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-Oxodotreotide, 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. A Phase II trial was initiated in January 2022.

Target/Mechanism: somatostatin receptors

Carrier/Ligand: Dotamtate

Radiation Type: Alpha particle (α)