Quantification of the serial A11 immunoPET scans shows an overall increase in tibial uptake of the A11 minibody in the tumor bearing tibia across all time points (p 0.0001, two-way ANOVA), with an increase in the positive tibia over time (p=0.001). subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect which may help evaluate the clinical response to androgen deprivation and the development (-)-BAY-1251152 of castration resistance. could lead to improved therapeutic strategies and could allow for targeted radiation therapy or a more prompt transition to option androgen deprivation brokers or systemic chemotherapy in the patients whose tumors reactivate the androgen-signaling axis. Prostate stem cell antigen (-)-BAY-1251152 (PSCA) is usually highly expressed in 83C100% of prostate cancers and overexpressed in the great majority of prostate cancer bone metastases (87C100%) and in many metastases to other sites (67% liver, 67C95% lymph node) (18C21). Its expression correlates with the Gleason score, tumor invasion, androgen independence, metastasis, and a poor prognosis (21C26). The PSCA promoter contains an androgen response element and PSCA expression is regulated by androgens in the normal mouse prostate (27, 28). Likewise, androgen deprivation decreases PSCA mRNA expression in human high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (29, 30). We have previously shown that immunoPET with an affinity matured 124I-labeled A11 anti-PSCA minibody, an antibody fragment with pharmacokinetics optimized for imaging, can be used for specific and quantitative imaging of PSCA expression (31C33). We therefore hypothesize that imaging PSCA expression using the A11 minibody may outperform bone scans for imaging prostate cancer bone metastases and allow for imaging changes in PSCA expression in response to androgen deprivation. In this work, we will compare the sensitivity of the A11 minibody to 18F-Fluoride bone scans for detecting bone tumors using a Rabbit Polyclonal to THOC5 naturally PSCA expressing, purely osteoblastic, LAPC-9 intratibial xenograft model. We will also investigate changes in PSCA expression in LAPC-9 subcutaneous xenografts in response to androgen deprivation with MDV-3100 and demonstrate that anti-PSCA A11 minibody immunoPET can image these changes microCT and histology Following biodistribution, tibias were stored in 10% phosphate buffered formalin until (-)-BAY-1251152 radioactivity had decayed. The tibias were then analyzed by 20m resolution microCT (CT40, SANCO Medical). Volume renderings were generated with OsirX 5.6 (39). The tibia (-)-BAY-1251152 samples were then decalcified and embedded in paraffin and sectioned for histological analysis. Only those mice with intratibial tumor establishment confirmed by gross and/or histological analysis were included in the analysis. A11 minibody imaging of response to therapy with MDV-3100 LAPC-9 s.c. xenografts were implanted bilaterally and allowed to grow for 3 weeks. The mice then received a pre-treatment A11 minibody immunoPET/CT at 44 hours post-injection as previously described, with the exception that each mouse received a dose of ~50g of 124I-A11 minibody (32). Immediately following the pre-treatment scan the mice were randomized into treatment groups and received either 40mg/kg MDV-3100 (ChemScene) or vehicle by daily gavage. The vehicle consisted of 300L of water with 1% carboxymethylcellulose (Sigma-Aldrich), 0.1% Tween-80 (Sigma-Aldrich) and 1.6% DMSO. After five days of treatment, one mouse from each group underwent a microPET/CT scan to confirm that minimal signal was retained from the first imaging injection, and then all mice were again injected with ~50g of 124I-labeled A11 minibody. Around the 7th day of treatment, 44 hours post-A11 minibody injection, the mice received a post-treatment scan following which the mice were sacrificed and biodistribution and microPET image analysis and quantification with partial volume correction were performed as previously described (32). The tumors were then fixed and examined histologically (see supplemental materials). Quantitative flow cytometry LAPC-9 s.c. xenograft bearing mice treated identically to the imaging cohorts, except without the injection of the.