Using Alpha-emitting MABG in Targeted Radiotherapy for Neuroblastoma
Neuroblastoma has been shown to be particularly susceptible to radiation therapy. However, irradiating neuroblastoma tumors is challenging, since there may be multiple tumors at any given time in many locations, which may not all have been discovered. Irradiating neuroblastoma tumors also requires exposure of a large part of the body, thereby resulting in more significant side effects.
Complexing a radioactive substance to a molecule that binds to and is taken up by neuroblastoma cells allows for injectable targeted radiotherapy, a safer, more potent way to deliver radiation to a tumor.
Targeted radiotherapy in the form of MIBG (metaiodobenzylguanidine) has played a large role in developing clinical trials and has been shown to be very effective therapy. Children with relapsed neuroblastoma often receive MIBG as part of their management and it can cause longstanding responses, but in of itself it does not typically cure the disease.
The isotope in MIBG is a “beta-emitter,” iodine-131, which breaks single strands of DNA, requiring the cell to stop dividing long enough to repair itself. Theoretically, alpha-emitting radionuclides would be more potent for targeted radiotherapy, as the alpha-emitter would cause double-stranded DNA breaks that are more difficult for a cell to repair and thus will result in more cell death. Alpha beams are also more precise, so that MABG has the potential be both more effective and less toxic than the commonly used MIBG.
John M. Maris, MD, and researchers at the Center for Childhood Cancer Research, with a grant from the Department of Defense, have developed a new alpha-emitting isotope-complexed radionuclide using astatine-211 (MABG). Laboratory studies are progressing quickly, and investigators hope to translate this research into a new therapeutic option for children with relapsed neuroblastoma.