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-emitting radioisotopes.

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 ray emission in tissues (a few cell layers).

Key benefits of TAT in the fight against cancer

Alpha decay consists of the emission of a helium nucleus (alpha particle) together with very high linear energy transfer. This provokes irreparable DNA double strand breaks to cells in the immediate surroundings of the emission. This specific mechanism of action hinders the development of processes of resistance or immune escape in tumor cells.

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As a result, alpha emitters are considered as the most powerful payloads to be found for targeted therapies

 

As a result, alpha emitters are considered as the most powerful payloads to be found for targeted therapies with fewer than five particles needed to kill a cancer cell versus hundreds of beta emitting isotopes or thousands of chemotherapy toxins. Another advantage of TAT is that it does not require internalization of vectors to be effective.

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

Why 212Pb ?

212Pb has all the qualities required for application in vectorized internal radiotherapy:

  • Its half-life of 11 hours is suitable for use in nuclear medicine while making it possible to offer outpatient treatment and facilitating the management of waste and effluents;

  • It only has a single alpha emission in its decay chain, avoiding any risk of remote toxicity to healthy cells;

  • The process used for its production is entirely chemical. This makes it more reliable and less costly than other processes usually used for the production of radioisotopes by cyclotron or in a nuclear reactor. 

Preclinical and clinical development


Analysis in the DDPU laboratory (Domestic Distribution and Purification Unit), located in Plano, Texas (United States) © Orano Med - HERNDON JIM
Arcolab. Orano Nuclear Medecine © Orano Med - LARRAYADIEU ERIC
Orano Med has equipped itself with all the tools necessary for the preclinical and clinical development of 212Pb-conjugated molecules with:
  • A preclinical laboratory dedicated to the development of 212Pb Targeted Alpha Therapy treatments in the USA (Plano, Texas). It is fully equipped to conduct the necessary preclinical studies to develop new molecules as well as to perform activities of peptide synthesis, bioconjugation, radiolabeling and analytical testing. Its subsidiary Macrocylics shares the same premises and manufactures on site the chelatants.

  • A second preclinical laboratory in France in partnership with Roche (Razès, Haute-Vienne), to develop novel, advanced alpha radioimmunotherapy techniques.

Two clinical trials launched by Orano Med are currently in progress:

  • A phase 2 clinical trial on neuroendocrine tumors with AlphaMedixTM
  • A phase 1 clinical trial on different types of solid tumors with an anti-GRPR peptide as a targeting molecule. 
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