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dc.contributor.authorPapaevangelou, E
dc.contributor.authorAlmeida, GS
dc.contributor.authorJamin, Y
dc.contributor.authorRobinson, SP
dc.contributor.authordeSouza, NM
dc.date.accessioned2020-07-28T13:30:38Z
dc.date.issued2015-04-16
dc.identifier.citationBritish journal of cancer, 2015, 112 (9), pp. 1471 - 1479
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3880
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2015.134
dc.description.abstractBackground Non-invasive serial imaging is desirable to detect processes such as necrotic and apoptotic cell death in cancer patients undergoing treatment. This study investigated the use of diffusion-weighted (DW-) magnetic resonance imaging (MRI) for imaging cell death induced by either a cytotoxic drug (irinotecan), or the apoptosis-inducing agent birinapant, in human tumour xenografts in vivo.Methods Nude mice bearing human SW620 colon carcinoma xenografts were treated with vehicle, irinotecan (50 mg kg(-1)) or birinapant (30 mg kg(-1)) for up to 5 days. DW-MRI was performed prior to and on days 1, 3 and 5 during treatment. Assessment of tumour apoptosis and necrosis ex vivo was used to validate the imaging findings.Results Both irinotecan and birinapant induced significant tumour growth delay. Irinotecan induced a small increase in the tumour apparent diffusion coefficient (ADC) after 1 day, with a 20 and 30% increase at days 3 and 5 respectively. ADC was unchanged in the vehicle- and birinapant-treated tumours despite a growth delay in the latter. Histological analysis showed that irinotecan increased necrosis at days 3 and 5, and induced apoptosis after 1 day, compared with vehicle. Birinapant induced apoptosis after day 3, but had no effect on tumour necrosis.Conclusions Tumour ADC changes after irinotecan treatment were associated with the induction of a mixture of necrotic and apoptotic cell death, whereas induction of apoptosis alone with birinapant was not sufficient to induce changes in tissue microstructure that were detectable with DW-MRI. ADC is a useful non-invasive biomarker for early detection of response to cytotoxic drugs, but false negatives may arise while detecting apoptotic response to birinapant.
dc.formatPrint-Electronic
dc.format.extent1471 - 1479
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectTumor Cells, Cultured
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectAdenocarcinoma
dc.subjectColorectal Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectNecrosis
dc.subjectCamptothecin
dc.subjectIndoles
dc.subjectDipeptides
dc.subjectAntineoplastic Agents, Phytogenic
dc.subjectDiffusion Magnetic Resonance Imaging
dc.subjectBlotting, Western
dc.subjectImmunoenzyme Techniques
dc.subjectXenograft Model Antitumor Assays
dc.subjectApoptosis
dc.subjectCell Proliferation
dc.subjectFemale
dc.subjectIrinotecan
dc.titleDiffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy.
dc.typeJournal Article
dcterms.dateAccepted2015-03-17
rioxxterms.versionofrecord10.1038/bjc.2015.134
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
rioxxterms.licenseref.startdate2015-04-16
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue9
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume112
pubs.embargo.termsNot known
icr.researchteamMagnetic Resonanceen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorJamin, Yannen
dc.contributor.icrauthordeSouza, Nanditaen
dc.contributor.icrauthorRobinson, Simonen


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