Pretargeted Nuclear Imaging and Radioimmunotherapy Based on the Inverse Electron-Demand Diels–Alder Reaction and Key Factors in the Pretargeted Synthetic Design

Figure 1

Pretargeted PET imaging comparison of A33-TCO/⁶⁴Cu-NOTA-Tz (A1-4), A33-TCO/⁶⁴Cu-NOTA-PEG₇-Tz (B1-3), and A33-TCO/⁶⁴Cu-SarAr-Tz (C1-3). Mice bearing subcutaneous SW1222 xenografts were administered A33-TCO via tail vein injection. After 24 h, the same mice were administered ⁶⁴Cu-NOTA-Tz, ⁶⁴Cu-NOTA-PEG₇-Tz, and ⁶⁴Cu-SarAr-Tz, respectively. All three ⁶⁴Cu-labeled Tz radioligands were successfully applied to pretargeted experiments and delineated the tumor clearly (solid white arrows). ⁶⁴Cu-NOTA-Tz was eliminated slowly through the gastrointestinal pathway (dashed white arrows). ⁶⁴Cu-SarAr-Tz cleared quickly and primarily through the urinary tract, and ⁶⁴Cu-NOTA-PEG₇-Tz represented an intermediate case with excretion through both the gastrointestinal and urinary tracts (dashed white arrows) [26, 27].