Targeted Alpha Therapy: a powerful way to treat cancer

Targeted Alpha Therapy relies on a simple concept: combining the ability of biological molecules to target cancer cells with the short-range cell-killing capabilities of alpha emitters.


Key TAT advantages in fighting cancer

This approach results in an increased cytotoxic potential toward cancer cells while limiting toxicity to nearby healthy cells thanks to the short range of alpha emission in tissues (a few cells). Alpha decay consists of the emission of a helium nucleus (alpha particle). This very specific mechanism of action at the cellular level is different from those used in other types of therapies, which do not allow cell resistance mechanisms or immune escape.  The high lineic energy transfer of this particle will provoke irreparable DNA double strand breaks to surrounding cells. As a result, alpha emitters are considered as the most powerful payloads to be found for drug conjugates with fewer than five particles needed to kill a cell versus hundreds of beta emitting isotopes or thousands of toxins.

Another advantage of TAT is that it does not require internalization of vectors.

Finally, alpha emitters can be combined with a wide range of targeting vectors, thereby vastly increasing the potential range of TAT applications.


Why 212Pb?

Orano Med has a unique position in the field of TAT using 212Pb. Development of TAT has long been hindered by a lack of supply of alpha emitting radioisotopes meeting three important criteria: purity meeting radiopharmaceutical standards, scalable quantities to provide visibility on long-term development plans, and economic competitiveness. Orano Med has chosen 212Pb because it has a unique and proprietary source of raw material (thorium-232) and has developed and patented a scalable process to purify 212Pb in large quantities at a reasonable cost. 212Pb also offers other advantages: its half-life of 11 hours is longer than most widely used radioisotopes for diagnostics (6 hours for 99mTc and 2 hours for 18F) and only has a single alpha emission in its decay chain, limiting unwanted off-target effects.


Our capabilities

Since its creation, Orano Med has built strong competences:

  • For the preclinical and clinical development of 212Pb therapies:
    • Two preclinical facilities dedicated to the development of 212Pb therapies in France (in partnership with Roche) and in the US;
    • Two Phase 1 clinical trials launched in the US.
  • For the production of 212Pb with two unique facilities in the world:
    • In France with the Laboratoire Maurice Tubiana (LMT) producing 212Pb for Europe or 224Ra/212Pb generators (worldwide supply);
    • In the US with the Domestic Distribution & Purification Unit (DDPU) producing 212Pb for North America.
  • For the production and design of chelating agents for nuclear medicine since the acquisition of Macrocyclics in 2011.


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