Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer.

Detalles Bibliográficos
Autores: Alakonya, Hudson, Koustoulidou, Sofia, Hopkins, Samantha L., Veal, Mathew, Ajenjo, Javier, Sneddon, Deborah, Dias, Gemma, Mosley, Michael, Baguña Torres, Júlia, Amoroso, Francesca, Anderson, Amanda, Banham, Alison H., Cornelissen, Bart
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/419982
Acceso en línea:http://hdl.handle.net/10261/419982
Access Level:acceso abierto
Palabra clave:Molecular imaging
p53
Cancer
Pancreatic ductal adenocarcinoma
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spelling Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECTAlakonya, HudsonKoustoulidou, SofiaHopkins, Samantha L.Veal, MathewAjenjo, JavierSneddon, DeborahDias, GemmaMosley, MichaelBaguña Torres, JúliaAmoroso, FrancescaAnderson, AmandaBanham, Alison H.Cornelissen, BartMolecular imagingp53CancerPancreatic ductal adenocarcinomaMutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer.[Methods] Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with 111In to allow SPECT imaging. 111In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific 111In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells.[Results] In vivo SPECT imaging showed enhanced uptake of 111In-anti-p53-TAT, versus 111In-mIgG-TAT, in high-expression p53R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with 111In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53R172H pancreatic ductal adenocarcinoma tumors.[Conclusion] We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.This research was supported by the Medical Research Council (Bart Cornelissen and Sofia Koustoulidou), by Cancer Research U.K. through the Oxford Institute for Radiation Oncology (Bart Cornelissen), by the Medical Research Council (through a DPhil fellowship to Sofia Koustoulidou), and by the Rhodes Trust (through a DPhil studentship to Hudson Alakonya).Peer reviewedSociety of Nuclear Medicine and Molecular ImagingMedical Research Council (UK)Cancer Research UKMedical Research Council (UK)Rhodes Trust202620262024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/419982reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.2967/jnumed.124.267736Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4199822026-05-22T06:33:51Z
dc.title.none.fl_str_mv Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
title Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
spellingShingle Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
Alakonya, Hudson
Molecular imaging
p53
Cancer
Pancreatic ductal adenocarcinoma
title_short Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
title_full Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
title_fullStr Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
title_full_unstemmed Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
title_sort Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT
dc.creator.none.fl_str_mv Alakonya, Hudson
Koustoulidou, Sofia
Hopkins, Samantha L.
Veal, Mathew
Ajenjo, Javier
Sneddon, Deborah
Dias, Gemma
Mosley, Michael
Baguña Torres, Júlia
Amoroso, Francesca
Anderson, Amanda
Banham, Alison H.
Cornelissen, Bart
author Alakonya, Hudson
author_facet Alakonya, Hudson
Koustoulidou, Sofia
Hopkins, Samantha L.
Veal, Mathew
Ajenjo, Javier
Sneddon, Deborah
Dias, Gemma
Mosley, Michael
Baguña Torres, Júlia
Amoroso, Francesca
Anderson, Amanda
Banham, Alison H.
Cornelissen, Bart
author_role author
author2 Koustoulidou, Sofia
Hopkins, Samantha L.
Veal, Mathew
Ajenjo, Javier
Sneddon, Deborah
Dias, Gemma
Mosley, Michael
Baguña Torres, Júlia
Amoroso, Francesca
Anderson, Amanda
Banham, Alison H.
Cornelissen, Bart
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medical Research Council (UK)
Cancer Research UK
Medical Research Council (UK)
Rhodes Trust
dc.subject.none.fl_str_mv Molecular imaging
p53
Cancer
Pancreatic ductal adenocarcinoma
topic Molecular imaging
p53
Cancer
Pancreatic ductal adenocarcinoma
description Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer.
publishDate 2024
dc.date.none.fl_str_mv 2024
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/419982
url http://hdl.handle.net/10261/419982
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.2967/jnumed.124.267736
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Society of Nuclear Medicine and Molecular Imaging
publisher.none.fl_str_mv Society of Nuclear Medicine and Molecular Imaging
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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