Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecules Année : 2022

Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours

Sladjana Dukic-Stefanovic
  • Fonction : Auteur
Barbara Wenzel
Valérie Roux
Thu-Hang Lai
Rodrigo Teodoro
  • Fonction : Auteur
Klaus Kopka
Elisabeth Miot-Noirault
  • Fonction : Auteur
Winnie Deuther-Conrad

Résumé

Isocitrate dehydrogenases (IDHs) are metabolic enzymes commonly mutated in human cancers (glioma, acute myeloid leukaemia, chondrosarcoma, and intrahepatic cholangiocarcinoma). These mutated variants of IDH (mIDH) acquire a neomorphic activity, namely, conversion of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate involved in tumourigenesis. Thus, mIDHs have emerged as highly promising therapeutic targets, and several mIDH specific inhibitors have been developed. However, the evaluation of mIDH status, currently performed by biopsy, is essential for patient stratification and thus treatment and follow-up. We report herein the development of new radioiodinated and radiofluorinated analogues of olutasidenib (FT-2102) as tools for noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging of mIDH1 up- and dysregulation in tumours. Nonradiolabelled derivatives 2 and 3 halogenated at position 6 of the quinolinone scaffold were synthesised and tested in vitro for their inhibitory potencies and selectivities in comparison with the lead compound FT-2102. Using a common organotin precursor, (S)-[125I]2 and (S)-[18F]3 were efficiently synthesised by radio-iododemetallation and copper-mediated radiofluorination, respectively. Both radiotracers were stable at room temperature in saline or DPBS solution and at 37 °C in mouse serum, allowing future planning of their in vitro and in vivo evaluations in glioma and chondrosarcoma models.

Domaines

Chimie

Dates et versions

hal-03868150 , version 1 (23-11-2022)

Identifiants

Citer

Valérie Weber, Lucie Arnaud, Sladjana Dukic-Stefanovic, Barbara Wenzel, Valérie Roux, et al.. Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours. Molecules, 2022, 27 (12), pp.3766. ⟨10.3390/molecules27123766⟩. ⟨hal-03868150⟩
30 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More