Fiche publication
Date publication
juillet 2025
Journal
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck
,
Dr COLLIN Bertrand
,
Pr COCHET Alexandre
Tous les auteurs :
Cheveau M, Moreau M, Grohmann A, Robert S, Cochet A, Collin B, Boschetti F, Poty S, Denat F
Lien Pubmed
Résumé
We report the synthesis and evaluation of the first 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane-3,6,10,13-tetraacetic acid (PYTA) bifunctional chelators (BFCs) for Ac coordination. Three PYTA BFCs (PYTA-triacetate, PYTA-glutaric acid, and PYTA-pyridyl-ether) were synthesized. A comparative radiolabeling study with MACROPA, DOTA, and crown derivatives was performed. Conjugation to prostate-specific membrane antigen ligands and antibodies exemplified the applicability of these BFCs. Biodistribution and long-term stability of radiocomplexes were investigated in vivo. PYTA derivatives demonstrated excellent radiochemical properties with quantitative radiolabeling under mild conditions (37 °C; low concentration) and exhibited prolonged in vitro stability. In vivo evaluation of radioimmunoconjugates confirmed the prolonged stability of PYTA conjugates, yielding results comparable to those seen with MACROPA, and revealed the instability of crown derivatives. PYTA emerges as a promising chelator for Ac, comparable to MACROPA, with the advantages of modular BFC synthesis.
Mots clés
225Ac, bifunctional chelators, radiochemistry, targeted α-therapy, α-emitter
Référence
J Nucl Med. 2025 07 10;:
