Journal article
PET of c-Met in Cancer with Cu-64-Labeled Hepatocyte Growth Factor
The Journal of nuclear medicine (1978), Vol.56(5), pp.758-763
05/01/2015
DOI: 10.2967/jnumed.115.154690
PMCID: PMC4417426
PMID: 25840981
Abstract
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)-1,4,7triazacyclononane-1,4,7-triacetic acid and labeled with Cu-64. 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 mu g of protein per 5 x 10(6) 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 Cu-64-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 Cu-64-NOTA-rh-HGF. Conclusion: This study provided initial evidence that Cu-64-NOTA-rh-HGF visualizes c-Met expression in vivo, an application that may prove useful for c-Met-targeted cancer therapy.
Details
- Title: Subtitle
- PET of c-Met in Cancer with Cu-64-Labeled Hepatocyte Growth Factor
- Creators
- Haiming Luo - University of Wisconsin–MadisonHao Hong - University of Wisconsin–MadisonMichael R. Slater - PromegaStephen A. Graves - University of Wisconsin–MadisonSixiang Shi - University of Wisconsin–MadisonYunan Yang - University of Wisconsin–MadisonRobert J. Nickles - University of Wisconsin–MadisonFrank Fan - PromegaWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- The Journal of nuclear medicine (1978), Vol.56(5), pp.758-763
- Publisher
- Soc Nuclear Medicine Inc
- DOI
- 10.2967/jnumed.115.154690
- PMID
- 25840981
- PMCID
- PMC4417426
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Number of pages
- 6
- Grant note
- University of Wisconsin-Madison NIBIB/NCI 1R01CA169365; P30CA014520; T32CA009206 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 125246-RSG-13-099-01-CCE / American Cancer Society W81XWH-11-10644; W81XWH-11-1-0648 / Department of Defense; United States Department of Defense
- Language
- English
- Date published
- 05/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383317702771
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