Mamlins, Eduards; Scharbert, Lara; Cardinale, Jens; Krotov, Maria; Winter, Erik; Rathke, Hendrik; Strodel, Birgit; Ankrah, Alfred O; Sathekge, Mike; Haberkorn, Uwe; Kratochwil, Clemens; Giesel, Frederik L (2024). The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer. Molecular imaging and biology, 26(1), pp. 81-89. Springer-Verlag 10.1007/s11307-023-01881-y
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PURPOSE
Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu 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 99mTc or therapeutically with 188Re 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 [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]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 [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]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 [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]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 [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine |
UniBE Contributor: |
Rathke, Hendrik Gabriel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1536-1632 |
Publisher: |
Springer-Verlag |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
12 Dec 2023 12:45 |
Last Modified: |
01 Feb 2024 00:15 |
Publisher DOI: |
10.1007/s11307-023-01881-y |
PubMed ID: |
38066252 |
Uncontrolled Keywords: |
PSMA-GCK01 Prostate cancer SPECT Technetium-99 m Theranostic |
BORIS DOI: |
10.48350/190089 |
URI: |
https://boris.unibe.ch/id/eprint/190089 |
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