Sarcosine is a known substrate of
proton-coupled
amino acid transporters (PATs), which are overexpressed in selected tissues and solid
tumors.
Sarcosine, an N-methyl derivative of the
amino acid glycine and a metabolic product of
choline, plays an important role for
prostate cancer aggressiveness and progression. Methods:11C-radiolabeled
sarcosine was tested as a new PET imaging probe in comparison with 11C-choline in 2
prostate cancer tumor xenograft models (DU-145 and PC-3). We characterized 11C-sarcosine transport in PC-3 and LNCaP
tumor cells and performed 11C-sarcosine PET with CT in the first human subject with localized Gleason 4 + 3
prostate cancer. Target metabolite analyses of
sarcosine and its natural precursors,
glycine and
choline, were performed from independent human prostate tissues. Results: In vitro assays indicated blockage of 11C-sarcosine uptake into PC-3 and LNCaP
tumor cells by excess unlabeled (cold)
sarcosine. 5-hydroxy-l-tryptophan, but not 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic
acid, competitively inhibited 11C-sarcosine
tumor cell uptake, confirming PAT-mediated transport. In vivo
tumor-to-background ratios (TBRs) obtained from 11C-sarcosine PET were significantly elevated compared with 11C-choline in DU-145 (TBR: 1.92 ± 0.11 for 11C-
sarcosine vs. 1.41 ± 0.13 for 11C-
choline [n = 10; P < 0.002]) and PC-3
tumors (TBR: 1.89 ± 0.2 for 11C-
sarcosine vs. 1.34 ± 0.16 for 11C-
choline [n = 7; P < 0.002]). 11C-sarcosine produced high-contrast images in 1 case of localized clinically significant
prostate cancer. Target metabolite analyses revealed significant stepwise increases of
sarcosine,
glycine, and
choline tissue levels from benign prostate tissue to localized
prostate cancer and subsequently metastatic disease. 11C-sarcosine showed a favorable radiation dosimetry with an effective dose estimate of 0.0045 mSv/MBq, resulting in 2.68 mSv for a human subject (600-MBq dose). Conclusion:11C-
sarcosine is a novel radiotracer for PATs and shows initial utility for
prostate cancer imaging, with potential benefit over commonly used 11C-choline.