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HERO ID
4258464
Reference Type
Journal Article
Title
Evaluation of two novel ⁶⁴Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin αvβ₃
Author(s)
Hernandez, R; Czerwinski, A; Chakravarty, R; Graves, SA; Yang, Y; England, CG; Nickles, RJ; Valenzuela, F; Cai, W
Year
2015
Is Peer Reviewed?
Yes
Journal
European Journal of Nuclear Medicine and Molecular Imaging
ISSN:
1619-7070
EISSN:
1619-7089
Volume
42
Issue
12
Page Numbers
1859-1868
Language
English
PMID
26016906
DOI
10.1007/s00259-015-3085-7
Abstract
PURPOSE:
Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin αvβ3, 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 PEG4-SAA4-c(RGDfK), were constructed and conjugated to NOTA for (64)Cu labeling. Their integrin αvβ3-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the (64)Cu-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-PEG4-SAA4-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of (64)Cu-NOTA-(PEG)2-c(RGDfK) and (64)Cu-NOTA-PEG4-SAA4-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, (64)Cu-NOTA-PEG4-SAA4-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 αvβ3-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 αvβ3. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake.
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