123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy
Open Access
- 16 June 2011
- journal article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 52 (7), 1087-1093
- https://doi.org/10.2967/jnumed.110.086751
Abstract
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-((4-123I-iodobenzyl)amino)pentyl)ureido)pentanedioic acid, 123I-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 123I-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 123I-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 123I-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 123I-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 123I-MIP-1072. The high specificity of 123I-MIP-1072 for prostate cancer may allow monitoring of tumor progression in patients before, during, and after chemotherapy.This publication has 22 references indexed in Scilit:
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