Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy.
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Date
2015-04-28Author
Papaevangelou, E
Almeida, GS
Jamin, Y
Robinson, SP
deSouza, NM
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Tumor Cells, Cultured
Animals
Humans
Mice
Mice, Nude
Adenocarcinoma
Colorectal Neoplasms
Lymphatic Metastasis
Necrosis
Camptothecin
Indoles
Dipeptides
Antineoplastic Agents, Phytogenic
Diffusion Magnetic Resonance Imaging
Blotting, Western
Immunoenzyme Techniques
Xenograft Model Antitumor Assays
Apoptosis
Cell Proliferation
Female
Irinotecan
Research team
Magnetic Resonance
Pre-Clinical MRI
Language
eng
Date accepted
2015-03-17
License start date
2015-04-16
Citation
British journal of cancer, 2015, 112 (9), pp. 1471 - 1479
Publisher
NATURE PUBLISHING GROUP