We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with ⁶⁴Cu for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5·NHAc dendrimers were then radiolabeled with ⁶⁴Cu via the DOTA chelation. We show that the FA modification renders the dendrimers with targeting specificity to cancer cells overexpressing FR in vitro. Importantly, the radiolabeled ⁶⁴Cu-DOTA-FA-FI-G5·NHAc dendrimers can be used as a nanoprobe for specific targeting of FR-overexpressing cancer cells in vitro and targeted microPET imaging of the FR-expressing xenografted tumor model in vivo. The developed ⁶⁴Cu-labeled multifunctional dendrimeric nanoprobe may hold great promise to be used for targeted PET imaging of different types of FR-expressing cancer.

中文翻译：

---

用于目标肿瘤PET成像的64Cu标签多功能树状聚合物。

我们报告使用多功能叶酸（FA）修饰的树状聚合物作为平台以放射性标记与⁶⁴ Cu的叶酸受体（FR）表达肿瘤的PET成像。在这项研究中，用异硫氰酸荧光素（FI），FA和1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸顺序修饰胺端基的第5代（G5）聚（酰胺基胺）树状聚合物（DOTA），然后将剩余的树枝状大分子末端胺乙酰化。然后将形成的多功能DOTA-FA-FI-G5·NHAc树状聚合物通过DOTA螯合用⁶⁴ Cu进行放射性标记。我们表明，FA修饰使得树状聚合物具有靶向特异性的癌细胞在体外超表达FR 。重要的是，放射性标记的⁶⁴Cu-DOTA-FA-FI-G5·NHAc树状大分子可用作纳米探针，可在体外特异性靶向表达FR过高的癌细胞，并在体内对表达FR的异种移植肿瘤模型进行靶向microPET成像。已开发的⁶⁴ Cu标记的多功能树枝状大分子纳米探针可能具有广阔的前景，可用于不同类型表达FR的癌症的靶向PET成像。