In vivo chemistry for tumor pretargeted imaging in live mice

Using the inverse-electron-demand Diels Alder reaction we demonstrated non-invasive pretargeted tumor imaging in mice bearing LS174T colorectal xenografts. Anti-TAG72 mAb CC49 functionalized with trans-cyclooctene moieties was administered, followed 24 h later by 111In-labeled tetrazine. Pronounced tumor uptake of the 111In-tetrazine was demonstrated by SPECT/CT imaging of live mice up to 3 h post injection (tumor-to-muscle ratio: 13.1), while no tumor binding occurred in mice treated with unmodified CC49. The components exhibited a remarkable 52-57 % chemical reaction yield in mice. We are currently optimizing this system for cancer therapy.