Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography, histopathology and immunohistochemistry in primary prostate cancer

Abstract Background Targeting prostate-specific membrane antigen (PSMA) has been highly successful for imaging and treatment of prostate cancer. However, heterogeneity in immunohistochemistry indicates limitations in the effect of imaging and radionuclide therapy of multifocal disease. 99mTc-PSMA-I&S is a γ-emitting probe, which can be used for intraoperative lesion detection and postsurgical autoradiography (ARG). We aimed to study its intraprostatic distribution and compared it with (immuno)-histopathology.Results Seventeen patients who underwent RGS between 11/2018 and 01/2020 with a total of 4660 grids were included in the preliminary analysis. Marked intratumor and intrapatient heterogeneity of PSMA expression was detected, and PSMA negative foci were observed in all samples (100%). Heterogeneous intrapatient PSMA-ligand uptake was observed, and no significant correlation was present between the degree of heterogeneity of PSMA expression and PSMA-ligand uptake. Higher PSMA-ligand uptake was observed in GS ≥ 8 than GS < 8 (p < 0.001). The appearance of GP 4 was strongly associated with higher uptake (coefficient: 0.43, p < 0.001), while GP 5 also affected the uptake (coefficient: 0.07, p < 0.001).Conclusion PSMA expression and PSMA-ligand uptake show marked heterogeneity. Prostate carcinoma with GP 4 showed significantly higher uptake compared with non-neoplastic prostate tissue. Our analyses extend the scope of applications of radiolabeled PSMA-ligands to ARG for identifying high-grade disease and using its signal as a noninvasive biomarker in prostate cancer.