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

Alpha radiation is characterized by high linear energy transfer causing production of 2,000 – 7,000 ion pairs per micrometre, leading to clustered double-strand DNA breaks resulting in rapid cell death from even a single exposure to a few alpha particles. The short range of alpha particles (50 – 100 μm, i.e. about two or three cell diameters) limits the effective range of treatment but also limits damage to untargeted tissue.

This study retrospectively examines the safety profile of an alpha emitter in patients refractory to therapy with standard beta emitters 90Y/177Lu-DOTATOC. This is the first report the first-in-human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pre-treated with beta emitters.

Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90Y/177Lu-DOTATOC were treated with an intra-arterial infusion of 213Bi-DOTATOC, and one patient with bone marrow involvement 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: Enduring stable disease or partial responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies.

213Bi-DOTATOC can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. This is the first study presented in humans and therefore, further larger scale prospective studies are required. This is a promising development in the treatment of patients with metastatic NET.

Source: European Journal of Nuclear Medicine and Molecular Imaging