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 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.