Theranostics for Neuroblastoma: Making Molecular Radiotherapy Work Better

Despite improvements in neuroblastoma treatment, survival figures lag behind those of many other childhood malignancies. New treatments, and better use of existing treatments, are essential to reduce mortality. Neuroblastoma expresses several molecular targets for radionuclide imaging and therapy, of which the most widely exploited is the norepinephrine transporter. [¹²³I]metaiodobenzylguanidine (MIBG) imaging and [¹³¹I]MIBG treatment, which target this physiologic pathway, have been in clinical practice for 40 y. Although therapy outcomes have been favorable, [¹³¹I]MIBG use has not yet been optimized. Somatostatin receptors and the disialoganglioside are alternative targets, but their use remains experimental. The charity Children's Cancer Research Fund organized a workshop bringing together a broad range of scientists including radiochemists, radiobiologists, radiation physicists, clinical researchers including pediatric oncologists and nuclear medicine physicians, and patient advocates from the United Kingdom, United States, and continental Europe to share their experiences with molecular imaging and radiotherapy of neuroblastoma and discuss potential ways of improving treatment outcomes and access. These include development of alternative vectors targeting somatostatin receptors and disialoganglioside, isotopes such as α-particle and Auger electron emitters with different radiation characteristics, and combinations with external-beam radiotherapy, immunotherapy, and DNA damage repair inhibitors. Barriers to progress discussed included the unpredictable radioisotope supply, production of novel radiopharmaceuticals, lack of data regarding which are the best combination therapies, and insufficient clinical facilities. The aim was to stimulate the development and assessment of more effective treatments.