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Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules
HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139902/ https://www.ncbi.nlm.nih.gov/pubmed/32183096 http://dx.doi.org/10.3390/ijms21061972 |
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author | Rinne, Sara S. Dahlsson Leitao, Charles Saleh-nihad, Zahra Mitran, Bogdan Tolmachev, Vladimir Ståhl, Stefan Löfblom, John Orlova, Anna |
author_facet | Rinne, Sara S. Dahlsson Leitao, Charles Saleh-nihad, Zahra Mitran, Bogdan Tolmachev, Vladimir Ståhl, Stefan Löfblom, John Orlova, Anna |
author_sort | Rinne, Sara S. |
collection | PubMed |
description | HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)(3)-Z(HER3) and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)(3)-Z(HER3)-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [(57)Co]Co (surrogate for (55)Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA 3 h pi, [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [(57)Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA improved imaging contrast compared to early-time-point imaging with [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA. |
format | Online Article Text |
id | pubmed-7139902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71399022020-04-13 Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules Rinne, Sara S. Dahlsson Leitao, Charles Saleh-nihad, Zahra Mitran, Bogdan Tolmachev, Vladimir Ståhl, Stefan Löfblom, John Orlova, Anna Int J Mol Sci Article HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)(3)-Z(HER3) and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)(3)-Z(HER3)-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [(57)Co]Co (surrogate for (55)Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA 3 h pi, [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [(57)Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [(57)Co]Co-(HE)(3)-Z(HER3)-DOTA improved imaging contrast compared to early-time-point imaging with [(68)Ga]Ga-(HE)(3)-Z(HER3)-NODAGA. MDPI 2020-03-13 /pmc/articles/PMC7139902/ /pubmed/32183096 http://dx.doi.org/10.3390/ijms21061972 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rinne, Sara S. Dahlsson Leitao, Charles Saleh-nihad, Zahra Mitran, Bogdan Tolmachev, Vladimir Ståhl, Stefan Löfblom, John Orlova, Anna Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title | Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title_full | Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title_fullStr | Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title_full_unstemmed | Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title_short | Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules |
title_sort | benefit of later-time-point pet imaging of her3 expression using optimized radiocobalt-labeled affibody molecules |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139902/ https://www.ncbi.nlm.nih.gov/pubmed/32183096 http://dx.doi.org/10.3390/ijms21061972 |
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