131 I-MIBG Imaging and Therapy for Neuroblastoma: Infrastructure Proposal
Neuroblastoma is a highly malignant tumor of children that arises in the peripheral sympathetic nervous system, and spreads widely to bones and bone marrow. The survival of children with metastatic neuroblastoma is less than 40%, despite intensive chemotherapy, radiation and bone marrow transplant. Metaiodobenzylguanidine (MIBG) is a chemical similar in structure to noradrenaline and specifically taken up by neuroblastoma, thus providing a means to detect tumor metastases and to deliver intravenous tumor-targeted radiation by attaching a radioactive iodine molecule. 131I-MIBG has achieved responses of 40% in children with relapsed neuroblastoma, with very few side effects, but due to the special requirements of administering radioactive medicines, is used at only a few centers and is not yet approved for commercial use by the FDA. Furthermore, there is very little pre-clinical data on using MIBG in combination with the new molecularly targeted drugs to provide a platform for overcoming resistant cancer cells. The goal of this proposal is to further improve upon the success with MIBG by pre-clinical investigation of combinations with drugs targeted to tumor specific genetic pathways in neuroblastoma, and to conduct phase I and II clinical trials of these combinations. This will be accomplished by support of our highly trained team of physicians, nurses, nuclear medicine technologists, physicists, laboratory scientists, and clinical research coordinators who work together to deliver MIBG therapy to patients, develop new approaches in the laboratory, and study new techniques for quantifying response with tumor specific imaging. This team also has the mission of teaching and educating physicians, nurses and nuclear medicine groups around the country in the appropriate use and administration of MIBG, and working to allow more widespread use. The team also is active in national clinical trials, and has already implemented several multi-institutional protocols using MIBG with chemotherapy in advanced neuroblastoma, with prior support from the Alex's Lemonade Stand Foundation. With these activities, we will facilitate treatment of patients earlier in the course of the disease by promoting national operating procedures for MIBG therapy and incorporating this therapy into national protocols. The support of the Alex's Lemonade Stand Foundation, matched by funds from the UCSF Helen P. Diller Comprehensive Cancer Center, will help to further enhance the infrastructure that is responsible for advancing this vital treatment for children with neuroblastoma, resulting in improved outcome for neuroblastoma.
2016 Final Update
The support from the Alex Lemonade Foundation has been crucial to the implementation of our new national COG pilot study of MIBG after induction chemotherapy in newly diagnosed children, to exploit the specific anti-tumor activity of this radioactive compound. We have also laid the groundwork for a large randomized trial to optimize MIBG therapy combined with other targeted radiosensitizing drugs. Finally, we began a trial of a new method of detecting neuroblastoma and assessing response with a novel extremely sensitive and quantitative PET scan using iodine-124-MIBG, and with another radiopharmaceutical 68Ga-DOTATATE.