Journal article
Evaluation of two novel Cu-64-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin alpha(v)beta(3)
European journal of nuclear medicine and molecular imaging, Vol.42(12), pp.1859-1868
11/01/2015
DOI: 10.1007/s00259-015-3085-7
PMCID: PMC4591102
PMID: 26016906
Abstract
Purpose Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin alpha(v)beta(3), may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues.
Methods Two cyclic RGDfK derivatives, (PEG)(2)-c(RGDfK) and PEG(4)-SAA(4)-c(RGDfK), were constructed and conjugated to NOTA for Cu-64 labeling. Their integrin alpha(v)beta(3)-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the Cu-64-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers.
Results The IC50 values of NOTA-(PEG)(2)-c(RGDfK) and NOTA-PEG(4)-SAA(4)-c(RGDfK) were 444 +/- 41 nM and 288 +/- 66 nM, respectively. Dynamic PET data of Cu-64-NOTA-(PEG)(2)-c(RGDfK) and Cu-64-NOTA-PEG(4)-SAA(4)-c(RGDfK) showed similar circulation t (1/2) and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, Cu-64-NOTA-PEG(4)-SAA(4)-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin alpha(v)beta(3)-specificity of the peptides.
Conclusion Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin alpha(v)beta(3). These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake.
Details
- Title: Subtitle
- Evaluation of two novel Cu-64-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin alpha(v)beta(3)
- Creators
- Reinier Hernandez - University of Wisconsin–MadisonAndrzej Czerwinski - Peptides InternationalRubel Chakravarty - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonYunan Yang - University of Wisconsin–MadisonChristopher G. England - University of Wisconsin–MadisonRobert J. Nickles - University of Wisconsin–MadisonFrancisco Valenzuela - Peptides InternationalWeibo Cai - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- European journal of nuclear medicine and molecular imaging, Vol.42(12), pp.1859-1868
- Publisher
- Springer Nature
- DOI
- 10.1007/s00259-015-3085-7
- PMID
- 26016906
- PMCID
- PMC4591102
- ISSN
- 1619-7070
- eISSN
- 1619-7089
- Number of pages
- 10
- Grant note
- T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 1831/FNPDR/2013 / US Department of States Fulbright Scholar Program DGE-1256259 / National Science Foundation; National Science Foundation (NSF) NIBIB/NCI 1R01CA169365; P30CA014520; T32CA009206; 5T32GM08349 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Wisconsin-Madison W81XWH-11-1-0644; W81XWH-11-1-0648 / Department of Defense; United States Department of Defense 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
- Language
- English
- Date published
- 11/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383899802771
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