Juergen Karl Willmann MD, Presenter: Nothing to Disclose

Kai Chen, Abstract Co-Author: Nothing to Disclose

Mark Rollins MD, PhD, Abstract Co-Author: Nothing to Disclose

David Stephen Wang MD, Abstract Co-Author: Nothing to Disclose

Xiaoyuan Chen PhD, Abstract Co-Author: Nothing to Disclose

Sanjiv Sam Gambhir MD, PhD, Abstract Co-Author: Board of Directors, Lumera Corporation Stockholder, Lumera Corporation Stockholder, Pfizer Inc Consultant, Spectrum Dynamics Ltd Stockholder, Spectrum Dynamics Ltd Grant, Johnson & Johnson (ALZA Corporation) Committee member, Amgen Inc Scientific Advisory Board, Novartis AG (Chiron) Scientific Advisory Board, Siemens AG (PETNET Solutions) Royalties, Reed Elsevier Scientific Advisory Board, Genentech, Inc Scientific Advisory Board, General Electric Company Grant, General Electric Company (Amersham plc) Research collaboration, GlaxoSmithKline plc Scientific Advisory Board, GlaxoSmithKline plc Scientific Advisory Board, Intronn Inc Research collaboration, Intronn Inc Grant, Intronn Inc Scientific Advisory Board, Lumen Therapeutics Consultant, MediGene AG Scientific Advisory Board, MediGene AG Consultant, Millennium Pharmaceuticals, Inc Research collaboration, Pfizer Inc Grant, Pfizer Inc Consultant, Koninklijke Philips Electronics NV Scientific Advisory Board, Koninklijke Philips Electronics NV Consultant, Pathwork Diagnostics (Predicant Biosciences) Grant, Bayer AG Speaker, Siemens AG Scientific Advisory Board, Varian Medical Systems, Inc Scientific Advisory Board, VisualSonics Inc

Vascular endothelial growth factor-121 (VEGF121), an angiogenic protein secreted in response to hypoxic stress in therapeutic angiogenesis, binds to VEGF receptors (VEGFR) overexpressed on vessels of ischemic tissue. The purpose of this study was to evaluate PET imaging with 64Cu-VEGF121 for non-invasive spatial and quantitative monitoring of VEGFR expression in a murine model of hindlimb ischemia with and without treadmill exercise training.

64Cu-labeled VEGF121 and VEGFMutant were tested for VEGFR2 binding specificity in cell culture experiments. C57BL/6J mice (n = 46) were subjected to unilateral hindlimb ischemia by ligation of the femoral artery and reduced postoperative tissue perfusion compared to contralateral control hindlimb was evaluated with laser Doppler imaging. Longitudinal VEGFR2 expression in exercised and non-exercised mice was visualized with 64Cu-VEGF121 before, and at postoperative days 8, 15, 22, and 29 and correlated with postmortem gamma counting. Hindlimb muscle tissues were excised for immunohistochemistry and western blotting.

Compared with VEGFMutant, VEGF121 showed specific binding to VEGFR2. Perfusion in ischemic hindlimbs fell to 9% of non-ischemic hindlimb on postoperative day 1 and recovered to 82% on day 29. 64Cu-VEGF121 uptake in ischemic hindlimbs significantly (P < .001) increased from a control level of 0.61 %ID/g to 1.62 %ID/g at postoperative day 8, gradually decreased over the following 3 weeks (day 29, 0.59 %ID/g) and correlated with gamma counting (R2 = 0.99). Compared with non-exercised mice, 64Cu-VEGF121 uptake was significantly increased (P < .03) in exercised mice and correlated with VEGFR2 levels as obtained by western blotting (R2 = 0.76). Immunohistochemistry revealed increased VEGFR2 staining in ischemic hindlimb tissue.

PET imaging with 64Cu-VEGF121 allows a longitudinal spatial and quantitative monitoring of VEGFR2 expression in murine hindlimb ischemia and visualizes the effects of stimulated therapeutic angiogenesis after treadmill exercise training.

The current work in mice sets the groundwork for eventual translation of this PET approach for molecular imaging of therapeutic angiogenesis in patients.

Willmann, J, Chen, K, Rollins, M, Wang, D, Chen, X, Gambhir, S, Molecular Imaging of Therapeutic Angiogenesis in Murine Hindlimb Ischemia Using PET and ⁶⁴Cu-labeled Vascular Endothelial Growth Factor₁₂₁.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5014328.html