Abstract
PurposeDetailed 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.MethodsThis 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 SUVpeak 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.ResultsFor 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 SUVpeak (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).ConclusionNormal 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.
Highlights
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein upregulated in most prostate cancer (PC) cells and its expression levels relate to tumor stage and grade [1,2,3]
Patients We retrospectively reviewed 43 consecutive adult male patients who had undergone Positron Emission Tomography (PET)/Computed Tomography (CT) scans with both 68Ga-PSMA-11 and 18F-DCFPyL at Peter MacCallum Cancer Centre, between October 2014 and April 2018
Visual assessment of the expected biodistribution of both tracers was considered normal for all but one patient, who had a past history of right nephrectomy prior to both scans
Summary
Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein upregulated in most prostate cancer (PC) cells and its expression levels relate to tumor stage and grade [1,2,3]. Exploiting this feature, several low-molecular-weight Glu-ureido–based PSMA inhibitor radioligands for Positron Emission Tomography/Computed. Tomography (PET/CT) have entered the clinical scope of PC workup [4,5,6] These tracers bind to the extracellular domain of PSMA and are internalized, leading to tumor uptake and retention [7, 8].
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