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001028499 1001_ $$0P:(DE-HGF)0$$aMamlins, Eduards$$b0$$eCorresponding author
001028499 245__ $$aThe Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer
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001028499 520__ $$aPURPOSE: 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.
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001028499 7001_ $$0P:(DE-Juel1)185030$$aScharbert, Lara$$b1
001028499 7001_ $$0P:(DE-Juel1)131814$$aCardinale, Jens$$b2
001028499 7001_ $$0P:(DE-HGF)0$$aKrotov, Maria$$b3
001028499 7001_ $$0P:(DE-HGF)0$$aWinter, Erik$$b4
001028499 7001_ $$0P:(DE-HGF)0$$aRathke, Hendrik$$b5
001028499 7001_ $$0P:(DE-Juel1)132024$$aStrodel, Birgit$$b6
001028499 7001_ $$0P:(DE-HGF)0$$aAnkrah, Alfred O.$$b7
001028499 7001_ $$0P:(DE-HGF)0$$aSathekge, Mike$$b8
001028499 7001_ $$0P:(DE-HGF)0$$aHaberkorn, Uwe$$b9
001028499 7001_ $$0P:(DE-HGF)0$$aKratochwil, Clemens$$b10
001028499 7001_ $$0P:(DE-HGF)0$$aGiesel, Frederik L.$$b11
001028499 773__ $$0PERI:(DE-600)2079211-6$$a10.1007/s11307-023-01881-y$$gVol. 26, no. 1, p. 81 - 89$$n1$$p81 - 89$$tMolecular imaging & biology$$v26$$x1536-1632$$y2024
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