Tracking of Dendritic Cells using Fluorine-19 label by MRI in mouse model
Biomedical science prepares for another revolution with immunotherapies being widely regarded as the next pillar of medicine. The success of cell based immunotherapies, such as dendritic cell (DC) therapies will require answers to several critical questions including the safety, efficacy, biodistrubution, metabolism kinetics and persistence of the administered cells. Although there is an international effort to address all of these questions, they remain major challenges for the translation of any new cellular therapy. On the regulatory side, these questions relate not only to traditional measures of drug safety and efficacy but also to the fundamentally different and complex characteristics of cellular therapies, such as expansion and persistence following infusion and the therapeutic kinetics of the different cell based therapies. Frequently the function of cellular therapies are characterised and measured by metabolic tests and histological examinations which provides valuable information with regards to the function of transplanted cells but not the complete picture.
At The Centre for Blood Cell Therapies (CBCT) at The Peter MacCallum Cancer Centre (Peter Mac) in Melbourne, clinicians and researchers, A/Prof Simon Harrison, Dr Dominic Wall, Ms Noelene Bergen and Dr Jyoti Arora, engage in cell tracking to try and further understand the fate of cellular therapies following administration. The aim of human in vivo imaging (or tracking) of transplanted cells is to collect non invasive, real time, serial, spatial and quantitative measures of cell migration, expansion kinetics and persistence using inert intracellular labels. Although this information is not currently a regulatory requirement for the approval of new cell and tissue therapies, these techniques can provide invaluable in vivo, post infusion data.
In a collaborative effort with imaging scientists at the NIF University of Queensland Node, they share experience using a commercial fluorine 19 (19F) label to track DC by MRI in a mouse model. In their previous studies the feasibility and limitations of tracking using nuclear scintigraphy (111In oxine) and PET (18F FDG or 64Cu PTSM) were shown. In the current study they have demonstrated that labelling with 19F is feasible and can be imaged on a clinically applicable MRI platform. The images below (unpublished data) demonstrate that MRI can detect DC migration to the draining popliteal lymph node at 24 hours post administration. The results of this study form the basis of the plan to develop this technology for use in future clinical trials in cellular therapies. The CBCT group collaborates within various departments at Peter Mac and externally with UQ and various biotechnology groups. This study was supported by Prima Biomed, Siemens Australia and National Imaging Facility