Synthesis of a DOTA- C -glyco bifunctional chelating agent and preliminary in vitro and in vivo study of [ 68 Ga]Ga-DOTA- C -glyco-RGD

The design of bifunctional chelating agents (BFCA) allowing straightforward radiometal labelling of biomolecules is a current challenge. We report herein the development of a bifunctional chelating agent based on a DOTA chelator linked to a -glycosyl compound, taking advantage of the robustness and hydrophilicity of this type of carbohydrate derivative. This new BFCA was coupled with success by CuAAC with c(RGDfK) for α β integrin targeting. As attested by evaluation, the conjugate DOTA- -glyco-c(RGDfC) demonstrated high affinity for α β integrins (IC of 42 nM). [ Ga]Ga-DOTA- -glyco-c(RGDfK) was radiosynthesized straightforwardly and showed high hydrophilic property (log = -3.71) and stability (>120 min). Preliminary PET study of U87MG engrafted mice gave evidence of an interesting tumor-to-non-target area ratio. All these data indicate that [ Ga]Ga-DOTA- -glyco-c(RGDfK) allows monitoring of α β expression and could thus be used for cancer diagnosis. The DOTA- -glycoside BFCA reported here could also be used with various ligands and chelating other (radio)metals opening a broad scope of applications in imaging modalities and therapy.