Evaluation of the biodistribution of [99mTc]Tc-PSMA-GCK01 SPECT/CT in a prospective, intraindividual comparison with [68Ga]PSMA-11 PET/CT for phenotyping in mCRPC prior to PSMA-targeted radioligand therapy

Abstract

<title>Abstract</title> Background PSMA-PET/CT became an important means for prostate cancer management. The high-resolution and signal-to-noise ratio of PET is mandatory in primary staging or biochemical relapse that often present with tiny lesions. PSMA-PET is also used to select patients for PSMA-targeted radioligand-therapy, but scanner availability increasingly becomes a bottleneck. The resolution of PSMA-SPECT/CT might be sufficient to tailor PSMA positive vs. negative disease and would help overcome supply limitations. This prospective, monocentric study evaluates the biodistribution and tumor uptake of [ ^99m Tc]Tc-PSMA-GCK01 in an intra-individual head-to-head comparison with [ ⁶⁸ Ga]PSMA-11 to assess its suitability for phenotyping prior to RLT. Results A cohort of ten patients (median age, 68 y; range, 56–85 y) with advanced-stage, metastatic prostate cancer underwent both unenhanced [ ⁶⁸ Ga]PSMA-11 PET/CT and [ ^99m Tc]Tc-PSMA-GCK01 SPECT/CT scans with a mean time interval of 6 days (± 1). The tracer uptake in malignant lesions and normal organs was assessed visually and semi-quantitatively using spherical VOIs by two nuclear medicine physicians in consensus. Compared to [ ^99m Tc]Tc-PSMA-GCK01, [ ⁶⁸ Ga]PSMA-11 displayed a trend toward higher uptake in normal organs. Renal tracer uptake was significantly higher with [ ⁶⁸ Ga]PSMA-11 than with [ ^99m Tc]Tc-PSMA-GCK01. In the salivary glands and liver, there was no statistically significant difference in uptake between the two tracers, although [ ^99m Tc]Tc-PSMA-GCK01 displayed a trend toward lower uptake. Conclusion Our study demonstrates intraindividual comparability of [ ^99m Tc]Tc-PSMA-GCK01 and [ ⁶⁸ Ga]PSMA-11 with respect to normal-organ distribution including typical reference organs such as the liver or salivary glands. If only lesions &gt; 2 cm are considered, [ ^99m Tc]Tc-PSMA-GCK01 PSMA-SPECT is a viable, cost-effective alternative to [ ⁶⁸ Ga]PSMA-11 to stratify patients toward or against PSMA-RLT.