Vanderbilt University Medical Center Nashville United States
The goals of the proposed studies are to develop, optimize and use imaging methods to non-invasively assess the temporal relationship prostate cancer growth, androgen receptor AR levels, hypoxia, and translocator protein TSPO levels. As described in the statement of work, the first year of this award focused on implementation and optimization of the imaging methods in the Pten p53 double null mutant mouse model. Towards that end, we have systematically optimized and characterized protocols for imaging tumor morphology using MRI, AR levels using 18F-fluoro-5alpha-dihydrotestosterone FDHT, hypoxia using, 18F-fluoromisonidazole, and TSPO using an in-house tracer called VUIIS-1008. The major finding of this work is the validation of TSPO as a highly sensitive and specific marker of prostate cancer with favorable imaging characteristics e.g. low bladder uptake that enable robust detection of small prostate cancers. In contrast, high background and variable uptake of FDHT and FMISO confounded the reliable evaluation of AR and hypoxia in the Ptenp53 mouse model. The observed high uptake of TSPO justifies its further evaluation in both preclinical and clinical studies as a novel biomarker for prostate cancer detection and treatment response.