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      Evaluation of Two Novel 64Cu-labelled RGD Peptide Radiotracers for Enhanced PET Imaging of Tumor Integrin α vβ 3

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          Abstract

          Purpose

          Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin α vβ 3, may offer advantages in image contrast, time for imaging, and low uptake in non-target tissues.

          Methods

          Two cyclic RGDfK derivatives, (PEG) 2-c(RGDfK) and PEG 4-SAA 4-c(RGDfK), were constructed and conjugated to NOTA for 64Cu labeling. Their integrin α vβ 3-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the 64Cu-labelled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h post-injection (p.i.). Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers.

          Results

          The IC 50 values of NOTA-(PEG) 2-c(RGDfK) and NOTA-PEG 4-SAA 4-c(RGDfK) were 444 ± 41, and 288 ± 66 nM, respectively. Dynamic PET data of 64Cu-NOTA-(PEG) 2-c(RGDfK) and 64Cu-NOTA-PEG 4-SAA 4-c(RGDfK) unveiled similar circulation t 1/2 and peak tumor uptake of ~4 %ID/g for both tracers. Due to its marked hydrophilicity, 64Cu-NOTA-PEG 4-SAA 4-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintaining 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 α vβ 3-specificity of the peptides.

          Conclusion

          Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed a fast, high-contrast PET imaging of tumor associated integrin α vβ 3. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptakes.

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          Author and article information

          Journal
          101140988
          27055
          Eur J Nucl Med Mol Imaging
          Eur. J. Nucl. Med. Mol. Imaging
          European journal of nuclear medicine and molecular imaging
          1619-7070
          1619-7089
          15 May 2015
          28 May 2015
          November 2015
          01 November 2016
          : 42
          : 12
          : 1859-1868
          Affiliations
          [1 ]Department of Medical Physics, University of Wisconsin - Madison, WI, USA, 53705
          [2 ]Peptides International, Inc., Louisville, K Y, USA, 40299
          [3 ]Department of Radiology, University of Wisconsin - Madison, WI, USA, 53705
          [4 ]University of Wisconsin Carbone Cancer Center, Madison, WI, USA, 53705
          Author notes
          Corresponding author: Weibo Cai, PhD, wcai@ 123456uwhealth.org ; phone: 608-262-1749;f ax: 608-265-0614
          Article
          PMC4591102 PMC4591102 4591102 nihpa690674
          10.1007/s00259-015-3085-7
          4591102
          26016906
          bdfcb327-0201-45fe-987d-36a1ccf74711
          History
          Categories
          Article

          positron emission tomography (PET),molecular imaging,Integrin αvβ3 ,Copper-64 (64Cu),RGD peptide,angiogenesis

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