Radiolabeled RGD Uptake and αv Integrin Expression Is Enhanced in Ischemic Murine Hindlimbs

Journal of Nuclear Medicine

Byung-Tae Kim¹  Hyun Ju Sung¹  Dae Yoon Chi¹  Kyung-Han Lee¹  Byung Chul Lee¹  Dong Hyun Kim¹  Yu-Mi Han¹  Kyoung-Ho Jung¹  Sung-Hee Song¹  Yearn Seong Choe¹ 

关键词: RGD peptides;    integrin;    ischemia;    angiogenesis;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown