Two radioactive drugs, called MIBG and LUDO, bind to the surfaces of neuroblastoma cells and are able to kill them when administered as single agents. Although these cancer-seeking, radioactive drugs have resulted in prolonged remission in patients, long-term cure of aggressive disease has not been achieved. Clinicians intend to improve the treatment of neuroblastoma by giving patients both MIBG and LUDO, increasing the likelihood of lethally irradiating all-cancerous tissue in the body.
Two radiopharmaceuticals for treatment of neuroblastoma
Professor Anthony Chalmers
University of Glasgow
1 August 2017
The most effective combination schedule of administration (whether they should be given together, or one after the other) of MIBG and LUDO cannot be predicted. This must not be assessed in patients but through laboratory experimentation.
However, the use of these radioactive drugs is associated with two problems: the targets that the drugs bind to may not be present on all regions of the tumour, and the tumour may become resistant to the treatment.
The team have created model neuroblastoma tumours which consist of MIBG targets, LUDO targets or regions which are targeted by both radioactive drugs, thus replicating the clinical situation in the laboratory. These tumours will be grown both in culture and in mice. Their treatment with various combinations of MIBG and LUDO will allow evaluation of the most effective way to deliver these radioactive drugs to increase effectiveness and minimise side effects.
The findings will be immediately applied to the treatment of patients with neuroblastoma who have been selected to receive tumour-targeted, radioactive drugs. The establishment of the optimal schedule of delivery of MIBG and LUDO will minimise the capacity of tumours, which are not cured by initial radioactive drug treatment, to develop resistance to subsequently administered targeted radiotherapy, improving cure rate. The adverse effects of radiopharmaceutical MIBG and LUDO do not overlap so adverse effects are not expected to be intensified by combination treatment.
Progress to clinical evaluation will be achieved by Dr Mark Gaze in collaboration with other members of the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN – an international organization bringing together healthcare professionals from across Europe and beyond to improve treatments for children with neuroblastoma) and the Children’s Cancer and Leukaemia Group. Dr Gaze is the chief investigator on the current phase 2 clinical trial of radioactive drug treatment in children with primary refractory or relapsed high risk neuroblastoma.
The team consists of Professor Anthony Chalmers and Drs Colin Rae, Donna Nile, Mathias Tesson and Mark Gaze.
Prof Chalmers is a Radiation Oncologist whose group is dedicated to the development of strategies to improve the effectiveness of radiation treatment and has a strong track record of translating experimental therapy into novel treatments.
Dr Nile will undertake the day-to-day laboratory work required for the project, as well as the design of experiments and preparation of manuscripts for dissemination. Dr Nile is an experienced researcher and has investigated the effects of targeted radiotherapy of neuroblastoma for 6 years.
Dr Rae has been a member of the Radiation Oncology Research Group for 10 years and is an experienced investigator of mechanisms of drug action in cancer cells. Dr Tesson has been a member of the group for 10 years and provided experimental results which constituted the basis of the project. Drs Rae and Tesson will contribute to study design and interpretation of experimental data.
Dr Gaze, Consultant Oncologist, University College Hospital, London, is a long-time collaborator of the group. He has previously applied combinations of radioactive and non-radioactive drugs, developed in our laboratory, to the treatment of neuroblastoma, demonstrating his aptitude for facilitating the progress of therapeutic strategies from the laboratory to clinical practice. Close collaboration with Dr Gaze will ensure that positive findings of the proposed study will be rapidly communicated to the international clinical community, parents’ groups and the neuroblastoma charities.