123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy.

Overview

abstract

UNLABELLED: Because traditional endpoints in oncology trials are not always applicable for metastatic prostate cancer, better ways of following response to treatment are needed. Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in normal human prostate epithelium and is upregulated in prostate cancer. (S)-2-(3-((S)-1-carboxy-5-((4-(123)I-iodobenzyl)amino)pentyl)ureido)pentanedioic acid, (123)I-MIP-1072, targets PSMA and was evaluated for monitoring the growth of PSMA-positive LNCaP cells in vitro and as xenografts after paclitaxel therapy. METHODS: LNCaP and 22Rv1 cells were treated with paclitaxel (0-100 nM) for 48 h, after which binding of (123)I-MIP-1072 was examined. Cell number was determined by MTS assay, and PSMA expression was analyzed by Western blotting. LNCaP xenograft-bearing mice were treated with paclitaxel (6.25 mg/kg) for 3.5 cycles of 5 d on and 2 d off. Tissue distribution of (123)I-MIP-1072 was determined on days 2 and 23 from the start of paclitaxel treatment. RESULTS: Paclitaxel (10-100 nM) inhibited LNCaP and 22Rv1 cell growth after 48 h, and binding of (123)I-MIP-1072 was proportional to cell number. Western blot analysis verified there was no paclitaxel-dependent change in PSMA expression. Treatment of LNCaP xenografts with paclitaxel resulted in a decrease in tumor volume (-21%), compared with an increase in the untreated xenografts (+205%) by day 23. Tumor uptake of (123)I-MIP-1072 was proportional to changes in tumor mass: decreased by paclitaxel treatment and increased in untreated mice. CONCLUSION: Treatment of LNCaP cells or xenograft tumors with paclitaxel resulted in growth inhibition, which was detected with (123)I-MIP-1072. The high specificity of (123)I-MIP-1072 for prostate cancer may allow monitoring of tumor progression in patients before, during, and after chemotherapy.