Healthy Tissue Uptake of⁶⁸Ga-Prostate-Specific Membrane Antigen,¹⁸F-DCFPyL,¹⁸F-Fluoromethylcholine, and¹⁸F-Dihydrotestosterone

PET is increasingly used for prostate cancer (PCa) diagnostics. Important PCa radiotracers include ⁶⁸Ga-prostate-specific membrane antigen HBED-CC (⁶⁸Ga-PSMA), ¹⁸F-DCFPyL, ¹⁸F-fluoromethylcholine (¹⁸F-FCH), and ¹⁸F-dihydrotestosterone (¹⁸F-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. <b>Methods:</b> A total of 232 PCa PET/CT scans from multiple hospitals was analyzed, including 87 ⁶⁸Ga-PSMA scans, 50 ¹⁸F-DCFPyL scans, 68 ¹⁸F-FCH scans, and 27 ¹⁸F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow, and muscle using several SUVs (SUV_max, SUV_mean, SUV_peak). 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. <b>Results:</b> For ⁶⁸Ga-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%; <i>P</i> = 0.001-0.024). For ¹⁸F-DCFPyL, the lowest variability was observed in the blood pool and liver (COV, 14.4% and 21.7%, respectively; <i>P</i> = 0.001-0.003). The least variable ¹⁸F-FCH uptake was observed in the liver, blood pool, and bone marrow (COV, 16.8%-24.2%; <i>P</i> = 0.001-0.012). For ¹⁸F-FDHT, low uptake variability was observed in all tissues, except the lung (COV, 14.6%-23.6%; <i>P</i> = 0.001-0.040). The different SUV types had limited effect on variability (COVs within 3 percentage points). <b>Conclusion:</b> 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 ⁶⁸Ga-PSMA and ¹⁸F-DCFPyL and the liver for ¹⁸F-FCH and ¹⁸F-FDHT. Healthy tissue SUV reference ranges are presented and applicable as image-based quality control.