Diffusion of the alpha-particle emitting daughters of alpha-DaRT sources in an orthotopic murine model of colorectal adenocarcinoma

Alpha-DaRT, an interstitial treatment, uses 224 Ra-based diffusing alpha-emitters to treat solid tumors by creating a high-dose region up to 5 mm around the source. However, diffusion lengths (L diff ) remain uncertain across cancer types, with current estimates from subcutaneous and limited orthotopic models. This study measured the L diff in an orthotopic colorectal adenocarcinoma mouse model. HT-29 colorectal adenocarcinoma cells were injected into the rectal submucosa of 38 Nod scid gamma mice. Tumor growth was monitored with 7 T Magnetic Resonance Imaging (MRI). At ~ 5–7 mm, groups included active (n = 20), inert (n = 9), and control (n = 9). Active mice had Alpha-DaRT sources implanted in tumors (n = 15) and rectal muscle (n = 5). Ex-vivo liver tissue (n = 3) was also analyzed. After four days, gamma spectroscopy measured 212 Pb activity, and autoradiographs and histopathology assessed L diff , tissue damage, and vascularity (H&E, CD-31, CC-3). L diff was 0.36–0.84 mm in tumors, 0.30 mm in rectal muscle, and 1.0 mm in liver tissue. 212 Pb showed a 50–93% escape probability, with kidneys having the highest activity. Active tumors exhibited more necrosis (p = 0.034) and reduced vascularity. This study provides the first in-vivo L diff measurements of Alpha-DaRT in an orthotopic colorectal adenocarcinoma model, highlighting L diff variability and the need for optimization based on cancer type.