Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET
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 αvβ3 integrin are promising tracers for imaging angiogenesis. In this...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2022-12-01
|
| Series: | Reviews in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/RCM/23/12/10.31083/j.rcm2312408 |
| _version_ | 1797975801047547904 |
|---|---|
| author | Zhongchan Sun Weibin He Shuang Xia Guang Tong Lin Zeng Ling Xue Junqing Yang Ning Tan Pengcheng He |
| author_facet | Zhongchan Sun Weibin He Shuang Xia Guang Tong Lin Zeng Ling Xue Junqing Yang Ning Tan Pengcheng He |
| author_sort | Zhongchan Sun |
| collection | DOAJ |
| description | 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 αvβ3 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 αvβ3 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 αvβ3 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 β3 expression. Conclusions: PET imaging of a one-step labeled tracer 18F-PRGD2 targeted to αvβ3integrin 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. |
| first_indexed | 2024-04-11T04:41:12Z |
| format | Article |
| id | doaj.art-52a36bc0725041a7a834daf61d8452fa |
| institution | Directory Open Access Journal |
| issn | 1530-6550 |
| language | English |
| last_indexed | 2024-04-11T04:41:12Z |
| publishDate | 2022-12-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Reviews in Cardiovascular Medicine |
| spelling | doaj.art-52a36bc0725041a7a834daf61d8452fa2022-12-28T05:34:20ZengIMR PressReviews in Cardiovascular Medicine1530-65502022-12-01231240810.31083/j.rcm2312408S1530-6550(22)00743-8Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PETZhongchan Sun0Weibin He1Shuang Xia2Guang Tong3Lin Zeng4Ling Xue5Junqing Yang6Ning Tan7Pengcheng He8Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaGuangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaDepartment of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, ChinaBackground: 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 αvβ3 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 αvβ3 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 αvβ3 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 β3 expression. Conclusions: PET imaging of a one-step labeled tracer 18F-PRGD2 targeted to αvβ3integrin 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.https://www.imrpress.com/journal/RCM/23/12/10.31083/j.rcm2312408angiogenesispet imagingperipheral arterial diseasehindlimb ischemiaintegrinrgd peptide |
| spellingShingle | Zhongchan Sun Weibin He Shuang Xia Guang Tong Lin Zeng Ling Xue Junqing Yang Ning Tan Pengcheng He Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET Reviews in Cardiovascular Medicine angiogenesis pet imaging peripheral arterial disease hindlimb ischemia integrin rgd peptide |
| title | Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET |
| title_full | Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET |
| title_fullStr | Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET |
| title_full_unstemmed | Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET |
| title_short | Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET |
| title_sort | noninvasive evaluation of angiogenesis and therapeutic response after hindlimb ischemia with an integrin targeted tracer by pet |
| topic | angiogenesis pet imaging peripheral arterial disease hindlimb ischemia integrin rgd peptide |
| url | https://www.imrpress.com/journal/RCM/23/12/10.31083/j.rcm2312408 |
| work_keys_str_mv | AT zhongchansun noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT weibinhe noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT shuangxia noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT guangtong noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT linzeng noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT lingxue noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT junqingyang noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT ningtan noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet AT pengchenghe noninvasiveevaluationofangiogenesisandtherapeuticresponseafterhindlimbischemiawithanintegrintargetedtracerbypet |