Journal article
PET Imaging of VEGFR-2 Expression in Lung Cancer with Cu-64-Labeled Ramucirumab
The Journal of nuclear medicine (1978), Vol.57(2), pp.285-290
02/01/2016
DOI: 10.2967/jnumed.115.166462
PMCID: PMC4738068
PMID: 26541778
Abstract
Lung cancer accounts for 17% of cancer-related deaths worldwide, and most patients pretent with locally advanced or metastatic disease. Novel PET imaging agents for assessing vascular endothelial growth factor receptor-2 (VEGFR-2) expression can be used for detecting VEGFR-2-positive malignancies and subsequent monitoring of therapeutic response to VEGFR-2-targeted therapies. Here, we report the synthesis and characterization of an antibody based imaging agent for PET imaging of VEGFR-2 expression in vivo. Methods: Ramucirumab (named RamAb), a fully humanized IgG1 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyI)1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with Cu-64. Flow cytometry analysis and microscopy studies were performed to compare the VEGFR-2 binding affinity of RamAb and NOTA-RamAb. PET imaging and biodistribution studies were performed in nude mice bearing HCC4006 and A549 xenograft tumors. Ex vivo histopathology was performed to elucidate the expression patterns of VEGFR-2 in different tissues and organs to validate in vivo results. Results: Flow cytometry examination revealed the specific binding capacity of fluorescein isothiocyanate-RamAb to VEGFR-2, and no difference in VEGFR-2 binding affinity was seen between RamAb and NOTA-RamAb. After being labeled with Cu-64, PET imaging revealed specific and prominent uptake of Cu-64-NOTA-RamAb in VEGFR-2-positive HCC4006 tumors (9.4 +/- 0.5 percentage injected dose per gram at 48 h after injection; n = 4) and significantly lower uptake in VEGFR-2-negative A549 tumors (4.3 +/- 0.2 percentage injected dose per gram at 48 h after injection; n = 3). Blocking experiments revealed significantly lower uptake in HCC4006 tumors, along with histology analysis, further-confirming the VEGFR-2 specificity of Cu-64-NOTA-RamAb. Conclusion: This study provides initial evidence that Cu-64-NOTA-RamAb can function as a PET imaging agent for visualizing VEGFR-2 expression in vivo, which may also find potential applications in monitoring the treatment response of VEGFR-2-targeted cancer therapy.
Details
- Title: Subtitle
- PET Imaging of VEGFR-2 Expression in Lung Cancer with Cu-64-Labeled Ramucirumab
- Creators
- Haiming Luo - University of Wisconsin–MadisonChristopher G. England - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonHaiyan Sun - University of Wisconsin–MadisonGlenn Liu - University of Wisconsin Carbone Cancer CenterRobert I. Nickles - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- The Journal of nuclear medicine (1978), Vol.57(2), pp.285-290
- Publisher
- Soc Nuclear Medicine Inc
- DOI
- 10.2967/jnumed.115.166462
- PMID
- 26541778
- PMCID
- PMC4738068
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Number of pages
- 6
- Grant note
- P30CA014520; R01CA169365; T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) University of Wisconsin-Madison W81XWH-11-1-0644 / Department of Defense; United States Department of Defense NIBIB/NCI 1R01CA169365; P30CA014520; T32CA009206 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 125246-RSG-13-099-01-CCE / American Cancer Society
- Language
- English
- Date published
- 02/01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383279502771
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