Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
Nanoscale. 2019 Nov 28;11(46):22248-22254. doi: 10.1039/c9nr08508d.
Most current nanoparticle-based PET tracers are radiolabeled through metal chelators conjugated on the nanoparticle surface. Metal chelation usually requires sophisticated optimization and may impact the physical or chemical properties of nanoparticles, which leads to the changes in their distribution and pharmacokinetics in vivo. A chelator-free radiolabeling approach is thus highly desirable. Here, we report that zinc sulfide (ZnS) quantum dots (QDs) can be rapidly radiolabeled with 68Ga or 64Cu through cation exchange without chelators. The radiolabeling was accomplished in times as short as 5 min at 37 °C in aqueous solution, yielding a high labeling efficiency and radiochemical purity for both isotopes. Surface functionalization with targeting peptides was also readily achieved to enable or enhance the cellular uptake of QDs. In vivo PET imaging showed that 64Cu-labeled QDs had a much higher tumor uptake (7.3% ID g-1) than 64Cu-DOTA in a murine cancer model. Overall, this study presents a QD-based platform to achieve convenient and chelator-free radiolabeling, and improve PET imaging of solid tumors.
大多数当前基于纳米粒子的 PET 示踪剂是通过连接在纳米粒子表面的金属螯合剂进行放射性标记的。金属螯合通常需要复杂的优化，并且可能会影响纳米粒子的物理或化学性质，从而导致其在体内的分布和药代动力学发生变化。因此，非常需要一种无螯合剂的放射性标记方法。在这里，我们报告说，硫化锌 (ZnS) 量子点 (QD) 可以通过阳离子交换在没有螯合剂的情况下快速与 68Ga 或 64Cu 进行放射性标记。放射性标记可以在 37°C 的水溶液中在短短 5 分钟内完成，对于两种同位素都具有高的标记效率和放射化学纯度。通过靶向肽的表面功能化也可以轻松实现，从而能够或增强 QD 的细胞摄取。体内 PET 成像显示，在小鼠癌症模型中，64Cu 标记的 QD 的肿瘤摄取（7.3% ID g-1）明显高于 64Cu-DOTA。总的来说，这项研究提出了一种基于 QD 的平台，以实现方便且无螯合剂的放射性标记，并改善实体瘤的 PET 成像。
