Synthesis, Preclinical Characterizations and Imaging Studies of [¹⁸F]AlF‐Labeled NY104, a CAIX‐Targeting Diagnostic Agent

The protein carbonic anhydrase IX (CAIX) is highly expressed in clear cell renal cell carcinoma (ccRCC), and its restrictive expression in healthy tissues makes CAIX an attractive diagnostic target. The purpose of this study was to synthesize and evaluate [¹⁸F]AlF-NY104, a small-molecule CAIX-targeting PET agent in a preclinical ccRCC model. The radiolabeling parameters for [¹⁸F]AlF-NY104 have been optimized, including the solvent volume and reaction temperature. The high-purity product was synthesized by using an automated multifunctional module Mortenon M1, leading to nondecay-corrected radiochemical yields over 50% (n = 3). [¹⁸F]AlF-NY104 showed excellent tumor targeting capability and afforded high-quality microPET/CT imaging in the OS-RC-2 tumor model (15.01 ± 0.76 %ID/g [mean ± SEM]). The radiation exposure from [¹⁸F]AlF-NY104 is estimated to be 4.44 mSv for adult male and female human subjects, which is well below the FDA recommended whole-body single exposure limit of 30 mSv. Our investigation revealed that [¹⁸F]AlF-NY104 can be conveniently and efficiently radiolabeled by using an automated module. [¹⁸F]AlF-NY104 exhibited many outstanding properties, such as rapid uptake in tumor, rapid clearance through the kidney, and low uptake in most normal organs. Moreover, the high accumulation of [¹⁸F]AlF-NY104 in tumors in CAIX-positive models offers an alternative diagnostic strategy for patients with ccRCC.