66 Ga: 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, ⁶⁶ Ga (t _1/2 = 9.5 h, β+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of ⁶⁶ Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. ⁶⁶ Ga was produced by irradiation of a ^nat Zn target. ⁶⁶ Ga ³⁺ ions were separated from Zn ²⁺ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn ²⁺ ions and allowed 90.2 ± 2.8% recovery of ⁶⁶ Ga ³⁺ . Three ligands were radiolabeled in 46.4 ± 20.5%; radiochemical yield and >90% radiochemical purity. Molar activity was 632 ± 380 MBq/µmol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by µPET/CT imaging and more completely predicted the distribution kinetics than uptake of the [ ⁶⁸ Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of ⁶⁶ Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.