Division of Radiopharmaceutical Sciences and MI3, Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA.
Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10065, USA.
Molecules. 2018 Oct 9;23(10):2575. doi: 10.3390/molecules23102575.
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.
新兴的延长小分子放射性配体血浆半衰期的兴趣需要考虑在更长时间点（> 8 小时）进行 PET 成像的适当放射性核素。在候选正电子发射放射性核素中，Ga（t = 9.5 h，β+ = 57%）具有适合的核和化学性质，可用于标记和 PET 成像这种类型的放射性配体。我们研究了 Ga 在临床前筛选和评估结合白蛋白的 PSMA 靶向小分子中的价值。Ga 通过辐照 Zn 靶来产生。Ga 离子通过优化的 UTEVA 阴离子交换柱与 Zn 离子分离，该柱保留了 99.99987%的 Zn 离子，允许 Ga 以 90.2 ± 2.8%的回收率回收。三种配体以 46.4 ± 20.5%的产率标记；放射化学产率和>90%的放射化学纯度。摩尔活性为 632 ± 380 MBq/µmol。通过 µPET/CT 成像测定了 1、3、6 和 24 小时时肿瘤和肾脏的摄取，其比 [Ga]Ga 标记配体的摄取更完全地预测了分布动力学。尽管 Ga 用于临床 PET 成像存在多种挑战，但它可以成为配体筛选和 24 小时后临床前成像的有价值的研究工具。
