带有 NOTA 螯合剂的 4-N-烷酰基和 4-N-烷基吉西他滨类似物用于 68 镓标记。
4-N-Alkanoyl and 4-N-alkyl gemcitabine analogues with NOTA chelators for 68-gallium labelling.
机构信息
Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, United States.
Department of Biomedical Engineering, Florida International University, Miami, FL 33199, United States.
出版信息
Bioorg Med Chem. 2018 Nov 15;26(21):5624-5630. doi: 10.1016/j.bmc.2018.10.007. Epub 2018 Oct 12.
The conjugation of 4-N-(3-aminopropanyl)-2'-deoxy-2',2'-difluorocytidine with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) ligand in 0.1 M NaCO buffer (pH 11) at ambient temperature provided 4-N-alkylgemcitabine-NOTA chelator. Incubation of latter with excess of gallium(III) chloride (GaCl) (0.6 N AcONa/HO, pH = 9.3) over 15 min gave gallium 4-N-alkylgemcitabine-NOTA complex which was characterized by HRMS. Analogous [Ga]-complexation of 4-N-alkylgemcitabine-NOTA conjugate proceeded with high labeling efficiency (94%-96%) with the radioligand almost exclusively found in the aqueous layer (∼95%). The high polarity of the gallium 4-N-alkylgemctiabine-NOTA complex resulted in rapid renal clearance of the Ga-labelled radioligand in BALB/c mice.
将 4-N-(3-氨基丙基)-2'-去氧-2',2'-二氟胞苷与 2-(对异硫氰酸苯甲基)-1,4,7-三氮杂环壬烷-1,4,7-三乙酸（SCN-Bn-NOTA）配体在 0.1 M NaCO 缓冲液（pH 11）中于环境温度下进行缀合，得到 4-N-烷基吉西他滨-NOTA 螯合剂。将后者与过量的三氯化镓（GaCl）（0.6 N AcONa/HO，pH = 9.3）在 15 分钟以上孵育，得到 4-N-烷基吉西他滨-NOTA 镓配合物，并用高分辨质谱（HRMS）进行了表征。4-N-烷基吉西他滨-NOTA 缀合物的类似 [Ga]-配合作用具有很高的标记效率（94%-96%），放射性配体几乎完全存在于水相（约 95%）中。由于镓 4-N-烷基吉西他滨-NOTA 配合物的高极性，导致 Ga 标记的放射性配体在 BALB/c 小鼠中迅速经肾脏清除。
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