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 C -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 v β 3 integrin targeting. As attested by in vitro evaluation, the conjugate DOTA- C -glyco-c(RGDfC) demonstrated high affinity for α v β 3 integrins (IC 50 of 42 nM). [ 68 Ga]Ga-DOTA- C -glyco-c(RGDfK) was radiosynthesized straightforwardly and showed high hydrophilic property (log  D 7.4 = -3.71) and in vitro stability (>120 min). Preliminary in vivo PET study of U87MG engrafted mice gave evidence of an interesting tumor-to-non-target area ratio. All these data indicate that [ 68 Ga]Ga-DOTA- C -glyco-c(RGDfK) allows monitoring of α v β 3 expression and could thus be used for cancer diagnosis. The DOTA- C -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.