Figure 8.

(A) Biodistribution data for in vivo pretargeting with huA33-TCO and [¹⁷⁷Lu]Lu-DOTA-PEG₇-TZ in athymic nude mice (n = 4 per cohort) bearing subcutaneous SW1222 human colorectal cancer xenografts using pretargeting intervals of 24 (purple), 48 (light blue), or 72 (orange) hours. For each pretargeting interval, the mice were sacrificed at 4, 24, 48, and 120 h after the administration of the radioligand. The data is presented as the uptake value in %ID/g ± S.D. (B) Longitudinal therapy study of five groups of mice (n = 10 each) bearing subcutaneous SW1222 tumors depicted in a graph of normalized tumor volume as a function of time and (C) the corresponding Kaplan-Meier survival curve. The control groups received either the immunoconjugate without the radioligand (blue) or the radioligand without the immunoconjugate (red). The three treatment groups received huA33-TCO (100 μg, 0.7 nmol) followed 24 h later by 18.7 (light blue), 37.0 (purple), or 55.5 (orange) MBq (0.5, 1.0, or 1.5 mCi, respectively) (~0.7 nmol in each case) of [¹⁷⁷Lu]Lu-DOTA-PEG₇-Tz. By log-rank (Mantel-Cox) test, survival was significant (p < 0.0001) for all treatment groups. Reprinted with permission from Membreno, R., Cook, B. E., Fung, K., Lewis, J. S. & Zeglis, B. M. Click-mediated pretargeted radioimmunotherapy of colorectal carcinoma. Mol Pharm 15, 1729-1734, (2018). Copyright 2018 American Chemical Society.