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-(18)F-fluorocyclobutane-1-carboxylic acid ((18)F-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 (18)F-FACBC PET.

Methods: Sixteen clinical trials involving 611 (18)F-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 (18)F-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 (18)F-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.

Keywords: 18F-FACBC; physiologic uptake; positron emission tomography.

FIGURE 1

(A) Early-time-point ¹⁸F-FACBC maximum-intensity-anterior projection (MIP) demonstrates intense liver and pancreatic uptake, cerebral and lung uptake less than blood pool, and absent urinary excretion. Greater muscle uptake is noted in upper body because scanning proceeded caudal to cranial, and muscle uptake increased with time. (B) MIP from different patient in dedicated head and neck study demonstrates moderate uptake in salivary glands, lymphoid tissue of Waldeyer’s ring, and pituitary activity (arrow).

FIGURE 2

Sagittal, coronal, and maximum-intensity-projection (MIP) ¹⁸F-FACBC images acquired over 3 time intervals (5–16, 17–28, and 29– 40 min) in patient with recurrent prostate cancer. Images demonstrate common appearance of background organ structures as described in text. Uptake is noted in right iliac nodes (arrows) at site of metastatic recurrent prostate carcinoma. Bladder activity initially is absent but moderately increases with time. Also noted is mild to moderate diffuse esophageal activity (arrowheads).

FIGURE 3

(A) Coregistered axial ¹⁸F-FACBC PET/CT image demonstrates focal uptake in known left breast carcinoma (arrow), but uptake in breast tissue is less than blood pool. (B) Coregistered sagittal ¹⁸F-FACBC PET/CT image shows focal uptake in tubulovillous adenoma (arrow) with atypia, a premalignant tumor, detected incidentally on ¹⁸F-FACBC.

FIGURE 4

(A) Coregistered axial ¹⁸F-FACBC PET/CT image from summed dynamic ¹⁸F-FACBC renal study demonstrates lack of uptake in MR imaging–proven hepatic hemangioma (small arrow) and left renal cyst (large arrow). (B) Coregistered axial ¹⁸F-FACBC PET/CT image demonstrates uptake in renal cancer (arrow) similar to that of renal parenchyma on summed dynamic images.

FIGURE 5

(A) Coregistered sagittal ¹⁸F-FACBC PET/CT image in patient with prostate bed recurrence postprostatectomy. There is mild uptake in urethra (arrowheads) but more focally intense uptake at base of bladder above expected course of urethra in biopsy-proven recurrence (arrow). In addition, uptake is shown in coregistered axial ¹⁸F-FACBC PET/CT image for clinically proven prostatitis in healthy volunteer (B) and in patient with benign prostatic hyperplasia (C).

FIGURE 6

Nonmalignant ¹⁸F-FACBC uptake in coregistered coronal PET/CT image of meningioma proven on MR imaging (arrow) (A), coregistered axial PET/CT image of inflammatory skin papule (arrow) in patient with recurrent prostate cancer (B), coregistered coronal PET/CT image of symmetric inguinal nodes in ringworm infestation as well as physiologic bowel activity (C), and osteoid osteoma on coregistered axial PET/CT image (D).