dc.contributor.author | Papaevangelou, E | |
dc.contributor.author | Almeida, GS | |
dc.contributor.author | Jamin, Y | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | deSouza, NM | |
dc.date.accessioned | 2020-07-28T13:30:38Z | |
dc.date.issued | 2015-04-28 | |
dc.identifier.citation | British journal of cancer, 2015, 112 (9), pp. 1471 - 1479 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3880 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2015.134 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 1471 - 1479 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Tumor Cells, Cultured | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Mice, Nude | |
dc.subject | Adenocarcinoma | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Lymphatic Metastasis | |
dc.subject | Necrosis | |
dc.subject | Camptothecin | |
dc.subject | Indoles | |
dc.subject | Dipeptides | |
dc.subject | Antineoplastic Agents, Phytogenic | |
dc.subject | Diffusion Magnetic Resonance Imaging | |
dc.subject | Blotting, Western | |
dc.subject | Immunoenzyme Techniques | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Apoptosis | |
dc.subject | Cell Proliferation | |
dc.subject | Female | |
dc.subject | Irinotecan | |
dc.title | Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-03-17 | |
rioxxterms.versionofrecord | 10.1038/bjc.2015.134 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
rioxxterms.licenseref.startdate | 2015-04-16 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 9 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 112 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Magnetic Resonance | |
icr.researchteam | Pre-Clinical MRI | |
dc.contributor.icrauthor | Jamin, Yann | |
dc.contributor.icrauthor | Robinson, Simon | |
dc.contributor.icrauthor | deSouza, Nandita | |