Development of a novel 99m Tc-labeled small molecular antagonist for CXCR4 positive tumor imaging.
The chemokine receptor 4 (CXCR4) has been an attractive molecular target for tumor imaging, because it is overexpressed in many tumor types and involved in tumor progression and metastasis. The purpose of this study is to examine the CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 hours. In vitro cell binding experiments were performed with Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably transfected to express CXCR4) cell lines. Small animal single photon emission computed tomography/computed tomography imaging studies in nude mice bearing MCF-7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05), and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465 (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential single photon emission computed tomography radiotracer for CXCR4 imaging.
['Zhang|Xuran|X|', 'You|Linyi|L|', 'Chen|Shuting|S|', 'Gao|Mengna|M|', 'Guo|Zhide|Z|', 'Du|Jin|J|', 'Lu|Jie|J|0000-0001-6351-0508', 'Zhang|Xianzhong|X|']
D000818:Animals D016466:CHO Cells D006224:Cricetinae D003412:Cricetulus D005260:Female D006801:Humans D061986:MCF-7 Cells D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009374:Neoplasms, Experimental D011725:Pyridines D019275:Radiopharmaceuticals D019718:Receptors, CXCR4 D000072098:Single Photon Emission Computed Tomography Computed Tomography D013667:Technetium
CXCR4 tumor imaging AMD3465 SPECT Technetium-99m