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, Ga (t = 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 Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. Ga was produced by irradiation of a Zn target. Ga ions were separated from Zn ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn ions and allowed 90.2 ± 2.8% recovery of Ga. 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 [Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.