Abstract
1730
Objectives Prostate Stem Cell Antigen (PSCA) is a GPI-linked cell surface glycoprotein with limited expression in normal tissue and prostate but is over-expressed in >90% of localized prostate cancer and highly over-expressed in >97% of prostate cancer bone metastases. Here we compare immunoPET imaging with the anti-PSCA A11 minibody to F-18 NaF bone scans in a 22rv1xPSCA intratibial model.
Methods 22rv1 cells were transfected with PSCA and/or FLuc. Xenografts were implanted by injecting either ~105 22rv1 or ~105 22rv1xPSCA cells into the intratibial metaphysis of male nude mice with a contralateral sham injection. 6 weeks post-implantation mice were imaged optically by injection of D-luciferin and underwent F-18 NaF microPET bone scans. Immediately following bone scans the mice were injected with ~100µCi of I-124 labeled A11 minibody (Specific activity=5.4µCi/µg, Immunoreactivity=65-82%) and imaged by microPET/CT at 24 and 48 hours.
Results F-18 NaF bone scans show increased uptake in mice bearing both 22rv1 and 22rv1xPSCA xenografts, although signal in the knee joints can make detection and quantification problematic. A11 minibody immunoPET imaging at 44hrs shows high activity solely in tibias bearing 22rv1xPSCA tumors. On biodistribution, tibias injected with 22rv1xPSCA xenografts show increased uptake (3.31%ID/g) compared to tibias injected with 22rv1 cells (0.45±0.11%ID/g) and contralateral sham injections (0.07±0.004 %ID/g).
Conclusions Intratibial xenografts of 22rv1xPSCA cells imaged at 6 weeks show increased uptake in both F-18 NaF bone scans and I-124 A11 immunoPET compared to the contralateral sham injection. However, unlike the NaF bone scans, the A11 antiPSCA minibody immunoPET signal is specific for PSCA-expressing prostate cancer with minimal background in other tissues.
Research Support UCLA Prostate Cancer SPORE Department of Defense W81WXH-08-1-0442 UCLA-Caltech Medical Scientist Training Progra