Figure 12.

(A) Schematic of the in vivo pretargeting approach using the IEDDA reaction. (B) Rossin et al. developed the first pretargeting approach using the in vivo IEDDA reaction to visualize TAG72-expressing LS174T xenografts (left) via SPECT imaging. To this end, a Tz-modified ¹¹¹In-DOTA radioligand was administered 24 h after the injection of a TCO-bearing immunoconjugate of the CC49 antibody. The use of either unmodified CC49 antibody (middle) or rituximab (no affinity for TAG72, right) instead of CC49-TCO confirmed that the accumulation of ¹¹¹In in the tumor was a product of in vivo click chemistry. (C) In a study conducted by Zeglis et al., pretargeted PET imaging was performed in mice bearing A33 antigen expressing SW1222 human colorectal carcinoma xenografts. To this end, the mice were first administered a TCO-bearing immunoconjugate of the A33 antigen-targeting antibody huA33 (huA33-TCO) followed, after a 24 h interval, by a ⁶⁴Cu- and Tz-modified radioligand (⁶⁴Cu–Tz–SarAr). Panels A and C were reprinted with permission from Zeglis et al., copyright 2015 American Chemical Society. Panel B was reprinted with permission from Rossin et al., copyright 2010 John Wiley and Sons.