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Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)

Integrin α(ν)β(6) promotes migration and invasion of cancer cells, and its overexpression often correlates with poor survival. Therefore, targeting α(ν)β(6) with radioactive peptides would be beneficial for cancer imaging and therapy. Previous studies have successfully developed radiotracers based o...

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Autores principales: Huynh, Truc Thao, Sreekumar, Sreeja, Mpoy, Cedric, Rogers, Buck Edward
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876964/
https://www.ncbi.nlm.nih.gov/pubmed/35215341
http://dx.doi.org/10.3390/ph15020229
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author Huynh, Truc Thao
Sreekumar, Sreeja
Mpoy, Cedric
Rogers, Buck Edward
author_facet Huynh, Truc Thao
Sreekumar, Sreeja
Mpoy, Cedric
Rogers, Buck Edward
author_sort Huynh, Truc Thao
collection PubMed
description Integrin α(ν)β(6) promotes migration and invasion of cancer cells, and its overexpression often correlates with poor survival. Therefore, targeting α(ν)β(6) with radioactive peptides would be beneficial for cancer imaging and therapy. Previous studies have successfully developed radiotracers based on the peptide A20FMDV2 that showed good binding specificity for α(ν)β(6). However, one concern of these α(ν)β(6) integrin-targeting probes is that their rapid blood clearance and low tumor uptake would preclude them from being used for therapeutic purposes. In this study, albumin binders were used to increase tumor uptake for therapeutic applications while the non-albumin peptide was evaluated as a potential positron emission tomography (PET) imaging agent. All peptides used the DOTA chelator for radiolabeling with either (68)Ga for imaging or (177)Lu for therapy. PET imaging with [(68)Ga]Ga-DOTA-(PEG28)(2)-A20FMDV2 revealed specific tumor uptake in α(ν)β(6)-positive tumors. Albumin-binding peptides EB-DOTA-(PEG28)(2)-A20FMDV2 and IBA-DOTA-(PEG28)(2)-A20FMDV2 were radiolabeled with (177)Lu. Biodistribution studies in normal mice showed longer blood circulation times for the albumin binding peptides compared to the non-albumin peptide. Therapy studies in mice demonstrated that both (177)Lu-labeled albumin binding peptides resulted in significant tumor growth inhibition. We believe these are the first studies to demonstrate the therapeutic efficacy of a radiolabeled peptide targeting an α(ν)β(6)-positive tumor.
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spelling pubmed-88769642022-02-26 Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6) Huynh, Truc Thao Sreekumar, Sreeja Mpoy, Cedric Rogers, Buck Edward Pharmaceuticals (Basel) Article Integrin α(ν)β(6) promotes migration and invasion of cancer cells, and its overexpression often correlates with poor survival. Therefore, targeting α(ν)β(6) with radioactive peptides would be beneficial for cancer imaging and therapy. Previous studies have successfully developed radiotracers based on the peptide A20FMDV2 that showed good binding specificity for α(ν)β(6). However, one concern of these α(ν)β(6) integrin-targeting probes is that their rapid blood clearance and low tumor uptake would preclude them from being used for therapeutic purposes. In this study, albumin binders were used to increase tumor uptake for therapeutic applications while the non-albumin peptide was evaluated as a potential positron emission tomography (PET) imaging agent. All peptides used the DOTA chelator for radiolabeling with either (68)Ga for imaging or (177)Lu for therapy. PET imaging with [(68)Ga]Ga-DOTA-(PEG28)(2)-A20FMDV2 revealed specific tumor uptake in α(ν)β(6)-positive tumors. Albumin-binding peptides EB-DOTA-(PEG28)(2)-A20FMDV2 and IBA-DOTA-(PEG28)(2)-A20FMDV2 were radiolabeled with (177)Lu. Biodistribution studies in normal mice showed longer blood circulation times for the albumin binding peptides compared to the non-albumin peptide. Therapy studies in mice demonstrated that both (177)Lu-labeled albumin binding peptides resulted in significant tumor growth inhibition. We believe these are the first studies to demonstrate the therapeutic efficacy of a radiolabeled peptide targeting an α(ν)β(6)-positive tumor. MDPI 2022-02-15 /pmc/articles/PMC8876964/ /pubmed/35215341 http://dx.doi.org/10.3390/ph15020229 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huynh, Truc Thao
Sreekumar, Sreeja
Mpoy, Cedric
Rogers, Buck Edward
Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title_full Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title_fullStr Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title_full_unstemmed Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title_short Therapeutic Efficacy of (177)Lu-Labeled A20FMDV2 Peptides Targeting α(ν)β(6)
title_sort therapeutic efficacy of (177)lu-labeled a20fmdv2 peptides targeting α(ν)β(6)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876964/
https://www.ncbi.nlm.nih.gov/pubmed/35215341
http://dx.doi.org/10.3390/ph15020229
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