TY - JOUR T1 - PET of c-Met in Cancer with <sup>64</sup>Cu-Labeled Hepatocyte Growth Factor JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 758 LP - 763 DO - 10.2967/jnumed.115.154690 VL - 56 IS - 5 AU - Haiming Luo AU - Hao Hong AU - Michael R. Slater AU - Stephen A. Graves AU - Sixiang Shi AU - Yunan Yang AU - Robert J. Nickles AU - Frank Fan AU - Weibo Cai Y1 - 2015/05/01 UR - http://jnm.snmjournals.org/content/56/5/758.abstract N2 - The hepatocyte growth factor (HGF) and its receptor, c-Met, are actively involved in tumor progression and metastasis and are closely associated with a poor prognostic outcome for cancer patients. Thus, the development of PET agents that can assess c-Met expression would be extremely useful for diagnosing cancer and subsequently monitoring response to c-Met–targeted therapies. Here, we report the characterization of recombinant human HGF (rh-HGF) as a PET tracer for detection of c-Met expression in vivo. Methods: rh-HGF was expressed in human embryonic kidney 293 cells and purified by nickel-nitrilotriacetic acid affinity chromatography. The concentrated rh-HGF was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid and labeled with 64Cu. c-Met binding evaluation by flow cytometry was performed on both U87MG and MDA-MB-231 cell lines, which have a high level and a low level, respectively, of c-Met. PET imaging and biodistribution studies were performed on nude mice bearing U87MG and MDA-MB-231 xenografted tumors. Results: The rh-HGF expression yield was 150–200 μg of protein per 5 × 106 cells after a 48-h transfection, with purity of approximately 85%–90%. Flow cytometry examination confirmed that rh-HGF had a strong and specific capacity to bind to c-Met. After 64Cu labeling, PET imaging revealed specific and prominent uptake of 64Cu-NOTA-rh-HGF in c-Met–positive U87MG tumors (percentage injected dose per gram, 6.8 ± 1.8 at 9 h after injection) and significantly lower uptake in c-Met–negative MDA-MB-231 tumors (percentage injected dose per gram, 1.8 ± 0.6 at 9 h after injection). The fact that sonication-denatured rh-HGF had significantly lower uptake in U87MG tumors, along with histology analysis, confirmed the c-Met specificity of 64Cu-NOTA-rh-HGF. Conclusion: This study provided initial evidence that 64Cu-NOTA-rh-HGF visualizes c-Met expression in vivo, an application that may prove useful for c-Met–targeted cancer therapy. ER -