Authors:  Marion TISSERAUD, Sylvain AUVITY, Bertrand KUHNAST, Fabien CAILLE
Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d’Imagerie Biomédicale Multimodale Paris-Saclay, 91401 Orsay, France
Background
The p53 protein is essential for the integrity of the cell, stopping cell division in order to repair DNA or by activating apoptosis of altered cells. In several cancers, the protein p53 is deactivated, allowing for the proliferation of tumor.
Aims
The molecule CP31398 has shown specificity for mutated p53 and is able to restore this protein to suppress cancer cells in vivo.1 Isotopic labelling of CP31398 with carbon-11 would allow for PET imaging of mutated p53 for early detection of aggressive cancers and treatment orientation.
Methods
For the carbon-11 labelling of CP31398, first, the synthesis of a labelling precursor with a free alcohol will be realized. Once the precursor obtained, the labelling of the free alcohol with [11C]CH3OTf will be realized to obtain the desired radiotracer [11C]CP31398.
     
Results and Conclusion
The synthesis of the labelling precursor was carried out using 2-Methyl-4 (3H) -quinazolinone by means of a multi-stage synthesis. The precursor was thus obtained with good yields (20-30%) in 5 steps. First trials of carbon-11 labelling are therefore envisaged with the labelling precursor.
References
1. Barbara A. Foster; Heather A. Coffey; Michael J. Morin; Farzan Rastinejad, Science, New Series, Vol. 286, No. 5449. (Dec. 24, 1999), pp. 2507-2510.