Extended Data Fig. 8: Additional in vivo biodistribution studies with ACP3-targeted RLTs in tumour-bearing mice.
(a) Comparison of 177Lu-ProX1-(SS)-DOTAGA (11) and 177Lu-ProX1-(RR)-DOTAGA (s39) at the 24 h time point and 62.5 nmol/kg dose. (b) Comparison of 177Lu-ProX2-DOTAGA enantiomers (s40 or s41) and 177Lu-ProX3-DOTAGA enantiomers (12 or s42) at the 2 h time point and 62.5 nmol/kg dose. (c) Comparison of 177Lu-ProX1-(SS)-DOTAGA (11), 177Lu-ProX3-(S)-DOTAGA (12), and 177Lu-ProXBM-DOTAGA (10) at the 2 h time point and 62.5 nmol/kg dose. Biodistribution studies were performed with BALB/c nu/nu female (a and b) and male (c and d) mice, at a molar activity ranging from 0.05 and 0.8 MBq/nmol (~1 MBq/mouse). Data for all biodistribution studies are presented as mean of %ID g−1 ± standard error of the mean (SEM) (n = 3 mice/group). Overall, differences in tumour uptake of ~10-20% ID/g at early time points were observed when repeating in vivo biodistribution experiments using the HT1080.hACP3 cell line (see also Fig. 5). This observation could be explained by differences in vascular permeability that naturally occur when implanting tumour cells in different animal batches. (d) In vivo biodistribution studies with 68Ga-OncoACP3 (s45, 62.5 nmol/kg) at the 1 h time point. Mice in the pre-blocking group were injected with cold OncoACP3 (50 nmol/mouse, ~2.5 µmol/kg – corresponding to a 40-fold molar excess as compared to the radioactive compound) 30 min before the administration of 68Ga-OncoACP3 (s45). Individual values are represented by circles for which bars display the average group %ID g−1 values. Error bars indicate the standard error of the mean (SEM) (n = 3 mice/group for the 68Ga-OncoACP3, n = 2 mice/group for the pre-blocking and ACP3-negative SK-RC-52.wt groups).
