Intra-individual comparison of ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL normal-organ biodistribution

Purpose: Detailed data comparing the biodistribution of PSMA radioligands is still scarce, raising concerns regarding the comparability of different compounds. We investigated differences in normal-organ biodistribution and uptake variability between the two most commonly PSMA tracers in clinical use, ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL.

Methods: This retrospective analysis included 34 patients with low tumor burden referred for PET/CT imaging with ⁶⁸Ga-PSMA-11 and subsequently ¹⁸F-DCFPyL. Images were acquired with 4 cross-calibrated PET/CT systems. Volumes of interest were placed on major salivary and lacrimal glands, liver, spleen, duodenum, kidneys, bladder, blood-pool and muscle. Normal-organ biodistribution of both tracers was then quantified as SUV_peak and compared using paired tests, linear regression and Bland-Altman analysis. Between-patient variability was also assessed. Clinical and protocol variables were investigated for possible interference.

Results: For both tracers the highest uptake was found in the kidneys and bladder and low background activity was noted across all scans. In the quantitative analysis there was significantly higher uptake of ⁶⁸Ga-PSMA-11 in the kidneys, spleen and major salivary glands (p < 0.001), while the liver exhibited slightly higher ¹⁸F-DCFPyL uptake (p = 0.001, mean bias 0.79 ± 1.30). The lowest solid-organ uptake variability was found in the liver (COV 21.9% for ⁶⁸Ga-PSMA-11, 22.5% for ¹⁸F-DCFPyL). There was a weak correlation between ¹⁸F-DCFPyL uptake time and liver SUV_peak (r = 0.488, p = 0.003) and, accordingly, patients scanned at later time-points had a larger mean bias between the two tracers' liver uptake values (0.05 vs 1.46, p = 0.001).

Conclusion: Normal tissue biodistribution patterns of ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyL were similar, despite subtle differences in quantitative values. Liver uptake showed an acceptable intra-patient agreement and low inter-patient variability between the two tracers, allowing its use as a reference organ for thresholding scans in the qualitative comparison of PSMA expression using these different tracers.