RT Journal Article SR Electronic T1 Radiolabeled RGD Uptake and αv Integrin Expression Is Enhanced in Ischemic Murine Hindlimbs JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 472 OP 478 VO 46 IS 3 A1 Kyung-Han Lee A1 Kyoung-Ho Jung A1 Sung-Hee Song A1 Dong Hyun Kim A1 Byung Chul Lee A1 Hyun Ju Sung A1 Yu-Mi Han A1 Yearn Seong Choe A1 Dae Yoon Chi A1 Byung-Tae Kim YR 2005 UL http://jnm.snmjournals.org/content/46/3/472.abstract AB Radiolabeled RGD peptides that target αvβ3 integrin are promising tracers for imaging tumor angiogenesis. Integrins and angiogenesis also play important roles in healing of ischemic lesions. Thus, we investigated the biodistribution of radiolabeled RGD and expression of αv integrin in a mouse model of hindlimb ischemia. Methods: 125I-3-Iodo-d-Tyr4-cyclo(-Arg-Gly-Asp-d-Tyr-Val-) (125I-c(RGD(I)yV)) was synthesized and tested for endothelial binding. Hindlimb ischemia was induced in ICR mice through femoral artery ablation, and perfusion was measured with laser Doppler blood flowmetry. 125I-c(RGD(I)yV) biodistribution was evaluated in control animals (n = 7) and ischemic models on day 3, 8, or 14 (n = 6 each). Control experiments were performed using a radiolabeled peptide with a scrambled amino acid sequence (125I-GfVGV). Microsections of hindlimb tissue were immunostained for αv integrin expression and stained with alkaline phosphatase to localize vascular endothelial cells. Results: 125I-c(RGD(I)yV) retained specific binding to human umbilical vein endothelial cells. Perfusion in ischemic hindlimbs immediately fell to 10% ± 4% of contralateral levels and gradually recovered to 22% ± 11% and 64% ± 9% on days 8 and 14, respectively. 125I-c(RGD(I)yV) uptake in ischemic muscles significantly increased from a control level of 0.16 ± 0.05 %ID/g (percentage injected dose per gram of tissue) to 0.85 ± 0.76 %ID/g at day 3, 0.43 ± 0.23 %ID/g at day 8, and 0.43 ± 0.28 %ID/g at day 14 (all P < 0.05). Ischemic muscle-to-lung count ratios had a virtually identical trend: 0.42 ± 0.25 for controls, 2.34 ± 1.70 at day 3 (P < 0.02), 1.46 ± 0.52 at day 8 (P < 0.001), and 1.39 ± 0.94 at day 14 (P < 0.02). In contrast, uptake of the control peptide in ischemic hindlimbs was not different from that of controls. Immunohistochemistry revealed substantially increased αv integrin staining in ischemic hindlimb tissue. Conclusion: Radioiodine RGD uptake is significantly enhanced in ischemic hindlimbs of a mouse model, and is accompanied by an increase in αv integrin expression. Further investigation is thus warranted to illuminate the potential role of radiolabeled RGD for noninvasive monitoring of peripheral ischemic lesions.