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Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()

While radiolabelled antibodies have found great utility as PET and SPECT imaging agents in oncological investigations, a notable shortcoming of these agents is their propensity to accumulate non-specifically within tumour tissue. The degree of this non-specific contribution to overall tumour uptake...

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Autores principales: Knight, James C., Mosley, Michael J., Kersemans, Veerle, Dias, Gemma M., Allen, P. Danny, Smart, Sean, Cornelissen, Bart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599172/
https://www.ncbi.nlm.nih.gov/pubmed/30825614
http://dx.doi.org/10.1016/j.nucmedbio.2019.01.010
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author Knight, James C.
Mosley, Michael J.
Kersemans, Veerle
Dias, Gemma M.
Allen, P. Danny
Smart, Sean
Cornelissen, Bart
author_facet Knight, James C.
Mosley, Michael J.
Kersemans, Veerle
Dias, Gemma M.
Allen, P. Danny
Smart, Sean
Cornelissen, Bart
author_sort Knight, James C.
collection PubMed
description While radiolabelled antibodies have found great utility as PET and SPECT imaging agents in oncological investigations, a notable shortcoming of these agents is their propensity to accumulate non-specifically within tumour tissue. The degree of this non-specific contribution to overall tumour uptake is highly variable and can ultimately lead to false conclusions. Therefore, in an effort to obtain a reliable measure of inter-individual differences in non-specific tumour uptake of radiolabelled antibodies, we demonstrate that the use of dual-isotope imaging overcomes this issue, enables true quantification of epitope expression levels, and allows non-invasive in vivo immunohistochemistry. The approach involves co-administration of (i) an antigen-targeting antibody labelled with zirconium-89 ((89)Zr), and (ii) an isotype-matched non-specific control IgG antibody labelled with indium-111 ((111)In). As an example, the anti-HER2 antibody trastuzumab was radiolabelled with (89)Zr, and co-administered intravenously together with its (111)In-labelled non-specific counterpart to mice bearing human breast cancer xenografts with differing HER2 expression levels (MDA-MB-468 [HER2-negative], MDA-MB-231 [low-HER2], MDA-MB-231/H2N [medium-HER2], and SKBR3 [high-HER2]). Simultaneous PET/SPECT imaging using a MILabs Vector4 small animal scanner revealed stark differences in the intratumoural distribution of [(89)Zr]Zr-trastuzumab and [(111)In]In-IgG, highlighting regions of HER2-mediated uptake and non-specific uptake, respectively. Normalisation of the tumour uptake values and tumour-to-blood ratios obtained with [(89)Zr]Zr-trastuzumab against those obtained with [(111)In]In-IgG yielded values which were most strongly correlated (R = 0.94; P = 0.02) with HER2 expression levels for each breast cancer type determined by Western blot and in vitro saturation binding assays, but not non-normalised uptake values. Normalised intratumoural distribution of [(89)Zr]Zr-trastuzumab correlated well with intratumoural heterogeneity HER2 expression.
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spelling pubmed-65991722019-07-11 Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()() Knight, James C. Mosley, Michael J. Kersemans, Veerle Dias, Gemma M. Allen, P. Danny Smart, Sean Cornelissen, Bart Nucl Med Biol Article While radiolabelled antibodies have found great utility as PET and SPECT imaging agents in oncological investigations, a notable shortcoming of these agents is their propensity to accumulate non-specifically within tumour tissue. The degree of this non-specific contribution to overall tumour uptake is highly variable and can ultimately lead to false conclusions. Therefore, in an effort to obtain a reliable measure of inter-individual differences in non-specific tumour uptake of radiolabelled antibodies, we demonstrate that the use of dual-isotope imaging overcomes this issue, enables true quantification of epitope expression levels, and allows non-invasive in vivo immunohistochemistry. The approach involves co-administration of (i) an antigen-targeting antibody labelled with zirconium-89 ((89)Zr), and (ii) an isotype-matched non-specific control IgG antibody labelled with indium-111 ((111)In). As an example, the anti-HER2 antibody trastuzumab was radiolabelled with (89)Zr, and co-administered intravenously together with its (111)In-labelled non-specific counterpart to mice bearing human breast cancer xenografts with differing HER2 expression levels (MDA-MB-468 [HER2-negative], MDA-MB-231 [low-HER2], MDA-MB-231/H2N [medium-HER2], and SKBR3 [high-HER2]). Simultaneous PET/SPECT imaging using a MILabs Vector4 small animal scanner revealed stark differences in the intratumoural distribution of [(89)Zr]Zr-trastuzumab and [(111)In]In-IgG, highlighting regions of HER2-mediated uptake and non-specific uptake, respectively. Normalisation of the tumour uptake values and tumour-to-blood ratios obtained with [(89)Zr]Zr-trastuzumab against those obtained with [(111)In]In-IgG yielded values which were most strongly correlated (R = 0.94; P = 0.02) with HER2 expression levels for each breast cancer type determined by Western blot and in vitro saturation binding assays, but not non-normalised uptake values. Normalised intratumoural distribution of [(89)Zr]Zr-trastuzumab correlated well with intratumoural heterogeneity HER2 expression. Elsevier 2019-03 /pmc/articles/PMC6599172/ /pubmed/30825614 http://dx.doi.org/10.1016/j.nucmedbio.2019.01.010 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Knight, James C.
Mosley, Michael J.
Kersemans, Veerle
Dias, Gemma M.
Allen, P. Danny
Smart, Sean
Cornelissen, Bart
Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title_full Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title_fullStr Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title_full_unstemmed Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title_short Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
title_sort dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours()()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599172/
https://www.ncbi.nlm.nih.gov/pubmed/30825614
http://dx.doi.org/10.1016/j.nucmedbio.2019.01.010
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