remaining mice per group had blood draws weekly to evaluate CBC, liver enzymes, bilirubin, urea and creatinine. The study used 4 MAb (10 μg each) treatment groups. Grp 1: unmodified anti-PSMA MAb, 107-1A4; Grp 2: non-specific MAb, MOPC-21 labeled with 10 μCi ²¹¹At; Grp 3: 107-1A4, 10 μCi ²¹¹At; and Grp 4: 107-1A4, 1 μCi ²¹¹At.

Results All groups had a large variation in PSA values. The specific MAb, [²¹¹At]107-1A4 (10 μCi/10 μg), had the lowest avg PSA values, with the avg PSA values in other groups being: Grp2<Grp4~Grp1. When the PSA values were evaluated relative to the initial PSA value, the avg values (± std dev) were: Grp 1: 7.9±10x; Grp 2: 3.6±3.5x; Grp 3: 2.0±1.5x; and Grp 4: 6.1±4.3x. No toxicity was noted from the treatment by blood analyses.

Conclusions Treatment with 10 μCi ²¹¹At-labeled 107-1A4 dramatically decreased average blood PSA values without toxicity.

Research Support These studies were funded by the Pacific NW Prostate Cancer SPORE (P50-CA97186) and the Fred Hutchinson Cancer Research Center.