Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

The effects of the vascular disrupting agents combretastatin A-4 disodium phosphate, 5,6-dimethylxanthenone-4-acetic acid and ZD6126 in a murine tumour: a comparative assessment using MRI and MRS.

The aim of this study was to use magnetic resonance (MR) techniques to non-invasively compare the effects of the three leading vascular disrupting agents, namely combretastatin A-4 disodium phosphate (CA4DP), 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and ZD6126. A C3H mouse mammary carcinoma grown in the right rear foot of female CDF1 mice was used and treatments performed when tumours had reached 200 mm3 in volume. Drugs were prepared fresh before each experiment and intraperitoneally injected into restrained non-anaesthetised mice. Tumour response was evaluated using 31P-MR spectroscopy and T1- and T2- weighted imaging with a 7-Tesla, horizontal bore magnet, before and up to 24 hours after treatment. All three drugs significantly decreased bioenergetic status and pH, and did so in a time and dose dependent fashion, but there were differences; the decrease by CA4DP occurred more rapidly than for DMXAA or ZD6126, while DMXAA had a narrow window of activity compared to CA4DP and ZD6126. Changes in T1 weighted images for all three agents suggested a dose dependent increase in tumour oedema within three hours after treatment, consistent with an increase in vessel permeability. Using T2 weighted images there was some evidence of haemorrhagic necrosis by DMXAA, but such necrosis was limited following treatment with CA4DP or ZD6126.