212Pb-DOTAMTATE (212Pb-AlphaMedix™) is a somatostatin analogue labeled with Lead-212 and developed for the treatment of patients with somatostatin receptor positive neuroendocrine tumors. On November 13, 2018, 212Pb-AR-RMX received Orphan Drug status for NET from FDA. DOTAM is a specific chelating agent with a structure similar to TCMC and actually not so close to the much well known DOTA.

The profile, in terms of targeted indications, of this drug is similar to 177Lu-Lutathera, with the additional advantage that the decay products of 212Pb are alpha emitters. Therefore, it adds the alpha emission activity to the beta activity of Lutetium-177, providing these alpha-emitters are decaying in the vicinity of the tumor cells.

A first clinical trial performed with the 203Pb analogue demonstrated that the marketed 68Ga-DOTATATE would be similarly efficient to identify the patient eligible for treatment with 212Pb-AlphaMedix than the 203Pb labeled imaging agent. As a consequence, the development of the 203Pb analogue was put on hold.

The potential indications cover all neuroendocrine tumors (NET) and the development will probably target the NET patients that were non-responders to beta-emitters.

A Phase I trial has been initiated in January 2018 with the aim to assess the safety and dose limiting toxicity of the drug and to determine its pharmacokinetic properties and preliminary effectiveness.

Target/Mechanism: somatostatine receptors

Leading Emitter: alpha particle (α)