Fig. 1: Murine tumor models exhibit tumor growth delay and survival improvement following low absorbed dose 225Ac-NM600 + ICI. | Nature Communications

Fig. 1: Murine tumor models exhibit tumor growth delay and survival improvement following low absorbed dose 225Ac-NM600 + ICI.

From: Priming versus propagating: distinct immune effects of alpha- versus beta-particle emitting radiopharmaceuticals when combined with immune checkpoint inhibition in mice

Fig. 1: Murine tumor models exhibit tumor growth delay and survival improvement following low absorbed dose 225Ac-NM600 + ICI.The alternative text for this image may have been generated using AI.

A NM600 chemical structure. Maximum intensity projections at the indicated times post injection from B serial PET/CT images (9.25 MBq 86Y-NM600) or C serial SPECT/CT images (18.5 MBq 177Lu-NM600) for MC38 tumor-bearing mice (arrow indicates tumor). D–F Tissue dosimetry performed using Monte Carlo methods. Excised tumors activity distribution imaged with ionizing-radiation quantum imaging detector (iQID) 48 h (G, H; MC38) or 72 h (I, K; B78) post IV injection of the following RPT agents and activities: G 3.7 MBq 86Y-NM600 + 18.5 MBq 90Y-NM600, H 13.0 MBq 177Lu-NM600, I 0.74 MBq 90Y-NM600, J 1.70 MBq 177Lu-NM600, K 18.5 kBq 225Ac-NM600. K iQID scan overlaid with photomicrograph of tumor section. Right axis denotes number of events recorded. L Treatment scheme. MC38 tumor-bearing mice were randomized to IgG2b control on days -5/0/5 (IgG2b), or 0.2 Gy (0.4625 kBq), 2 Gy (4.625 kBq) 225Ac-NM600, or no RPT on day 1 ± ICI on days −3/0/3 (ICI). M–O Tumor growth and overall survival. P Treatment scheme. B78 two-tumor-bearing mice received no treatment (No Tx), 0.2 Gy (1.85 kBq), 2 Gy (18.5 kBq) 225Ac-NM600, or no RPT on day 1 ± ICI on days 4/7/10 (ICI). Q–S Tumor growth and overall survival. B, D; C, E; F; G–K; M, N; Q–S Results of one experiment. O Results of two independent experiments. Representative image/timepoint of n = 3 (B) or n = 4 (C) replicates. D N = 3 mice: 90Y-NM600; E n = 4 mice: 177Lu-NM600; n = 9 mice used for dosimetry calculation, F n = 1 data point: 225Ac-NM600. G–K Representative image/group from n = 2 mice per treatment group. M, N N = 7: all groups. O n = 17: 2 Gy 225Ac-NM600 ± ICI, ICI, IgG2b; n = 7: 0.2 Gy 225Ac-NM600 ± ICI. Q–S N = 9: 2 Gy 225Ac-NM600 + ICI; n = 10: all other treatment groups. One-way ANOVA with Tukey’s post hoc test was used to compare 90Y-NM600 and 177Lu-NM600 absorbed doses between tissues. Linear mixed models were used to compare tumor volumes over time between various treatment groups, adjusted for multiple comparisons using Tukey’s method. Log-rank test was used to compare survival. Error bars are SEM.

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