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.