The new promise of FACBC position emission tomography/computed tomography in the localization of disease relapse after radical treatment for prostate cancer: are we turning to the right radiotracer?

The biochemical relapse (BCR) of prostate cancer (PCa) after radical treatment precedes the clinical disease by many years, but localizing the site of recurrence is a challenge. Positron emission tomography/computed tomography (PET/CT) with 11C- or 18F-choline is the most accurate technique in the assessment of PCa relapse [1], and it can detect the site of disease recurrence even with a very low prostate-specific antigen (PSA) level [2]. Unfortunately, choline PET/CT can detect only half of the PCa lesions because of the slow proliferation of PCa cells that reflects a slow membrane metabolism with a resulting small amount of choline uptake [3]. For this reason, some metastatic deposits >10mm may be negative at choline PET/CT scan. Fortunately, research in the field of molecular imaging never stops, and new radiotracers are now under evaluation. In recent years, a synthetic L-leucine analog (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC]) has been proposed as a possible radiotracer for PCa [4]. FACBC uptake is related to the functional activity of two different amino acid transporters, and the distribution of the tracer in the body is more favorable than choline: The uptake of FACBC in the kidney is negligible, and no activity is found in the urinary tract. Other advantages of FACBC are the short synthesis time and a long half-life, which eliminate the need for an onsite cyclotron, rendering the technique more available. Above all, the first clinical studies showed very promising and reproducible results. Improvement in the detection rate is about 20–30% in comparison with other imaging techniques, making FACBC the possible radiotracer of the future for PCa [4] and [5]. In a recent paper published in the European Journal of Nuclear Medicine and Molecular Imaging, our group compared FACBC PET/CT with 11C-choline PET/CT in 15 patients with BCR after radical prostatectomy and without androgen deprivation therapy (mean PSA level at time of enrollment: 2.1±2 ng/ml) [5]. We found better detection rates with FACBC for patient analysis (40% vs 20%) as well as lesion analysis. In particular, every lesion detected with 11C-choline was also visualized with FACBC, but FACBC found twice as many positive patients and positive lesions than 11C-choline in the bones, lymph nodes, and prostatic fossa, indicating that FACBC may be superior to 11C-choline for the identification of PCa cells. Last but not least, the images obtained with FACBC were dramatically more clear and evident than those obtained with 11C-choline, with a superior target-to-background ratio for FACBC in all lesions. We confirmed our results in a series of 50 patients with BCR after radical prostatectomy, and we will initiate a trial in the setting of preoperative nodal staging in high-risk patients. In conclusion, FACBC is emerging as a very promising tracer for the evaluation of patients with PCa, with higher sensitivity than 11C-choline and significant practical advantages. We hope to confirm these optimal results in a greater population with disease relapse and in different clinical scenarios.