The synthesis and investigation of 5-[125I]iodoindol-3-yl-beta-d-galactopyranoside ([125I]IBDG) as a radioligand for single-photon emission computed tomography (SPECT) imaging of b-galactosidase expression are described. No-carrier-added [125I]IBDG was synthesized by a radioiododestannylation approach in > 75% overall radiochemical yield and > 99% radiochemical purity. [125I]IBDG was evaluated as a substrate using beta-galactosidase-expressing (D54L) and nonexpressing (D54) human glioma cell lines. A 24-hour incubation of this substrate with cultured cells revealed a 6.5-fold greater intracellular trapping of radioactivity in D54L cells compared with D54 cells. Systemic delivery of [125I]IBDG in nude mice bearing D54L tumors failed to show significant trapping of radioactivity within these tumors by SPECT imaging. In contrast, intratumoral injection of the substrate resulted in efficient trapping of radioactivity in D54L tumors but not D54 tumors, resulting in clear SPECT visualization of the former tumor. Based on dynamic SPECT imaging and blood metabolite analysis, we conclude that although [125I]IBDG is an efficient in vivo substrate for beta-galactosidase, its rapid renal clearance hampers its intratumoral availability on systemic administration.

中文翻译：

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5-[125I]碘吲哚-3-基-β-D-吡喃半乳糖苷作为β-半乳糖苷酶成像放射性配体的放射合成和评估。

描述了 5-[125I]碘吲哚-3-基-β-d-吡喃半乳糖苷 ([125I]IBDG) 作为放射性配体用于 b-半乳糖苷酶表达的单光子发射计算机断层扫描 (SPECT) 成像的合成和研究。未添加载体的[125I]IBDG是通过放射性碘脱甲烷基化方法合成的，总放射化学产率> 75%，放射化学纯度> 99%。使用表达β-半乳糖苷酶(D54L)和不表达(D54)的人神经胶质瘤细胞系评估[125I]IBDG作为底物。将此底物与培养细胞一起孵育 24 小时，结果显示 D54L 细胞的细胞内放射性捕获量是 D54 细胞的 6.5 倍。通过 SPECT 成像，在携带 D54L 肿瘤的裸鼠中全身递送 [125I]IBDG 未能显示出这些肿瘤内放射性的显着捕获。相比之下，肿瘤内注射底物可有效捕获 D54L 肿瘤而非 D54 肿瘤中的放射性，从而使前一个肿瘤获得清晰的 SPECT 可视化。基于动态 SPECT 成像和血液代谢物分析，我们得出结论，尽管 [125I]IBDG 是 β-半乳糖苷酶的有效体内底物，但其快速的肾脏清除阻碍了其全身给药的瘤内可用性。