Original Article

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 41, Issue 11, pp 2106-2119

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • C. KratochwilAffiliated withDepartment of Nuclear Medicine, University Hospital Heidelberg Email author 
  • , F. L. GieselAffiliated withDepartment of Nuclear Medicine, University Hospital Heidelberg
  • , F. BruchertseiferAffiliated withInstitute for Transuranium Elements, European Commission
  • , W. MierAffiliated withDepartment of Nuclear Medicine, University Hospital Heidelberg
  • , C. ApostolidisAffiliated withInstitute for Transuranium Elements, European Commission
  • , R. BollAffiliated withOak Ridge National Laboratory
  • , K. MurphyAffiliated withOak Ridge National Laboratory
  • , U. HaberkornAffiliated withDepartment of Nuclear Medicine, University Hospital Heidelberg
  • , A. MorgensternAffiliated withInstitute for Transuranium Elements, European Commission

Abstract

Purpose

Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90Y/177Lu-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 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters.

Methods

Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90Y/177Lu-DOTATOC were treated with an intraarterial infusion of 213Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients.

Results

The biodistribution of 213Bi-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.

Keywords

Targeted alpha therapy (TAT) 213Bi 225Ac DOTATOC