Anti-1-Amino-3-¹⁸F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

Abstract

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.

Molecular Imaging of Prostate Cancer

“…Some encouraging clinical reports about FACBC are found in the literature (32,33). Recently, investigators reported that FACBC PET/ CT had considerably higher accuracy and helped detect more prostatic and extraprostatic disease than indium 111 ( 111 In)−labeled capromab pendetide, an antibody directed against the internal epitope of the PSMA molecule and imaged with single photon emission computed tomography (SPECT), as discussed later in this article (34). An example of FACBC PET/MR imaging is given in Figure 7.…”

Update on 18F-Fluciclovine PET for Prostate Cancer Imaging

“…Benign and malignant bone lesions (e.g. osteoid osteoma and multiple myeloma) have reported uptake (48). Finally, single pelvic, non-focal, or non-mass-like 18F-fluciclovine activity not associated with a CT abnormality in our experience has been uncommonly seen with benign follow-up and should therefore be considered equivocal, warranting further evaluation with MR or biopsy (Fig.…”

“…Several benign conditions can demonstrate increase 18F-fluciclovine uptake leading to false-positive findings (48). Benign prostatic hypertrophy, acute and chronic inflammation (including post radiation) and infection all demonstrate varying levels of 18F-fluciclovine uptake.…”

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs

“…2). Brain parenchyma activity is minimal, and in most patients, bladder activity is absent or mild (43). Compared with 11 C-MET, 18 F-fluciclovine seems to have more rapid pancreatic clearance and comparatively lower levels of renal and bladder activity.…”

“…Industry-sponsored phase 3b trials in the United States and the United Kingdom are ongoing. In our experience, 18 F-fluciclovine PET may be most useful for the detection of small and borderline nodes in the range of 5-15 mm and for occult skeletal lesions not detected by conventional imaging, with a lower sensitivity for blastic skeletal lesions than for mixed and lytic or silent lesions (43).…”