A Microdosing Study with <sup>99m</sup>Tc-PHC-102 for the SPECT/CT Imaging of Primary and Metastatic Lesions in Renal Cell Carcinoma Patients
Oana C. Kulterer, Sarah Pfaff, Wolfgang Wadsak, Nathalie Garstka, Mesut Remzi, Chrysoula Vraka, Lukas Nics, Markus Mitterhauser, Franziska Bootz, Samuele Cazzamalli, Nikolaus Krall, Dario Neri, Alexander Haug
Abstract
<sup>99m</sup>Tc-PHC-102 is a <sup>99m</sup>Tc-labeled derivative of acetazolamide, a high-affinity small organic ligand of carbonic anhydrase IX (CAIX). <sup>99m</sup>Tc-PHC-102 has previously shown favorable 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 <sup>99m</sup>Tc-PHC-102 in SPECT in patients with renal cell carcinoma while also assessing the safety and tolerability of the radiotracer. <b>Methods:</b> We studied 5 patients with localized or metastatic ccRCC in a microdosing regimen, after the administration of a 50-μg total of CAIX ligand and 600–800 MBq of <sup>99m</sup>Tc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analyzed by serial SPECT/CT scans at 3 time points (30 min, 2 h, and 6 h) after intravenous administration. <b>Results:</b> In the 5 patients studied, <sup>99m</sup>Tc-PHC-102 was well tolerated and no study drug–related adverse events were recorded. In the stomach, kidneys, and gallbladder, the radiotracer showed a rapid initial uptake, which cleared over time. Localization of the study drug in primary tumors of 5 patients was observed, with favorable tumor-to-background ratios. <sup>99m</sup>Tc-PHC-102 SPECT/CT allowed the identification of 4 previously unknown lung and lymph node metastases in 2 patients. <b>Conclusion:</b><sup>99m</sup>Tc-PHC-102 is a promising SPECT tracer for the imaging of patients with ccRCC. This tracer has the potential to identify primary and metastatic lesions in different anatomic locations. <sup>99m</sup>Tc-PHC-102 might also serve as a companion diagnostic agent for future CAIX-targeting therapeutics.