Auger radiopharmaceutical therapy targeting prostate-specific membrane antigen in a micrometastatic model of prostate cancer
Colette J. Shen, Il Minn, Robert F. Hobbs, Ying Chen, Anders Josefsson, Mary Brummet, Sangeeta Ray Banerjee, Cory Brayton, Ronnie C. Mease, Martin G. Pomper, Ana P. Kiess
Abstract
Auger radiopharmaceutical therapy is a promising strategy for micrometastatic disease given high linear energy transfer and short range in tissues, potentially limiting normal tissue toxicities. We previously demonstrated anti-tumor efficacy of a small-molecule Auger electron emitter targeting the prostate-specific membrane antigen (PSMA), 2-[3-[1-carboxy-5-(4-[ 125 I]iodo-benzoylamino)pentyl]-ureido]-pentanedioic acid), or 125 I-DCIBzL, in a mouse xenograft model. Here, we investigated the therapeutic efficacy, long-term toxicity, and biodistribution of 125 I-DCIBzL in a micrometastatic model of prostate cancer (PC). Methods: To test the therapeutic efficacy of 125 I-DCIBzL in micrometastatic PC, we used a murine model of human metastatic PC in which PSMA+ PC3-ML cells expressing firefly luciferase were injected intravenously in NSG mice to form micrometastatic deposits. One week later, 0, 0.37, 1.85, 3.7, 18.5, 37, or 111 MBq of 125 I-DCIBzL was administered (intravenously). Metastatic tumor burden was assessed using bioluminescence imaging (BLI). Long-term toxicity was evaluated via serial weights and urinalysis of non-tumor-bearing mice over a 12-month period, as well as final necropsy.