A microdosing study with 99mTc-PHC-102 for the SPECT/CT imaging of primary and metastatic lesions in renal cell carcinoma patients.

99mTc-PHC-102 is a 99mTc-labeled derivative of acetazolamide, a high-affinity small organic ligand of Carbonic Anhydrase IX (CAIX). 99mTc-PHC-102 has previously shown favourable in vivo biodistribution properties in mouse models of CAIX-positive clear cell renal cell carcinoma (ccRCC) and colorectal cancer. In this study, we aimed to explore the targeting performance of 99mTc-PHC-102 in single-photon emission computed tomography (SPECT) in patients with RCC, while also assessing the safety and tolerability of the radiotracer. Methods: We studied five patients with localized or metastatic clear cell renal cell carcinoma (ccRCC) in a microdosing regimen, after the administration of 100 µg total CAIX ligand and 600-800 MBq 99mTc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analysed by serial SPECT/CT scans at three time points (30 minutes, 2, and 6 hours) after intravenous administration. Results: In the five patients studied, 99mTc-PHC-102 was well tolerated and no study drug-related adverse events were recorded. The radiotracer showed a rapid initial uptake in the stomach, kidneys and gallbladder, which cleared over time. Localization of the study drug in primary tumors of five patients was observed with favourable tumour-to-background ratios. 99mTc-PHC-102-SPECT/CT allowed the identification of four previously unknown lung and lymph node metastases in two patients. Conclusion:99mTc-PHC-102 is a promising SPECT tracer for the imaging of patients with clear cell renal cell carcinoma. This tracer has the potential to identify primary and metastatic lesions in different anatomical locations. 99mTc-PHC-102 might also serve as companion diagnostic agent for future CAIX-targeting therapeutics.