title: ²¹³Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.
authors: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany, clemens.kratochwil@t-online.de.
authors: C
authors: C
authors: Kratochwil
authors: F L
authors: FL
authors: Giesel
authors: F
authors: F
authors: Bruchertseifer
authors: W
authors: W
authors: Mier
authors: C
authors: C
authors: Apostolidis
authors: R
authors: R
authors: Boll
authors: K
authors: K
authors: Murphy
authors: U
authors: U
authors: Haberkorn
authors: A
authors: A
authors: Morgenstern
mesh_terms: D000328:Adult; D000512:Alpha Particles / Q000009:adverse effects / Q000627:therapeutic use*; D001610:Beta Particles / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods*; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure
chemical_list: D011868:Radioisotopes; D017481:Receptors, Somatostatin; D015282:Octreotide; D001729:Bismuth; C106246:Edotreotide