In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis

IntroductionIntegrin αvβ6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvβ6 could therefore be valuable for early tumor detection and intraoperative guidance.MethodsIn this stud...

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Main Authors: Di Fan, Chengkai Zhang, Qi Luo, Baowang Li, Lin Ai, Deling Li, Wang Jia
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1070967/full
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author Di Fan
Chengkai Zhang
Qi Luo
Baowang Li
Lin Ai
Deling Li
Wang Jia
author_facet Di Fan
Chengkai Zhang
Qi Luo
Baowang Li
Lin Ai
Deling Li
Wang Jia
author_sort Di Fan
collection DOAJ
description IntroductionIntegrin αvβ6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvβ6 could therefore be valuable for early tumor detection and intraoperative guidance.MethodsIn this study, integrin αvβ6-targeting probe G2-SFLAP3 was labeled with near-infrared (NIR) dye Cy5.5 or radioisotope 68Ga. The resulting probes were evaluated in integrin αvβ6-positive A549 and αvβ6-negative H1703 xenograft mice models.ResultsThe cellar uptake of G2-SFLAP3-Cy5.5 was consistent with the expression of integrin αvβ6. Both subcutaneous and brain metastatic A549 tumors could be clearly visualized by NIR fluorescent imaging of G2-SFLAP3-Cy5.5. A549 tumors demonstrated the highest G2-SFLAP3-Cy5.5 accumulation at 4h post-injection (p.i.) and remain detectable at 84h p.i. The fluorescent signal of G2-SFLAP3-Cy5.5 was significantly reduced in H1703 and A549-blocking groups. Consistently, small-animal PET imaging showed tumor-specific accumulation of 68Ga-DOTA-G2-SFLAP3.DiscussionG2-SFLAP3 represents a promising agent for noninvasive imaging of non-small cell lung cancer (NSCLC) and brain metastases.
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spelling doaj.art-4ad7787a687b45ffa3009165d4ff1a322023-03-10T05:39:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.10709671070967In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasisDi Fan0Chengkai Zhang1Qi Luo2Baowang Li3Lin Ai4Deling Li5Wang Jia6Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaGuangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaIntroductionIntegrin αvβ6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvβ6 could therefore be valuable for early tumor detection and intraoperative guidance.MethodsIn this study, integrin αvβ6-targeting probe G2-SFLAP3 was labeled with near-infrared (NIR) dye Cy5.5 or radioisotope 68Ga. The resulting probes were evaluated in integrin αvβ6-positive A549 and αvβ6-negative H1703 xenograft mice models.ResultsThe cellar uptake of G2-SFLAP3-Cy5.5 was consistent with the expression of integrin αvβ6. Both subcutaneous and brain metastatic A549 tumors could be clearly visualized by NIR fluorescent imaging of G2-SFLAP3-Cy5.5. A549 tumors demonstrated the highest G2-SFLAP3-Cy5.5 accumulation at 4h post-injection (p.i.) and remain detectable at 84h p.i. The fluorescent signal of G2-SFLAP3-Cy5.5 was significantly reduced in H1703 and A549-blocking groups. Consistently, small-animal PET imaging showed tumor-specific accumulation of 68Ga-DOTA-G2-SFLAP3.DiscussionG2-SFLAP3 represents a promising agent for noninvasive imaging of non-small cell lung cancer (NSCLC) and brain metastases.https://www.frontiersin.org/articles/10.3389/fonc.2023.1070967/fullintegrin αvβ6NSCLCbrain metastasesPETnear-infrared fluorescence imaging
spellingShingle Di Fan
Chengkai Zhang
Qi Luo
Baowang Li
Lin Ai
Deling Li
Wang Jia
In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
Frontiers in Oncology
integrin αvβ6
NSCLC
brain metastases
PET
near-infrared fluorescence imaging
title In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
title_full In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
title_fullStr In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
title_full_unstemmed In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
title_short In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis
title_sort in vivo evaluation of integrin αvβ6 targeting peptide in nsclc and brain metastasis
topic integrin αvβ6
NSCLC
brain metastases
PET
near-infrared fluorescence imaging
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1070967/full
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