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

Eur J Nucl Med Mol Imaging. 2014 Nov;41(11):2106-19. doi: 10.1007/s00259-014-2857-9. Epub 2014 Jul 29.


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

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

Results: The biodistribution of (213)Bi-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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alpha Particles / adverse effects
  • Alpha Particles / therapeutic use*
  • Beta Particles / therapeutic use*
  • Bismuth / therapeutic use*
  • Female
  • Humans
  • Male
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods*
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / diagnostic imaging
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Octreotide / pharmacology
  • Octreotide / therapeutic use
  • Positron-Emission Tomography
  • Radioisotopes / therapeutic use
  • Receptors, Somatostatin / metabolism*
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Treatment Failure


  • Radioisotopes
  • Receptors, Somatostatin
  • Octreotide
  • Bismuth
  • Edotreotide