66Ga: A Novelty or a Valuable Preclinical Screening Tool for the Design of Targeted Radiopharmaceuticals?

Emerging interest in extending the plasma half-life of small molecule radioligands warrants a consideration of the appropriate radionuclide for PET imaging at longer time points (> 8 h). Among candidate positron-emitting radionuclides, Ga-66 (t(1/2) = 9.5 h, beta+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of Ga-66 to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. Ga-66 was produced by irradiation of a Zn-nat target. Ga-66(3+) ions were separated from Zn2+ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn2+ ions and allowed 90.2 +/- 2.8% recovery of Ga-66(3+). Three ligands were radiolabeled in 46.4 +/- 20.5%; radiochemical yield and > 90% radiochemical purity. Molar activity was 632 +/- 380 MBq/mu mol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by mu PET/CT imaging and more completely predicted the distribution kinetics than uptake of the [Ga-68]Ga-labeled ligands did. Although there are multiple challenges to the use of Ga-66 for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.