Recent advances in radionuclide therapy of neuroendocrine tumors

The successfull application of radioiodinated MIBG in neural crest tumors led also to consider the therapeutic potential of the agent in these neoplasms. Malignant pheochromocytomas (Pheos), paragangliomas (PGs), neuroblastomas (NBs), carcinoids (CAs) and medullary thyroid carcinomas (MTCs) were the most suitable tumors to treat. The therapeutic procedure essentially consists in: 1) thyroid blockade with Lugolʹs solution; 2) high specific activity 131I MIBG (\gr 1.1 GBq/mg) administration; 3) single doses, varying from 3.7 to 9.5 GBq, given by slow i.v. infusion in several therapeutic courses; 4) continuous monitoring, during the infusion of the patient (EKG, pulse rate and blood pressure), who is mantained isolated for a few days. MIBG treatment in malignant Pheos, CAs and PGs, showed to be effective for partial reduction of tumoral lesions (mainly in Pheos with 56 % of objective responses) and for palliation in metastatic tumors, also influencing the prognosis; in a few Pheos also succeeded in definitely eradicating the residual/recurrent tumor. Also in patients with stage IV NB who failed to respond to or relapsed after conventional chemotherapy, MIBG therapy showed an important palliative role. A significant therapeutic improvement in the outcome of stage III and IV NB patients was obtained by introducing 131I-MIBG as a first line therapy, partial or even complete responses occurring in more than 60% of the cases treated. Experiences combining chemotherapeutic agents and 131I-MIBG are also in progress with encouraging results. MIBG therapy is well tolerated; toxicity is limited to minor hematologic toxicity (mainly thrombocytopenia) and patients generally recover spontaneously. The risk of pancytopenia rises in patients with bone and/or bone marrow metastases (mainly children with NB); in these cases bone marrow harvesting is recommended. An alternative approach to 131I-MIBG therapy was settled in MTC, coming from radiolabeled monoclonal antibodies. A novel immunotargeting method, which includes a bispecific antibody and 131I as a radiolabel, allowing for higher total doses of radioactivity to be used, seems to be very promising.