Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology 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&...

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Main Authors: Hui Wang, Marianne Remke, Thomas Horn, Kristina Schwamborn, Yiyao Chen, Katja Steiger, Wilko Weichert, Hans-Jürgen Wester, Margret Schottelius, Wolfgang A. Weber, Matthias Eiber
Format: Article
Language:English
Published: SpringerOpen 2023-11-01
Series:EJNMMI Research
Subjects:
Online Access:https://doi.org/10.1186/s13550-023-01044-8
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author Hui Wang
Marianne Remke
Thomas Horn
Kristina Schwamborn
Yiyao Chen
Katja Steiger
Wilko Weichert
Hans-Jürgen Wester
Margret Schottelius
Wolfgang A. Weber
Matthias Eiber
author_facet Hui Wang
Marianne Remke
Thomas Horn
Kristina Schwamborn
Yiyao Chen
Katja Steiger
Wilko Weichert
Hans-Jürgen Wester
Margret Schottelius
Wolfgang A. Weber
Matthias Eiber
author_sort Hui Wang
collection DOAJ
description 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 intra-patient heterogeneity of PSMA expression was detected, and PSMA negative foci were observed in all samples (100%). Heterogeneous intra-patient 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 Gleason Pattern (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.
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spelling doaj.art-e730479a683c4bf18070e7f31822ee142023-11-20T10:53:37ZengSpringerOpenEJNMMI Research2191-219X2023-11-0113111210.1186/s13550-023-01044-8Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancerHui Wang0Marianne Remke1Thomas Horn2Kristina Schwamborn3Yiyao Chen4Katja Steiger5Wilko Weichert6Hans-Jürgen Wester7Margret Schottelius8Wolfgang A. Weber9Matthias Eiber10Department of Nuclear Medicine, West China Hospital, Sichuan UniversityInstitute of Pathology, School of Medicine, Technical University MunichDepartment of Urology, Klinikum Rechts der Isar, Technical University MunichInstitute of Pathology, School of Medicine, Technical University MunichDepartments of Mathematics and Life Sciences, Technical University MunichInstitute of Pathology, School of Medicine, Technical University MunichInstitute of Pathology, School of Medicine, Technical University MunichPharmaceutical Radiochemistry, Technical University MunichTranslational Radiopharmaceutical Sciences, Departments of Nuclear Medicine and of Oncology, Centre Hospitalier Universitaire Vaudois, University of LausanneDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University MunichDepartment of Nuclear Medicine, Klinikum Rechts der Isar, Technical University MunichAbstract 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 intra-patient heterogeneity of PSMA expression was detected, and PSMA negative foci were observed in all samples (100%). Heterogeneous intra-patient 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 Gleason Pattern (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.https://doi.org/10.1186/s13550-023-01044-8Primary prostate cancerHeterogeneity99mTc-PSMA-I&SARGImmunohistochemistry
spellingShingle Hui Wang
Marianne Remke
Thomas Horn
Kristina Schwamborn
Yiyao Chen
Katja Steiger
Wilko Weichert
Hans-Jürgen Wester
Margret Schottelius
Wolfgang A. Weber
Matthias Eiber
Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
EJNMMI Research
Primary prostate cancer
Heterogeneity
99mTc-PSMA-I&S
ARG
Immunohistochemistry
title Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
title_full Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
title_fullStr Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
title_full_unstemmed Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
title_short Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
title_sort heterogeneity of prostate specific membrane antigen psma and psma ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer
topic Primary prostate cancer
Heterogeneity
99mTc-PSMA-I&S
ARG
Immunohistochemistry
url https://doi.org/10.1186/s13550-023-01044-8
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