Format

Send to

Choose Destination
J Nucl Med. 2015 May;56(5):758-63. doi: 10.2967/jnumed.115.154690. Epub 2015 Apr 3.

PET of c-Met in Cancer with ⁶⁴Cu-Labeled Hepatocyte Growth Factor.

Author information

1
Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
2
Promega Corp., Madison, Wisconsin.
3
Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
4
Materials Science Program, University of Wisconsin-Madison, Madison, Wisconsin; and.
5
Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin Materials Science Program, University of Wisconsin-Madison, Madison, Wisconsin; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin wcai@uwhealth.org.

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)-1,4,7-triazacyclononane-1,4,7-triacetic acid and labeled with (64)Cu. 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 × 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 (64)Cu labeling, PET imaging revealed specific and prominent uptake of (64)Cu-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 (64)Cu-NOTA-rh-HGF.

CONCLUSION:

This study provided initial evidence that (64)Cu-NOTA-rh-HGF visualizes c-Met expression in vivo, an application that may prove useful for c-Met-targeted cancer therapy.

KEYWORDS:

64Cu; c-Met; cancer; hepatocyte growth factor (HGF); positron emission tomography (PET)

PMID:
25840981
PMCID:
PMC4417426
DOI:
10.2967/jnumed.115.154690
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center