The Impact of Peptide Amount on Tumor Uptake to Assess PSMA Receptor Saturation on⁶⁸Ga-PSMA-11 PET/CT in Patients with Primary Prostate Cancer

Abstract

<b>Rationale: </b> Gallium-68 (⁶⁸Ga)-labelled Prostate-specific Membrane Antigen (PSMA) is often produced on-site, where usually a fixed amount of peptide is conjugated to the generator-eluate. However, fluctuations in specific activity might influence tracer distribution and tumor accumulation. Therefore, our aim was to investigate the potential effect of varying administered peptide amount on ⁶⁸Ga-PSMA-11 uptake in tumor lesions using PET/CT in patients with primary prostate cancer (PCa). Additionally, the impact of tumor lesion volume on this potential effect and on accumulation in reference organs was assessed. <b>Methods:</b> Imaging data of 362 men with primary PCa who received ⁶⁸Ga-PSMA-11 PET/CT were retrospectively included. Scan quantification was performed for normal tissue and primary tumor lesions. Patients were divided into three groups based on their tumor lesion volume. Correlation and (multivariable) linear regression analyses were performed. <b>Results:</b> Median index lesion volume was 9.50 mL (range 0.064–174 mL). Groups were based on quartiles of prostatic lesion volume: ≤4.11 mL (group 1), 4.11–20.6 mL (group 2), and ≥20.6 mL (group 3). No correlation was found between administered peptide amount and tumor uptake (SUVpeak or SUVmean) for all groups, except for a significant correlation for SUVmean in the first group (<i>P</i> = 0.008). Linear regression analysis supported these findings. <b>Conclusion:</b> No evident effect was observed of administered peptide amount on ⁶⁸Ga-PSMA-11 uptake in tumor lesions, except for a significant positive correlation between administered peptide amount and tumor SUVmean for group 1. Findings imply that no receptor saturation occurs in men with primary PCa at peptide levels of ~2.5 µg.

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