Click Chemistry Enables [⁸⁹Zr]Zr-DOTA Radioimmunoconjugation for Theranostic ⁸⁹Zr-immunoPET.

ABSTRACT: There have been predictions that the use of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in zirconium-89 (⁸⁹Zr) immuno-positron emission tomography (⁸⁹Zr-immunoPET) could enhance the in vivo stability of ⁸⁹Zr radioimmunoconjugates. However, conjugating [⁸⁹Zr]Zr-DOTA to a monoclonal antibody (mAb) remains a challenge as the heat treatment required for [⁸⁹Zr]Zr-DOTA chelation can lead to thermal denaturation of the mAb moieties. We developed a method for synthesizing [⁸⁹Zr]Zr-DOTA-mAb based on a tetrazine (Tz)-conjugated bifunctional DOTA derivative 2,2',2″-(10-(1-(4-(1,2,4,5-tetrazin-3-yl)phenyl)-3,21,26-trioxo-6,9,12,15,18-pentaoxa-29-carboxy-2,22,25-triazanonacosane-29-yl)-

SUBMITTER: Imura R 

PROVIDER: S-EPMC11583970 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature