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Multimodality Imaging of Apoptosis

S Valleggi, JC Bamber; in collaboration with N deSouza, G Payne, S Robinson, Department of Radiology, Royal Marsden NHS Foundation Trust, and CRUK-EPSRC Cancer Imaging Centre.

Source of funding: CRUK, EPSRC

The iatrogenic induction of apoptosis by radiation or chemotherapy is the “leitmotif” of cancer therapeutics. It is therefore important to be able to non-invasively detect and serially monitor this process in patients undergoing treatment. Imaging is currently used to evaluate tumour shrinkage but this occurs as a late consequence of cell death. 

Use of imaging techniques to non-invasively assess the entire tumour for drug-induced apoptosis at an early time point would be invaluable in the evaluation of novel therapeutics. Research is underway in many centres to develop new imaging methods that monitor apoptosis, but their readouts are each based on a single imaging variable associated with a particular cellular metabolic, membrane or morphological change. Such single imaging variables are not likely to be very specific, and would usually be transiently present for only a limited time after treatment (Figure 15). 

This new project aims to test the hypothesis that a multimodality, multivariate approach will increase the specificity and sensitivity for detecting early apoptosis, particularly in a situation of heterogeneous response, as occurs in the clinical setting, and to determine the best combination of apoptosis imaging variables and methods for broad clinical applicability.

Fig.15.  The time progression of events following induction of apoptosis with indications of potential apoptotic non-invasive imaging markers associated with cell metabolism, cell surface receptors, and cell morphology, as well as the time periods during which different imaging methods may be able to access these markers. Key: OI=optical imaging, PAS=photoacoustic spectroscopy, PET=positron emission tomography, SPECT=single photon emission tomography, DWI=diffusion weighted imaging, MRS=magnetic resonance spectroscopy, MRI=(proton)magnetic resonance imaging, US=ultrasound(backscatter spectroscopy), OCT=optical coherence tomography. (diagram modified from the original on the St George's University of London website)