Abstract
Sarcosine is a known substrate of proton-coupled amino acid transporters (PAT), 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: Carbon-11 radiolabeled sarcosine (11C-sarcosine) was tested as a new positron emission tomography (PET) imaging probe in comparison with 11C-choline in two 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 computed tomography (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 (HT), but not 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), competitively inhibited 11C-sarcosine tumor cell uptake, confirming PAT-mediated transport. In vivo tumor-to-background ratios (TBR) obtained from 11C-sarcosine PET were significantly elevated compared to 11C-choline in DU-145 (TBR 11C-sarcosine: 1.92 ± 0.11 vs. 1.41 ± 0.13 for 11C-choline (n = 10; P < 0.002), and PC-3 tumors (TBR 11C-sarcosine: 1.89 ± 0.2 vs. 1.34 ± 0.16 for 11C-choline (n = 7; P < 0.002). 11C-sarcosine produced high-contrast images in one case of localized clinically significant prostate cancer. Target metabolite analyses revealed significant step-wise 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 PAT transporters and shows initial utility for prostate cancer imaging, with potential benefit over commonly used 11C-choline.
- Molecular Imaging
- Oncology: GU
- Radiopharmaceuticals
- 11C-sarcosine
- PAT
- prostate cancer
- proton-coupled amino acid transporter
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.