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Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents

OBJECTIVE: The aim of the present study was to develop potential candidates of integrin αvβ3-targeted imaging agent, which can facilitate the diagnosis and treatment of malignant solid tumors. METHODS: Peptides derived from tumstatin, named T7 and T7-6H, were derivatized to contain histidine in the...

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Autores principales: He, Xin, Hao, Yumei, Long, Wei, Song, Naling, Fan, Saijun, Meng, Aimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474394/
https://www.ncbi.nlm.nih.gov/pubmed/26109872
http://dx.doi.org/10.2147/OTT.S82095
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author He, Xin
Hao, Yumei
Long, Wei
Song, Naling
Fan, Saijun
Meng, Aimin
author_facet He, Xin
Hao, Yumei
Long, Wei
Song, Naling
Fan, Saijun
Meng, Aimin
author_sort He, Xin
collection PubMed
description OBJECTIVE: The aim of the present study was to develop potential candidates of integrin αvβ3-targeted imaging agent, which can facilitate the diagnosis and treatment of malignant solid tumors. METHODS: Peptides derived from tumstatin, named T7 and T7-6H, were derivatized to contain histidine in the C-terminus of their sequence and were labeled with (99m)Tc via nitrido and carbonyl precursors. The radiochemical purity and stability of (99m)Tc-labeled T7 and T7-6H were characterized by thin-layer chromatography. The whole body biodistribution was studied in NCI-H157-bearing BALB/c nude mice. RESULTS: The (99m)Tc-labeled T7 and T7-6H showed adequate in vitro stability, with a high radiochemical purity of over 90%. The dissociation constant (Kd) value of the (99m)Tc-labeled T7 and T7-6H ranged from 68.5 nM to 140.8 nM in U251 and NCI-H157 cell lines. (99m)Tc-labeled T7 and T7-6H showed no significant difference of biodistribution in mice. Furthermore, both T7 and T7-6H exhibited a poor blood–brain barrier penetration and a transient accumulation in lung; the uptake in tumor tissues was significantly higher than in muscle tissue, with a ratio of 5.8. CONCLUSION: (99m)Tc-labeled T7 and T7-6H can be regarded as promising single-photon emission computed tomography probes for imaging integrin αvβ3, and need to be further studied for noninvasive detection of tumors.
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spelling pubmed-44743942015-06-24 Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents He, Xin Hao, Yumei Long, Wei Song, Naling Fan, Saijun Meng, Aimin Onco Targets Ther Original Research OBJECTIVE: The aim of the present study was to develop potential candidates of integrin αvβ3-targeted imaging agent, which can facilitate the diagnosis and treatment of malignant solid tumors. METHODS: Peptides derived from tumstatin, named T7 and T7-6H, were derivatized to contain histidine in the C-terminus of their sequence and were labeled with (99m)Tc via nitrido and carbonyl precursors. The radiochemical purity and stability of (99m)Tc-labeled T7 and T7-6H were characterized by thin-layer chromatography. The whole body biodistribution was studied in NCI-H157-bearing BALB/c nude mice. RESULTS: The (99m)Tc-labeled T7 and T7-6H showed adequate in vitro stability, with a high radiochemical purity of over 90%. The dissociation constant (Kd) value of the (99m)Tc-labeled T7 and T7-6H ranged from 68.5 nM to 140.8 nM in U251 and NCI-H157 cell lines. (99m)Tc-labeled T7 and T7-6H showed no significant difference of biodistribution in mice. Furthermore, both T7 and T7-6H exhibited a poor blood–brain barrier penetration and a transient accumulation in lung; the uptake in tumor tissues was significantly higher than in muscle tissue, with a ratio of 5.8. CONCLUSION: (99m)Tc-labeled T7 and T7-6H can be regarded as promising single-photon emission computed tomography probes for imaging integrin αvβ3, and need to be further studied for noninvasive detection of tumors. Dove Medical Press 2015-06-15 /pmc/articles/PMC4474394/ /pubmed/26109872 http://dx.doi.org/10.2147/OTT.S82095 Text en © 2015 He et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
He, Xin
Hao, Yumei
Long, Wei
Song, Naling
Fan, Saijun
Meng, Aimin
Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title_full Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title_fullStr Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title_full_unstemmed Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title_short Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents
title_sort exploration of peptide t7 and its derivative as integrin αvβ3-targeted imaging agents
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474394/
https://www.ncbi.nlm.nih.gov/pubmed/26109872
http://dx.doi.org/10.2147/OTT.S82095
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