The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [ 99m Tc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [ 99m Tc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.

Autor: Mamlins E; Department of Nuclear Medicine, Medical Faculty, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany. eduards.mamlins@med.uni-duesseldorf.de., Scharbert L; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Juelich GmbH, Juelich, Germany.; Institute of Theoretical and Computational Chemistry, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany., Cardinale J; Department of Nuclear Medicine, Medical Faculty, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany.; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Krotov M; Department of Nuclear Medicine, Medical Faculty, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany., Winter E; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Rathke H; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Department of Nuclear Medicine, University Hospital of Bern - Inselspital, Bern, Switzerland., Strodel B; Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Juelich GmbH, Juelich, Germany.; Institute of Theoretical and Computational Chemistry, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany., Ankrah AO; Korle Bu Teaching Hospital, Accra, Ghana., Sathekge M; Department of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa., Haberkorn U; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Nuclear Medicine, DKFZ, Heidelberg, Germany.; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany., Kratochwil C; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Giesel FL; Department of Nuclear Medicine, Medical Faculty, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Moorenstrasse 5, 40225, Dusseldorf, Germany.; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2024 Feb; Vol. 26 (1), pp. 81-89. Date of Electronic Publication: 2023 Dec 08.
DOI: 10.1007/s11307-023-01881-y
Abstrakt: Purpose: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [ 177 Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177 Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99m Tc or therapeutically with 188 Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [ 99m Tc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking.
Procedures: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [ 99m Tc]Tc-EDDA/HYNIC-iPSMA or [ 99m Tc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden).
Results: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [ 99m Tc]Tc-PSMA-GCK01 compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [ 99m Tc]Tc-PSMA-GCK01 vs. median 9.11 [ 99m Tc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [ 99m Tc]Tc-PSMA-GCK01 (0.83) compared to [ 99m Tc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands.
Conclusions: The novel theranostic tracer [ 99m Tc]Tc/[ 188 Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [ 99m Tc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.
(© 2023. The Author(s).)
Databáze: MEDLINE
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