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J Nucl Med. 2008; 49 (Supplement 1):184P
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Cardiovascular: Basic Science

Basic Science Posters

Evaluation of a RGD-dendrimer labeled with 76Br in hindlimb ischemia mouse model

Aviv Hagooly1, Adah Almutairi2, Raffaella Rossin1, Monica Shokeen1, Ashwin Ananth2, Carolyn Anderson1, Dana Abendschein3, Jean Fréchet2 and Michael Welch1

1 Department of Radiology, Washington University School of Medicine, St. Louis, Missouri; ; 2 College of Chemistry, University of California, Berkeley, California; ; 3 Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri

804

Objectives: The goal of this work was to evaluate a biodegradable RGD-targeted dendrimer in an animal model expressing the {alpha}Vβ3 integrin as a candidate for targeted therapeutic and diagnostic agents for vascular disease.

Methods: Hindlimb hischemia (HLI) was achieved by performing a double ligation of the femoral artery in C57BL/6 mice followed by excision of the artery segment (right thigh). A sham injury was performed in the left thigh. Seven days post injury, the RGD-dendrimer and the non-targeted dendrimer were labeled with 76Br and injected into the mice. The accumulation of the labeled polymers in the mouse thighs was evaluated by small animal PET and biodistribution (n=6-8).

Results: PET imaging showed higher accumulation of the RGD-dendrimer in the HLI site compared to the sham injury site and no specific binding of the non targeted compound was observed. SUV and post-PET biodistribution analysis demonstrated a high right-to-left ratio in the thigh muscle, especially at the distal area (3.1 ± 1.3), reasonably due to an ongoing revascularization process in the ischemic muscle.

Conclusions: An animal model of vascular remodeling was established and used to evaluate {alpha}Vβ3-targeted dendrimers in vivo. The results suggest specific interaction between the RGD-dendrimer and the target tissue. This approach holds promise for molecular imaging of vascular injury.

Research Support: This material is based upon work supported by the NIH as a Program of Excellence in Nanotechnology (HL080729). The production of 76Br is supported by a grant from the NCI (CA86307).





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Right arrow Articles by Welch, M.