Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rinne, Sara S., Dahlsson Leitao, Charles, Saleh-nihad, Zahra, Mitran, Bogdan, Tolmachev, Vladimir, Ståhl, Stefan, Löfblom, John, Orlova, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783518873082920960
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
work_keys_str_mv AT rinnesaras benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT dahlssonleitaocharles benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT salehnihadzahra benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT mitranbogdan benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT tolmachevvladimir benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT stahlstefan benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT lofblomjohn benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules
AT orlovaanna benefitoflatertimepointpetimagingofher3expressionusingoptimizedradiocobaltlabeledaffibodymolecules