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 beta-emitter labeled somatostatin analogues such as 90Y/177Lu-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: Seven patients with progressive advanced 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 two years of follow-up are available for seven patients. Results: Biodistribution of 213Bi-DOTATOC was evaluable with 440 keV gamma emission scans and demonstrated specific tumor binding. Enduring responses were observed for all 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.

KRATOCHWIL Clemens;  GIESEL Frederik;  BRUCHERTSEIFER Frank;  MIER Walter;  APOSTOLIDIS Christos;  BOLL Rose;  MURPHY Karen;  HABERKORN Uwe;  MORGENSTERN Alfred; 

2014-12-09

SPRINGER

JRC71816

1619-7070,   

http://link.springer.com/article/10.1007%2Fs00259-014-2857-9,    https://publications.jrc.ec.europa.eu/repository/handle/JRC71816,   

10.1007/s00259-014-2857-9,