213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

Purpose Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as Y-90/Lu-177-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with Bi-213-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Methods Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with Y-90/Lu-177-DOTATOC were treated with an intraarterial infusion of Bi-213-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of Bi-213-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and Ga-68-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. Results The biodistribution of Bi-213-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. Conclusion TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.