A "Shake and Use" Theranostic System for Combined Radio-imaging and Photodynamic Therapy
Lead Research Organisation:
UNIVERSITY COLLEGE LONDON
Department Name: Chemistry
Abstract
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Organisations
| Description | Radiolabelling of the target radiotracer candidate was established and led to extensive troubleshooting efforts both at UCL and the partner institution, KCL. The radiochemistry has been optimised, and the radiotracer was routinely prepared for characterisation in cells and animals. A total of six different cell lines were cultured (three cell lines containing the biological marker for prostate cancer (PSMA), and three control cell lines) and characterised using FACS. Binding studies to cells did not show the expected difference between radiotracer binding to disease and control, respectively. Results remained inconclusive, most likely due to competing uptake mechanisms that are inherent to the structure of the radio tracer (passive diffusion into cells caused by porphyrin and active binding by the antigen targeting moiety. In vivo experiments were subsequently carried out in tumour xenografts containing a disease and a control cell line, respectively. PET imaging with the radiotracer candidate showed fast pharmacokinetic properties of the compound, with rapid excretion as evident from high radio tracer uptake in metabolising organs within 15 mins after injection. Tumour uptake was low, and there was no difference in between disease and control cell line bearing tumours. The biodistribution profile was confirmed ex vivo using gamma counting of selected organs after radio tracer injection. Again, there was no difference between tumours expressing the target and controls. Whilst the biological characterisation of the candidate radiotracer showed that the compound is not suitable for imaging of prostate cancer, we have data to inform about structural modifications of both the targeting moiety and the therapeutic entity, the porphyrin, in the construct. Final experiments are ongoing to assess the therapeutic potential of the compound in vitro. |
| Exploitation Route | Follow-up grant application to allow refinement of chemical structure |
| Sectors | Healthcare |