Cucurbituril–Ferrocene: Host–Guest Based Pretargeted Positron Emission Tomography in a Xenograft Model

Abstract

Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand <i>in vivo,</i> aiming to minimize the overall radiation dose. This study investigates the use of antibody based host-guest chemistry methodology for pretargeted positron emission tomography. We hypothesize that the novel pretargeting approach reported here overcomes the challenges the current pretargeting platforms have with the <i>in vivo</i> stability and modularity of the pretargeting components. A cucurbit[7]uril host molecule modified, anti-carcinoembryonic antigen antibody (M5A; CB7-M5A) and a ⁶⁸Ga-radiolabeled ferrocene guest radioligand ([⁶⁸Ga]Ga-NOTA-PEG₃-NMe₂-Fc) were studied as potential host-guest chemistry pretargeting agents for positron emission tomography in BxPC3 xenografted nude mice. The viability of the platform was studied via <i>in vivo</i> biodistribution and positron emission tomography. Tumor uptake of [⁶⁸Ga]Ga-NOTA-PEG₃-NMe₂-Fc was significantly higher in mice which received CB7-M5A prior to the radioligand injection (pretargeted) (3.3 ± 0.7%ID/g) compared to mice which only received the radioligand (nonpretargeted) (0.2 ± 0.1%ID/g).