Medical device for the chelation of radionuclides (Uranium, Plutonium Thorium, Americium, Cobalt, Caesium and Strontium) following skin contamination.

Cevidra^® Calixarene was developed by the Laboratoire de RadioChimie (LRC) at the IRSN (French Institute for Radiation Protection and Nuclear Safety). More specifically, it was produced by the Internal Dosimetry Department (SDI) within the Human Radiation Protection Division (DRPH) thanks to funding from the French Defence Procurement Agency (DGA), and has been patented in France (patent FR0858703) as well as in all countries with a civilian or military nuclear programme.

Why an radionuclide chelator in the form of a cleansing cream

The cleansing cream formulation of Cevidra^® Calixarene was inspired by conversations between the teams at the IRSN and occupational physicians working for the nuclear users AREVA and EDF. The aim of these discussions was to obtain a clearer definition of the need for a pharmaceutical formulation that could provide a rapid operational response to the problem of skin contamination among people working with actinides such as Uranium.

Why choose carboxylic calix[6]arene

The molecule 1,3,5-OCH3-2,4,6-OCH2COOH-p-tertbutylcalix[6]arene (Fig. 1), also known as carboxylic calix[6]arene or just ‘calixarene’, had already been developed prior to the skin decontamination research undertaken by the LRC in order to be able to use chromatography column techniques to extract and analyse actinides (Uranium Plutonium, Americium, Cobalt, Caesium and Strontium) found in trace quantities in the urine of contaminated people and in drinking water [1,2].

Why carboxylic calix[6]arene was the best solution for treating actinide skin contamination

Calixarene had demonstrated high affinity and good chemoselectivity for actinides, and it therefore had potential for other applications, especially once the laboratory had decided upon its strategy of developing topical skin decontamination treatments using an existing chelating agent.

Having been involved with various expert enquiries into treatments for internal contamination, the Laboratoire de RadioChimie team at the IRSN identified that there was no real targeted treatment for actinide skin contamination and a lack of understanding of the effectiveness of existing treatments. In particular, there was no effective treatment for contamination from Uranium compounds, since the only existing solution was to rinse the exposed area in detergent or DTPA (diethylenetriamine pentaacetate), which did not offer targeted or effective decontamination of the radionuclide.

Project launch, ratification from the French nuclear sector and support from the Defence Procurement Agency (DGA).

The skin decontamination project did not fully begin until 2009 when it was granted joint funding from the French Defence Procurement Agency (DGA) and was the subject of a doctoral thesis.

During a meeting held by the IRSN in December 2009, the results of this thesis were presented to the EDF Coordinating Medical Officer and to doctors from the AREVA Group. The doctors from EDF and AREVA confirmed the need for such an approach, and described problems such as contaminated wounds and persistent contamination of parts of the body that are difficult to treat, for example the nails, body and head hair, scalp and skin folds.

Industrial-scale production

Laboratoire Cevidra, which owns the global licence, has since 2016 been working closely with the Laboratoire de RadioChimie at the IRSN on the design, development and industrial production of carboxylic calix[6]arene in order to market a topical formulation as a Class I medical device.