- Professor Experimental Radiation Oncology (Epigenetics)
My research involves the development of targeting strategies to improve the biological specificity and effectiveness of radiation treatment by the selective delivery of radionuclides to tumour cells (targeted radiotherapy), by enhanced uptake of radiolabelled targeting agents and by the selective sensitisation of tumour cells to radiation.
By dint of close collaboration with clinician, the work has progressed beyond the simple concept of targeted radionuclide therapy to the evaluation of combined targeted chemo-radiotherapy.
Based on encouraging evidence of synergy between topotecan and [131I]MIBG from both in vitro experimental data and results of studies in murine xenograft models, the combination has been piloted in children with neuroblastoma and an international multicentre Phase II study has been developed with the International Society of Paediatric Oncology Neuroblastoma Research Network.
Other approaches to enhance this type of treatment include the use of chemotherapy, differentiating agents and gene transfer technology to improve the uptake of targeting vehicles by tumour cells and the use of alternative radionuclides. We have devised novel radiopharmaceutical manufacturing methods to produce innovative formulations of [131I]MIBG, and demonstrated that the resulting no-carrier-added [131I]MIBG has more favourable pharmacokinetics and biodistribution in vivo. As a result of this and my collaborative work with industry and clinicians, clinical trials of no-carrier-added [131I]MIBG in neuroendocrine tumours have commenced on both sides of the Atlantic Ocean.
Another major focus of targeted therapy research is the treatment of malignant melanoma and prostate carcinoma using novel, high affinity radiopharmaceuticals specific for melanin and PSMA respectively.
This work has been funded by a series of grants totalling £5,920,000 since 1999.
Group members: Ms Lesley Wilson, Ms Nazia Baig, Dr Colin Rae, M Mathias Tesson, Dr Sharon Hutchison, Mr Ujwal Dahal.