Apparent diffusion coefficient from magnetic resonance imaging as a biomarker in oncology drug development

Abstract Magnetic resonance imaging (MRI) can be made sensitive to diffusion of water molecules in biological tissues: this phenomenon can be quantitated to provide a biomarker, the apparent diffusion coefficient (ADC). Over the past decade, evidence has accumulated from numerous clinical and animal...

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Bibliographic Details
Published in:European journal of cancer (1990) 2012-03, Vol.48 (4), p.425-431
Main Authors: Sinkus, Ralph, Van Beers, Bernard E, Vilgrain, Valérie, DeSouza, Nandita, Waterton, John C
Format: Article
Language:English
Subjects:
ADC
Biomarkers, Pharmacological - analysis
Biomarkers, Tumor - analysis
Cell membrane integrity
Diffusion
Diffusion Magnetic Resonance Imaging - methods
Diffusion Magnetic Resonance Imaging - standards
Diffusion Magnetic Resonance Imaging - statistics & numerical data
Diffusion Magnetic Resonance Imaging - utilization
Diffusion weighted MRI
Drug Discovery - methods
Hematology, Oncology and Palliative Medicine
Humans
Medical Oncology - methods
Medical Oncology - standards
Neoplasms - diagnosis
Neoplasms - drug therapy
Prognosis
Tumor response
Validation Studies as Topic
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Summary:Abstract Magnetic resonance imaging (MRI) can be made sensitive to diffusion of water molecules in biological tissues: this phenomenon can be quantitated to provide a biomarker, the apparent diffusion coefficient (ADC). Over the past decade, evidence has accumulated from numerous clinical and animal studies that ADC is abnormal in tumours; that elevated ADC reflects an elevated non-cellular fraction; and that acute increases in ADC following therapy can indicate that tumour cells have been killed. However there remain substantial challenges in ensuring robust and valid ADC measurements, particularly in multicentre studies in common sites of metastasis such as lung and liver. Moreover, there is uncertainty about how best to select the timing of observation post-therapy to avoid false-negatives, and how to minimise the confounding factors which could decouple drug-induced ADC increase from drug-induced cell kill. In this review we summarise the physical basis of the biomarker, the evidence that it reflects non-viable fraction, particularly in extracranial tumours, and suggest a roadmap for validation and qualification.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2011.11.034