Prostate Specific Membrane Antigen

Although prostate cancer has received much attention because of the success of diagnostic biomarkers, the success of RIT for the disease has lagged behind. Studies of 131I -murine CC49 did not show objective response (87) in patients with prostate cancer. Subsequent attempts to increase antigen expression using interferon pretreatment also did not result in objective treatment responses (88). Fourteen patients received seven doses of interferon, followed by 2775 MBq/m2 (75 mCi/m2) 131I-CC49 treatment. Although antigen (TAG-72) expression seemed to be upregulated, evidenced by increased tumor localization, no significant response was achieved. The immunogenicity of the murine protein remained a problem.

Prostate-specific membrane antigen (PSMA) is a nonsecreted internalizing antigen, and therefore an excellent target for RIT. Humanized mAb J591 targets the external domain of PSMA (89). Phase 1 studies of 90Y and 177Lu labeled humanized J591 have been completed, and have shown an excellent safety profile with dose-limiting toxicity being, as expected, hematopoietic (90,91).

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