A Novel Conjugable Translocator Protein Ligand Labeled with a Fluorescence Dye for in Vitro Imaging

• Published in: Bioconjugate chemistry Vol. 18; no. 4; pp. 1118 - 1122
• Main Authors: Bai, Mingfeng, Wyatt, Shelby K, Han, Zeqiu, Papadopoulos, Vassilios, Bornhop, Darryl J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-07-2007
• Subjects: Amino acids; Animals; Benzodiazepinones - chemistry; Benzodiazepinones - metabolism; Biochemistry; Cell Line, Tumor; Dyes; Fluorescent Dyes - chemistry; Fluorescent Dyes - metabolism; Humans; Ligands; Medical imaging; Microscopy, Fluorescence; Molecules; Protein Binding; Proteins; Rats; Receptors, GABA - chemistry; Receptors, GABA - metabolism; Rhodamines - chemistry; Rhodamines - metabolism
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc060381r

A conjugable analogue of the benzodiazepine 4‘ ‘-chlorodiazepam (Ro5-4864), C6Ro5-4864 was synthesized to probe the binding sites of translocator protein (18 kDa; TSPO), previously known as the peripheral benzodiazepine receptor for molecular imaging. The amino group in this analogue allows universal conjugation to signaling molecules. Lissamine−C6Ro5-4864, synthesized from C6Ro5-4864 and a lissamine fluorescence dye, was investigated in this study. This imaging agent exhibited micromolar binding affinity (K i = 2.6 μM) to TSPO and was successfully imaged in TSPO rich glioma and breast cancer cell lines. These findings suggest that C6Ro5-4864 may provide opportunities in imaging disease states where TSPO levels are affected, such as cancer and neurologic diseases.