CDCA-Derived NE3TA Conjugate for Liver-Selective 64Cu PET Imaging.

Positron emission tomography (PET) is a highly sensitive and quantitative imaging modality that has been applied for noninvasive visualization of biochemical and metabolic processes in vivo. While PET has the potential to assess hepatobiliary function and transport, liver-selective PET tracers have not been successfully translated into clinical applications. Copper-64 (64Cu) is a positron-emitting radionuclide that has been widely explored for PET imaging of bioactive molecules. We developed an effective bifunctional chelator 3p-C-NE3TA that can securely and rapidly sequester 64Cu under mild conditions. Herein, we report the synthesis and evaluation of a CDCA-derived chelator conjugate, 3p-C-NE3TA-chenodeoxycholic acid (CDCA), for potential applications in liver-selective PET imaging. The 3p-C-NE3TA-CDCA conjugate was efficiently radiolabeled with 64Cu at room temperature. The resulting 64Cu-labeled 3p-C-NE3TA-CDCA conjugate demonstrated high stability in human serum and prominent and selective hepatic uptake with favorable clearance, as evidenced by very low activity levels in blood and nontarget tissues in healthy mice at 4 h postinjection. Taken together, these results show that 64Cu-labeled 3p-C-NE3TA-CDCA exhibits excellent radiolabeling efficiency, high in vitro and in vivo stability, and marked liver-selective biodistribution.