~(213)Bi-DOTATOC receptor targeted alpha-radionuclide therapy induces remission in neuroendocrine tumors refractory to beta-radiation - a first in human study

摘要

Introduction: Radiopeptide therapy using beta-emitter labeled somatostatin analogues such as 90γ/~(177)Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for refractory patients are rare. Here we report the first in human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pre-treated with beta emitters. Methods: 21 patients with neuroendocrine liver metastases refractory to 90Y/177Lu -DOTATOC were treated with an intra-arterial and one patient with bone marrow carcinosis with systemic infusion of 213Bi-DOTATOC. Hematologic, kidney and endocrine toxicity was assessed according to CTCAE criteria. Radiologic response was assessed with contrast enhanced MRI and 68Ga-DOTATOC-PET/CT. More than one year of follow-up is available for all patients. Results: Biodistribution of 213Bi-DOTATOC was evaluable with 440 keV gamma emission scans and demonstrated specific tumor binding. A maximum tolerable dose of 5 GBq/cycle was found. Enduring responses were observed for most treated patients. Chronic kidney toxicity was moderate. Acute hematotoxicity was even less pronounced than with the preceding beta-therapies. Conclusion: TAT can induce remission of tumors refractory to beta-radiation with favourable acute and midterm toxicity at therapeutic effective doses.