Synthesis & biological evaluation of ^99mTc-AMD3465 as a SPECT tracer for CXCR4 receptor imaging.

Objectives: Purpose A number of attempts have been made to non-invasively image CXCR4 receptor, such as ⁶⁴Cu-AMD3100 & ⁶⁸Ga-Pentixafor. AMD3465 was successfully labeled with ⁶⁴Cu & evaluated for imaging CXCR4 expression in a tumor. We tried to use the monocyclam to form strong complexes with ^99mTc to develop ^99mTc-AMD3465 as an imaging agent for SPECT. Methods AMD 3465 was synthesized by a four-step reaction from the cyclam. ^99mTc-AMD3465 was labeled with ^99mTcO₄^- by reduction with stannous chloride. The homologous binding assay was performed in Jurkat-T cells. Biodistribution & SPECT images were obtained in mice bearing H460 tumor. Results The radiochemical purities (RCP) of ^99mTc-AMD3465 were over 99 %. Heterologous binding assays showed IC50 values of 72.2±1.4μM for ^99mTc-AMD3465. The partition co-efficient (log P) value of ^99mTc-AMD3465 was -2.67, suggesting this radiotracer was hydrophilic. The value was the same as that of ⁶⁴Cu-AMD3465, which was -2.67. The accumulation of ^99mTc-AMD3465 was higher in the liver, spleen & bone, which is consistent with the known high expression of CXCR4 in these organs. The H460 tumor was seen clearly after injection of ^99mTc-AMD3465 . The T/NT was 2.6±1.2 at 60 min. Conclusion ^99mTc-AMD3465 showed specific binding to organs with high CXCR4 expression, & could be used to image CXCR4 receptors.