Abstract
Abstract : The primary objective of this research effort is the development of noninvasive imaging method to assess branched-chain amino acid metabolism (known to be modified in prostate cancer [PC]) to distinguish malignant from healthy tissue. The approach is to use MRSI of hyperpolarized 13C-ketoisocaproic acid (KIC) to interrogate its conversion to leucine as catalyzed by branched-chain aminotransferase (BCAT). During this funding cycle, we: 1. Developed a high-throughput assay for assessing in vitro BCAT activity. 2. Demonstrated BCAT activity in TRAMP mouse models was significantly lower than that found in human PC. 3. Searched for an animal model more closely mimicking human metabolism by assessing four prostate cancer cell lines: PC-3, DU-145, LNCaP and LAPC-4. The PC-3 cells had the highest BCAT activity, although still appreciably lower than human PC. 4. Performed hyperpolarized in vivo MRS studies on PC-3 xenografts. Although the xenograph BCAT activity was 2.5 fold higher than cells alone (approaching human levels), the tumors grew very poorly (volumes 0.2 cc, as compared to the expected 1 cc) and were inadequate to yield sufficient SNR for the in vivo MRS studies. 5. Initiated additional xenografts studies as well as investigation into other PC metabolic pathways.
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