Synthesis and evaluation of 68Ga‐HBED‐CC‐EDBE‐folate for positron‐emission tomography imaging of overexpressed folate receptors on CT26 tumor cells.

The 68Ga is a positron‐emitting radionuclide that can be combined with bifunctional chelating agents and bioactive substances for use as positron‐emission tomography (PET) diagnostic agents. The HBED‐CC is an acyclic chelating agent that is rapidly labeled with 68Ga under mild conditions. To target cancer cells, bioactive substances can be conjugated to the carboxyl terminus of HBED‐CC. Because folic acid strongly binds to folate receptors that are overexpressed on the surfaces of many types of cancer cells, it was coupled with HBED‐CC through a small polyethylene glycol‐based linker (EDBE) to generate an active, receptor‐selective targeting system. The HBED‐CC‐EDBE‐folate (HCEF) precursor was readily labeled with 68Ga in 5 minutes at room temperature (98% radiochemical yield; 99% radiochemical purity after isolation). In cellular uptake tests, higher uptakes of 68Ga‐HCEF were observed for the CT26 and KB cell lines (which express folate receptors) than for the A549 cell line (which does not). Finally, <italic>in vivo</italic> micro‐PET measurements over 2 hours of binding in BALB/c mice into which CT26 tumors had been transplanted showed the selective accumulation of 68Ga‐HCEF in the folate receptor‐expressing CT26 tumors. These results confirmed the potential of 68Ga‐HCEF as a PET diagnostic agent for tumors that express folate receptors. [ABSTRACT FROM AUTHOR]