Characterization of primary prostate carcinoma by anti-1-amino-2-[(18)F] -fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F] FACBC) uptake

Abstract

Anti-1-amino-3-[(18)F] fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F] FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in the detection of recurrent prostate carcinoma. The aim of this study is to correlate uptake of anti-3-[(18)F] FACBC with histology of prostatectomy specimens in patients undergoing radical prostatectomy and to determine if uptake correlates to markers of tumor aggressiveness such as Gleason score. Ten patients with prostate carcinoma pre-radical prostatectomy underwent 45 minute dynamic PET-CT of the pelvis after IV injection of 347.8 ± 81.4 MBq anti-3-[(18)F] FACBC. Each prostate was co-registered to a separately acquired MR, divided into 12 sextants, and analyzed visually for abnormal focal uptake at 4, 16, 28, and 40 min post-injection by a single reader blinded to histology. SUVmax per sextant and total sextant activity (TSA) was also calculated. Histology and Gleason scores were similarly recorded by a urologic pathologist blinded to imaging. Imaging and histologic analysis were then compared. In addition, 3 representative sextants from each prostate were chosen based on highest, lowest and median SUVmax for immunohistochemical (IHC) analysis of Ki67, synaptophysin, P504s, chromogranin A, P53, androgen receptor, and prostein. 79 sextants had malignancy and 41 were benign. Highest combined sensitivity and specificity was at 28 min by visual analysis; 81.3% and 50.0% respectively. SUVmax was significantly higher (p<0.05) for malignant sextants (5.1±2.6 at 4 min; 4.5±1.6 at 16 min; 4.0±1.3 at 28 min; 3.8±1.0 at 40 min) compared to non-malignant sextants (4.0±1.9 at 4 min; 3.5±0.8 at 16 min; 3.4±0.9 at 28 min; 3.3±0.9 at 40 min), though there was overlap of activity between malignant and non-malignant sextants. SUVmax also significantly correlated (p<0.05) with Gleason score at all time points (r=0.28 at 4 min; r=0.42 at 16 min; r=0.46 at 28 min; r=0.48 at 40 min). There was no significant correlation of anti-3-[(18)F] FACBC SUVmax with Ki-67 or other IHC markers. Since there was no distinct separation between malignant and non-malignant sextants or between Gleason score levels, we believe that anti-3-[(18)F] FACBC PET should not be used alone for radiation therapy planning but may be useful to guide biopsy to the most aggressive lesion.

Keywords: Positron emission tomography (PET); anti-3-[18F] FACBC; prostate carcinoma.

Figure 1

MR (A), anti-3-[¹⁸F] FACBC PET acquired at 28 min post radiotracer administration (B), coregistered PET-MR (C) and histology (D). In this patient uptake in the right anterior and posterior mid sextants correlate with presence of tumor while a small tumor focus in the left anterior sextant is not visualized. On the histology, solid blue represent Gleason 4, solid red represents Gleason 5, and yellow represents BPH.

Figure 2

MR (A), anti-3-[¹⁸F] FACBC PET acquired at 28 min post radiotracer administration (B), coregistered PET-MR(C) and histology (D).In this patient uptake in the right anterior and posterior and left anterior basal sextants correlatewith presence of tumor but uptake in the left posterior sextant seems to correlate with inflammation. On thehistology, solid black represent Gleason 3, solid blue represents Gleason 4, dotted green represents inflammation,and yellow represents BPH.

Figure 3

Correlation of anti-3-[¹⁸F] FACBC SUV max at (A) 4 min, (B) 16 min, (C) 28min, and (D) 40 min with Gleason score.