Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging

Abstract Anti-angiogenesis has been recognized as a crucial strategy in anti-tumor therapy, and the early assessment of its efficacy is equally significant. In this study, we developed a magnetic resonance (MR) probe specifically targeting angiogenesis to facilitate targeted imaging for the early ev...

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Main Authors: Sheng Han, Song-Song Liu, Gong-Wei Jing, Pin-Qin Wang, Yan-Teng Zhang, Ling Xiong, Ying-Fang Zhang, Hua-Sheng Qu, Bing-Xiu Ren
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05905-1
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author Sheng Han
Song-Song Liu
Gong-Wei Jing
Pin-Qin Wang
Yan-Teng Zhang
Ling Xiong
Ying-Fang Zhang
Hua-Sheng Qu
Bing-Xiu Ren
author_facet Sheng Han
Song-Song Liu
Gong-Wei Jing
Pin-Qin Wang
Yan-Teng Zhang
Ling Xiong
Ying-Fang Zhang
Hua-Sheng Qu
Bing-Xiu Ren
author_sort Sheng Han
collection DOAJ
description Abstract Anti-angiogenesis has been recognized as a crucial strategy in anti-tumor therapy, and the early assessment of its efficacy is equally significant. In this study, we developed a magnetic resonance (MR) probe specifically targeting angiogenesis to facilitate targeted imaging for the early evaluation of anti-angiogenic effects. We synthesized DOTA-G3CNGRC, conjugated it with gadolinium(III), and subsequently evaluated the labeled probe in vitro. The tumor-bearing mouse models of HT-29 (negative for CD13 expression) and HT-1080 (positive for CD13 expression) were successfully established. Magnetic resonance imaging was conducted via intraperitoneal injection of labeled probes and Gd-DOTA, both before and after treatment with ubenimex at a dose of 0.5 mg/kg/day for seven consecutive days. The average signal intensity ratio of the transplanted tumor (target tissue, T) to the left hind leg (non-target tissue, NT) was determined using the region of interest technique (ROI), while changes in tumor size were meticulously recorded. Additionally, APN/CD13 expression levels in transplanted tumors were assessed both prior to and following treatment. The labeling rate of probes was 88.99%. The IC50 of the probes was 7.03 µM. The T/NT ratio of HT-1080 was significantly higher than that of HT-29 (P < 0.001, n = 5). Following treatment, the T/NT ratio of the HT-1080 transplanted tumors was significantly reduced (P < 0.001, n = 5), accompanied by a notable decrease in CD13 expression and negligible changes in the sum of the long and short diameters (P = 0.39, n = 5). The research findings revealed that Gd-DOTA-G3CNGRC can serve as a highly specific gadolinium-based magnetic resonance imaging probe for monitoring the efficacy of anti-angiogenic therapy.
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spelling doaj-art-afdf106295574eed97919c508c8a39b62025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-05905-1Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imagingSheng Han0Song-Song Liu1Gong-Wei Jing2Pin-Qin Wang3Yan-Teng Zhang4Ling Xiong5Ying-Fang Zhang6Hua-Sheng Qu7Bing-Xiu Ren8Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Radiology, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Radiology, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi City)Abstract Anti-angiogenesis has been recognized as a crucial strategy in anti-tumor therapy, and the early assessment of its efficacy is equally significant. In this study, we developed a magnetic resonance (MR) probe specifically targeting angiogenesis to facilitate targeted imaging for the early evaluation of anti-angiogenic effects. We synthesized DOTA-G3CNGRC, conjugated it with gadolinium(III), and subsequently evaluated the labeled probe in vitro. The tumor-bearing mouse models of HT-29 (negative for CD13 expression) and HT-1080 (positive for CD13 expression) were successfully established. Magnetic resonance imaging was conducted via intraperitoneal injection of labeled probes and Gd-DOTA, both before and after treatment with ubenimex at a dose of 0.5 mg/kg/day for seven consecutive days. The average signal intensity ratio of the transplanted tumor (target tissue, T) to the left hind leg (non-target tissue, NT) was determined using the region of interest technique (ROI), while changes in tumor size were meticulously recorded. Additionally, APN/CD13 expression levels in transplanted tumors were assessed both prior to and following treatment. The labeling rate of probes was 88.99%. The IC50 of the probes was 7.03 µM. The T/NT ratio of HT-1080 was significantly higher than that of HT-29 (P < 0.001, n = 5). Following treatment, the T/NT ratio of the HT-1080 transplanted tumors was significantly reduced (P < 0.001, n = 5), accompanied by a notable decrease in CD13 expression and negligible changes in the sum of the long and short diameters (P = 0.39, n = 5). The research findings revealed that Gd-DOTA-G3CNGRC can serve as a highly specific gadolinium-based magnetic resonance imaging probe for monitoring the efficacy of anti-angiogenic therapy.https://doi.org/10.1038/s41598-025-05905-1APN/CD13AngiogenesisAnti-angiogenesisAsn-Gly-Arg (NGR) peptideGadolinium(III)
spellingShingle Sheng Han
Song-Song Liu
Gong-Wei Jing
Pin-Qin Wang
Yan-Teng Zhang
Ling Xiong
Ying-Fang Zhang
Hua-Sheng Qu
Bing-Xiu Ren
Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
Scientific Reports
APN/CD13
Angiogenesis
Anti-angiogenesis
Asn-Gly-Arg (NGR) peptide
Gadolinium(III)
title Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
title_full Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
title_fullStr Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
title_full_unstemmed Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
title_short Early evaluation of anti-angiogenic effects with gadolinium(III) labeled APN/CD13 specific binding peptides magnetic resonance imaging
title_sort early evaluation of anti angiogenic effects with gadolinium iii labeled apn cd13 specific binding peptides magnetic resonance imaging
topic APN/CD13
Angiogenesis
Anti-angiogenesis
Asn-Gly-Arg (NGR) peptide
Gadolinium(III)
url https://doi.org/10.1038/s41598-025-05905-1
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