Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Trans-1-amino-3-18 F-fluorocyclobutanecarboxylic acid (anti-18 F-FACBC) is an amino acid PET tracer that has shown promise for visualizing prostate cancer. Therefore, we aimed to clarify the anti-18 F-FACBC transport mechanism in prostate cancer cells. We also studied the fate of anti-18 F-FACBC after it is transported into cells. Methods: For convenience, because of their longer half-lives, 14 C compounds were used instead of 18 F-labeled tracers. Trans-1-amino-3-fluoro-1-14 C-cyclobutanecarboxylic acid ( 14 C-FACBC) uptake was examined in human prostate cancer DU145 cells with the following substrates of amino acid transporters: a-(methylamino) isobutyric acid (a system A-specific substrate) and 2-amino-2-norbornanecarboxylic acid (a system L-specific substrate). The messenger RNA expression of amino acid transporters in human prostate cancer specimens was analyzed by complementary DNA microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Gene expression in DU145 cells was analyzed by qRT-PCR. We also examined the knockdown effect of the amino acid transporters system ASC transporter 2 (ASCT2) and sodium-coupled neutral amino acid transporter 2 (SNAT2) on 14 C-FACBC uptake. In addition, the possibility of 14 C-FACBC incorporation into proteins was examined. Results: 14 C-FACBC uptake by DU145 cells was markedly decreased to approximately 20% in the absence of Na 1 , compared with that in its presence, indicating that Na 1 -dependent transporters are mainly responsible for the uptake of this tracer. Moreover, 2-amino-2-norbornanecarboxylic acid inhibited the transport of 14 C-FACBC to the basal level in Na 1 -free buffer. In contrast, a-(methylamino) isobutyric acid did not inhibit 14 C-FACBC accumulation in DU145 cells. Human prostate tumor specimens and DU145 cells had similar messenger RNA expression patterns of amino acid transporter genes. Although SNAT2 and ASCT2 are 2 major amino acid transporters expressed in prostate tumor tissues and DU145 cells, ASCT2 knockdown using small interfering RNA was more effective in lowering 14 C-FACBC transport than SNAT2. Almost all intracellular 14 C-FACBC was recovered from the nonprotein fraction. Conclusion: ASCT2, which is a Na 1 -dependent amino acid transporter, and to a lesser extent Na 1 -independent transporters play a role in the uptake of 14 C-FACBC by DU145 cells. Among the Na 1 -independent transporters, system L transporters are also involved in the transport of 14 C-FACBC. Moreover, 14 C-FACBC is not incorporated into proteins in cells. These findings suggest a possible mechanism of anti-18 F-FACBC PET for prostate cancer.

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The low anti-[(18)F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[(18)F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).

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