Healthy Tissue Uptake of 68Ga-Prostate-Specific Membrane Antigen, 18F-DCFPyL, 18F-Fluoromethylcholine, and 18F-Dihydrotestosterone

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include Ga-68-prostate-specific membrane antigen HBED-CC (Ga-68-PSMA), F-18-DCFPyL, F-18-fluoromethylcholine (F-18-FCH), and F-18-dihydrotestosterone (F-18-FDHT). Knowledge on the variability of tracer uptake in healthy tissues is important for accurate PET interpretation, because malignancy is suspected only if the uptake of a lesion contrasts with its background. Therefore, the aim of this study was to quantify uptake variability of PCa tracers in healthy tissues and identify stable reference regions for PET interpretation. Methods: A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 Ga-68-PSMA scans, 50 F-18-DCFPyL scans, 68 F-18-FCH scans, and 27 F-18-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUVmax, SUVmean, SUVpeak). Variability in uptake between patients was analyzed using the coefficient of variation (COV%). For all tracers, SUV reference ranges (95th percentiles) were calculated, which could be applicable as image-based quality control for future PET acquisitions. Results: For Ga-68-PSMA, the lowest uptake variability was observed in the blood pool (COV, 19.9%), which was significantly more stable than all other tissues (COV, 29.8%-35.2%; P = 0.001-0.024). For F-18-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; P = 0.001-0.003). The least variable F-18-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; P = 0.001-0.012). For F-18-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; P = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). Conclusion: In this multicenter analysis, healthy tissues with limited uptake variability were identified, which may serve as reference regions for PCa PET interpretation. These reference regions include the blood pool for Ga-68-PSMA and F-18-DCFPyL and the liver for F-18-FCH and F-18-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.