Journal of Nuclear Medicine | |
123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy | |
Ashley M. Kern1  John W. Babich1  John L. Joyal1  John C. Marquis1  Kevin P. Maresca1  Shawn M. Hillier1  William C. Eckelman1  | |
[1] Molecular Insight Pharmaceuticals, Cambridge, Massachusetts Molecular Insight Pharmaceuticals, Cambridge, Massachusetts Molecular Insight Pharmaceuticals, Cambridge, Massachusetts | |
关键词: molecular imaging; oncology; radiopharmaceuticals; prostate cancer; prostate-specific membrane antigen; | |
DOI : 10.2967/jnumed.110.086751 | |
学科分类:医学(综合) | |
来源: Society of Nuclear Medicine | |
【 摘 要 】
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.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912010198154ZK.pdf | 970KB | download |