Pre-clinical imaging core facility

IVIS 200 and IVIS lumina imaging systems (Caliper Lifesciences) are available for whole-animal in vivo photonic imaging. These can perform sensitive and relatively high-throughput in vivo bioluminescence imaging. Typical scans take less than one minute and up to five subjects can be imaged at a time. Fluorescence imaging can also be performed in vivo, although this approach is less sensitive.

MRI

The unit has two Varian MRI systems; a 9.4T with higher sensitivity, and a 7T whose smaller susceptibility effects make it more suitable for techniques such as echo-planar imaging. Both perform 1H MRI and multi-nuclear MRS, assisted by integrated monitoring, gating heating and anaesthesia. We have produced DCE-MRI data for vascular characterisation of tumour models, notably autochthonous pancreatic tumours (Tuveson laboratory). We have implemented improved 1H MRS methods that minimise chemical shift artefacts and we are developing quantitative MT-MRI and motion-insensitive DW-MRI methods for abdominal tumours, which are subject to respiratory and cardiac motion. The unit is currently being refitted to support in vivo hyperpolarised 13C spectroscopy, using a Hypersense system.

Radiotracer methods

A NanoPET/SPECT/CT (Mediso/Bioscan/Philips) system for multimodality radionuclide imaging was installed in 2010. This offers the greatest sensitivity of any in vivo imaging modality and can provide non-invasive assessment of pharmacological (target tissue exposure, target engagement and functional activity) and biological processes (blood flow, perfusion and metabolism). These scanners can resolve at nanolitre resolution (~0.4mm for SPECT and ~1mm for PET) and so are ideal for small animal imaging.

Static and dynamic imaging can be implemented, with or without respiratory/cardiac gating. We can label biologically active molecules with positron emitters and perform kinetic modelling. A PET/CT/SPECT/MRI compatible animal bed system delivers gaseous anaesthesia, maintains body temperature and allows precise co-registration across imaging modalities. Simultaneous dual isotope studies are possible using nanoSPECT and we are investigating multimodality imaging approaches for the integrated molecular imaging of cancer.

Installation of a 68Ga generator will take place in 2011. We are establishing a laboratory for radiolabelling with 68Ga and SPECT radionuclides in collaboration with the radiopharmacy and PET/CT facility at Addenbrooke's Hospital.

Molecular imaging probes currently available for PET include [18F]FDG, [18F]FLT, [18F] FMISO. Preliminary collaborative projects with CRI laboratories will focus on novel molecular marker development and use of PET and SPECT to measure early response of tumours to therapy. The Brindle laboratory are investigating the C2A domain of synaptotagmin, labelled with 111In for SPECT and 64Cu for PET, as a novel probe for detection of tumour cell apoptosis post treatment and the use of [11C]acetate for early detection of malignant transformation. The Tuveson laboratory plan to compare the sensitivity of FDG and FLT to measure pancreatic tumour responses to novel therapeutic protocols.

Metabolomics

The facility is based on a Bruker 600MHz NMR instrument. Ongoing collaborative projects include studies on cellular senescence (Narita laboratory), correlations of epigenetic markers with metabolomics (Murrell laboratory), monitoring response to treatment (Neal laboratory) and 19F NMR of anticancer drug metabolites (Tuveson laboratory). Metabolite correlation methods are being developed, with the Tavaré laboratory, to help interpret the biochemical data.

Facility manager
Kevin Brindle and John Griffiths are joint heads for the Pre-clinical imaging core facility.