{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:40:15Z","timestamp":1753890015836,"version":"3.41.2"},"reference-count":27,"publisher":"IMR Press","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Background: Peripheral arterial disease (PAD) can severely compromise limb vitality and function. Angiogenesis plays an important role in healing of ischemic lesions. Radiolabeled RGD (Arg-Gly-Asp) peptides specifically targeting \u03b1v\u03b23 integrin are promising tracers for imaging angiogenesis. In this study, we investigated the application of a one-step labeled RGD in evaluation of angiogenesis and therapy response in a mouse model of hindlimb ischemia (HI) by positron emission tomography (PET). Methods: HI was induced by ablation of the femoral artery in mice. PET imaging using 18F-AlF-NOTA-PRGD2 (18F-PRGD2) tracer was performed at day 0 (pre-surgery) and days 3, 7, 14, and 21 after surgery to evaluate hindlimb angiogenesis longitudinally and noninvasively. The control peptide RAD (Arg-Ala-Asp) labeled with a similar procedure and a block agent were used to confirm the specific binding of 18F-PRGD2 to \u03b1v\u03b23 integrin. Ex vivo CD31 staining was performed to detect angiogenesis. In addition, the angiogenic therapy response was monitored with 18F-PRGD2 tracer and immunofluorescence staining to confirm the imaging data. Results: The successful establishment of HI model was confirmed by ultrasound imaging and laser doppler perfusion imaging (LDPI). Specific binding of 18F-PRGD2 to \u03b1v\u03b23 integrin was validated by minimal tracer uptake of the control peptide RAD and significant decrease of tracer accumulation when a block agent was added. Local accumulation of 18F-RRGD2 in ischemic hindlimb was detected as early as 3 days and reached a peak at 7 days after surgery. The temporal change of focal tracer uptake was positively correlated with the pattern of vascular density. Moreover, vascular endothelial growth factor (VEGF) treatment increased the tracer uptake and enhanced angiogenesis, which is consistent with integrin \u03b23 expression. Conclusions: PET imaging of a one-step labeled tracer 18F-PRGD2 targeted to \u03b1v\u03b23 integrin allows longitudinal monitoring of ischemia-induced angiogenesis and noninvasive assessment of VEGF treatment response in a mouse model of hindlimb ischemia. The simple synthesis procedure and in vivo performance of this PET tracer enables the feasibility of future clinical translation in ischemic cardiovascular diseases.<\/jats:p>","DOI":"10.31083\/j.rcm2312408","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T09:06:44Z","timestamp":1671181604000},"source":"Crossref","is-referenced-by-count":0,"title":["Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET"],"prefix":"10.31083","volume":"23","author":[{"given":"Zhongchan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibin","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Tong","sequence":"first","affiliation":[{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Department of Cardiac Surgery, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junqing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"He","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Guangdong Cardiovascular Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China"},{"name":"Department of Cardiology, Heyuan People\u2019s Hospital, 517000 Heyuan, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref1","unstructured":"Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al. 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