一种用于感染和炎症成像的肼基烟酰胺共轭白三烯B4受体拮抗剂的99mTc标记

99mTc-Labeling of a hydrazinonicotinamide-conjugated LTB(4) receptor antagonist useful for imaging infection and inflammation.

作者信息

Liu Shuang, Harris Anthony R, Williams Neal E, Edwards D Scott

机构信息

Bristol-Myers Squibb Medical Imaging, 331 Treble Cove Road, North Billerica, Massachusetts 01862, USA.

出版信息

Bioconjug Chem. 2002 Jul-Aug;13(4):881-6. doi: 10.1021/bc010120b.

DOI:10.1021/bc010120b

PMID:12121145

Abstract

This report describes the (99m)Tc labeling of a hydrazinonicotinamide (HYNIC)-conjugated LTB(4) receptor antagonist (SG380). The ternary ligand technetium complex [(99m)Tc(SG38)(tricine)(TPPTS)] (RP517) was prepared using a non-SnCl(2)-containing formulation ((2001) J. Pharm. Sci. 90, 114-123). Unlike other HYNIC-conjugated small biomolecules, SG380 is lipophilic and has low solubility in the kit matrix. Using a combination of a solubilizing agent (Lysolecithin) and a cosolvent (ethanol), we have developed a new formulation for routine preparation of RP517. Using this formulation, RP517 can be prepared in high radiochemical purity (RCP > 90%) and remains stable in the kit matrix for at least 6 h. We also prepared the corresponding (99)Tc analogue, [(99)Tc]RP517. An HPLC concordance experiment using RP517 and [(99)Tc]RP517 showed that the same technetium complex was prepared at both the tracer and macroscopic levels. The LC-MS data are completely consistent with the 1:1:1:1 composition for Tc:SG380:tricine:TPPTS.

摘要

本报告描述了肼基烟酰胺（HYNIC）偶联的白三烯B4（LTB4）受体拮抗剂（SG380）的（99m）Tc标记。使用不含SnCl2的配方（（2001年）《药物科学杂志》90卷，114 - 123页）制备了三元配体锝配合物[（99m）Tc（SG38）（三乙醇胺）（三（间磺酸钠苯基）膦）]（RP517）。与其他HYNIC偶联的小生物分子不同，SG380具有亲脂性，在试剂盒基质中的溶解度较低。通过使用增溶剂（溶血卵磷脂）和助溶剂（乙醇）的组合，我们开发了一种用于常规制备RP517的新配方。使用该配方，可以制备出高放射化学纯度（RCP > 90%）的RP517，并且在试剂盒基质中至少稳定6小时。我们还制备了相应的（99）Tc类似物[（99）Tc]RP517。使用RP517和[（99）Tc]RP517进行的HPLC一致性实验表明，在示踪剂和宏观水平上制备的是相同的锝配合物。LC-MS数据与Tc:SG380:三乙醇胺:三（间磺酸钠苯基）膦的1:1:1:1组成完全一致。