In Vivo Imaging of Branched Chain Amino Acid Metabolism in Prostate Cancer.

摘要

The primary objective of this research effort was 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). We first determined that while BCAT activity is altered in prostate cancer relative to healthy tissue, insufficient enzymatic levels significantly limits the use of this biomarker for hyperpolarized 13C MR spectroscopic imaging of prostate cancer in vivo. Under a revised statement of work, we investigated hyperpolarized 13C MRS markers of prostate cancer metabolism in terms of Krebs s cycle activity (13C-diethylsuccinate) and oxidative stress (13C-cysteine and -cysteine analogs). Hyperpolarized [1,4-13C]-diethylsuccinate was found not to be a useful in vivo imaging biomarker of Krebs s cycle activity. However, [1-13C] mercaptopyruvate was determined to be a viable substrate for the in vitro assessment of oxidative stress, with in vivo studies needed to confirm and extend these findings.