RT Journal Article SR Electronic T1 Preclinical Evaluation of 11C-Sarcosine as a Substrate of Proton-Coupled Amino Acid Transporters and First Human Application in Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1216 OP 1223 DO 10.2967/jnumed.116.173179 VO 58 IS 8 A1 Morand Piert A1 Xia Shao A1 David Raffel A1 Mathew S. Davenport A1 Jeffrey Montgomery A1 Lakshmi Priya Kunju A1 Brian G. Hockley A1 Javed Siddiqui A1 Peter J.H. Scott A1 Arul M. Chinnaiyan A1 Thekkelnaycke Rajendiran YR 2017 UL http://jnm.snmjournals.org/content/58/8/1216.abstract AB 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.