Molecular imaging has assumed enormous importance, alongside structural and functional imaging, in the clinical evaluation of new cancer drugs, through the use of imaging biomarkers for selection of patients most likely to respond to specific drugs, and for early detection of response to treatment with the aim of accelerating the measurement of endpoints (e.g., by replacing patient survival and clinical endpoints with early measurement of responses i.e. glucose metabolism or DNA synthesis in tumours). Imaging as a core-technology provides the ability to detect and measure molecular processes and their effects in humans via: [i] real time monitoring, [ii] accessibility without tissue destruction, [iii] low invasiveness, [iv] multiple time points over wide ranges of time scales and [v] multiscale information i.e. from nanoscopic to microscopic to macroscopic, and from molecular to cellular to organ system to complete organism.
Within the department we are developing novel chemistry platforms applicable to both a range of cancer specific molecules and contrast labels (metal and non-metal, for PET, SPECT, MRI and/or optical), while at the same time optimising existing molecular imaging approaches. We are also developing novel delivery technologies applicable to the targeted delivery of MRI contrast agents, radionuclides, genetic material, or small molecule therapeutics, either singly or combined. Such approaches allow us to use these novel molecular imaging concepts and molecular probes for PET, SPECT, MR and optical imaging of novel cancer molecular targets, feeding the “translational pipeline” towards clinical oncology.
Imaging cancer with radiolabelled IgE
Within the department we are developing a number of molecular and cellular strategies for the non-invasive imaging of cancer. We are exploiting the potentially superior migratory and effector function of IgE for the targeting and treatment of cancers. Preclinical studies are currently being performed with radiolabelled IgE alongside its IgG analogue and comparing the rate and extent of accumulation in tumour, and its prolonged residence over ~14 days. Should such a strategy proove successful it will be rapidly evaluated in the clinic.
Imaging of cancer immunotherapy
Cancers can also be targeted adopting a cellular therapy strategy where by immune cells are manipulated to detect and kill cancer cells. The in vivo fate of such immune cells (e.g. T-cells) targeted towards solid tumours is unknown. The ability to track migration, distribution and function of T-cells non-invasively following adoptive transfer would provide early and direct evidence of efficacy. To study homing and survival of gene-modified T-cells, cells will be labelled with MR contrast, PET and/or SPECT radiotracers, for short term tracking (<14 days). The viability and function of radiolabelled T-cells has been thoroughly investigated. Preclinical imaging studies of the radiolabelled anti-cancer T-cells is being performed in a tumor antigen-expressing xenograft mouse model and used to determine the biodistribution and kinetics of tumour targeting. For longitudinal imaging over longer periods, further manipulation to incorporate reporter genes hNIS and GFP is being used. This allows repeated imaging at intervals, while reducing radiation dose absorbed by radiosensitive gene-modified T-cells because short half-life tracers (F-18, Tc-99m) or MR can be used without pre-labelling with large amounts of radioisotope or SPIO.
Regions of hypoxia are a common feature of many human cancers. Much work on tumour hypoxia has focused on cervical, head & neck and lung cancers, but although only a small number of studies have reported on colorectal cancer, nearly all have shown significant hypoxic fractions. Hypoxic cells are resistant to radiotherapy, and hypoxia is a determinant of relapse-free survival and clinical outcome independent of treatment modality, implying that hypoxia is associated with a more aggressive tumour phenotype. Clinicalevaluation of the hypoxia tracer Cu-64-ATSM alongside MR and histopathology is in progress at UCL in head and neck cancer. New methods are being developed and new tracers analogous to CuATSM are being produced and evaluated preclinically at KCL.