Student: Madeleine Iafrate
Over the last decade, cell-based therapies have received considerable attention as novel therapeutics in regenerative medicine, oncology and more recently in immune tolerance. Most trials conducted to date measure clinical end points that may take weeks to months to demonstrate efficacy, with little or no knowledge of the in vivo fate and behaviour of administered cells. The questions “where do the cells go after administration?” “how long do the cells survive in vivo?” “Do they proliferate and differentiate?” are too infrequently asked, or remain difficult to answer, in clinical trials. A cell tracking core technology platform is required that can be used in humans and animal models to more accurately elucidate the in vivo mechanism of action and efficacy of cellular therapies.
Non-invasive PET/CT or SPECT/CT imaging with either exogenous labelling of cells or transfection with a reporter gene can do this, over different timescales from hours to years, by combining direct labelling techniques (using radionuclide, optical or magnetic methods) with reporter gene techniques (also using radionuclide or optical methods). We have recently developed the first long half-life PET radiolabel for cells (Zr-89-oxinate)1 (Fig. 1), the first F-18-labelled PET tracer for the sodium/iodide symporter reporter gene2 and the first combination of the latter with optical reporter genes3 (Fig. 1).
Figure 1: Left: In vivo trafficking of myeloma cells in mouse labelled with 89Zr using the tetrakis oxinate (shown centre) lipophilic complex, at 30 min and 7 days after administration of cells.
In this project, which is an industrial collaboration with GE Healthcare, you will develop new multimodality (PET/SPECT, optical, MRI) probes for cell tracking in the whole body in humans and animals, including:
- new reporter genes that can be imaged optically and with radionuclides
- new direct cell labelling methods building on recent developments, using long half life positron (Zr-89, Mn-52, I-124) and gamma emitting radionuclides (In-111, Tc-99m)
- combine both approaches into an integrated, cross-validated platform for tracking cells in vivo in an animal model to demonstrate translational potential.