PT  - JOURNAL ARTICLE
AU  - Hillier, Shawn M.
AU  - Kern, Ashley M.
AU  - Maresca, Kevin P.
AU  - Marquis, John C.
AU  - Eckelman, William C.
AU  - Joyal, John L.
AU  - Babich, John W.
TI  - <sup>123</sup>I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy
AID  - 10.2967/jnumed.110.086751
DP  - 2011 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1087--1093
VI  - 52
IP  - 7
4099  - http://jnm.snmjournals.org/content/52/7/1087.short
4100  - http://jnm.snmjournals.org/content/52/7/1087.full
SO  - J Nucl Med2011 Jul 01; 52
AB  - 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.