Healthy Tissue Uptake of ⁶⁸Ga-Prostate Specific Membrane Antigen (PSMA), ¹⁸F-DCFPyL, ¹⁸F-Fluoromethylcholine (FCH) and ¹⁸F-Dihydrotestosterone (FDHT)

Abstract

Positron Emission Tomography (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, since 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 n = 232 PCa PET/CT scans from multiple hospitals was analyzed, including n = 87 ⁶⁸Ga-PSMA scans; n = 50 ¹⁸F-DCFPyL scans; n = 68 ¹⁸F-FCH scans and n = 27 ¹⁸F-FDHT scans. Tracer uptake was assessed in the blood pool, lung, liver, bone marrow and muscle – using several Standarized Uptake Values (SUV_max, 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 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%, P = 0.001-0.024). For ¹⁸F-DCFPyL, lowest variability was observed in the blood pool and liver (COV 14.4% and 21.7%, P = 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%, P = 0.001-0.012). For ¹⁸F-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 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.