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<p>Alpha-DaRT, an interstitial treatment, uses <sup>224</sup>Ra-based diffusing alpha-emitters to treat solid tumors by creating a high-dose region up to 5&#xa0;mm around the source. However, diffusion lengths (L<sub>diff</sub>) remain uncertain across cancer types, with current estimates from subcutaneous and limited orthotopic models. This study measured the L<sub>diff</sub> 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&#xa0;T Magnetic Resonance Imaging (MRI). At ~ 5–7&#xa0;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). <i>Ex-vivo</i> liver tissue (n = 3) was also analyzed. After four days, gamma spectroscopy measured <sup>212</sup>Pb activity, and autoradiographs and histopathology assessed L<sub>diff</sub>, tissue damage, and vascularity (H&amp;E, CD-31, CC-3). L<sub>diff</sub> was 0.36–0.84&#xa0;mm in tumors, 0.30&#xa0;mm in rectal muscle, and 1.0&#xa0;mm in liver tissue. <sup>212</sup>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 <i>in-vivo</i> L<sub>diff</sub> measurements of Alpha-DaRT in an orthotopic colorectal adenocarcinoma model, highlighting L<sub>diff</sub> variability and the need for optimization based on cancer type.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Mélodie Cyr,
  • Naim Chabaytah,
  • Joud Babik,
  • Behnaz Behmand,
  • Joanna Li,
  • Meghan Papagni,
  • Elliot Wadge,
  • Mirta Dumancic,
  • Guillaume St-Jean,
  • François E. Mercier,
  • Shirin A. Enger

摘要

Alpha-DaRT, an interstitial treatment, uses 224Ra-based diffusing alpha-emitters to treat solid tumors by creating a high-dose region up to 5 mm around the source. However, diffusion lengths (Ldiff) remain uncertain across cancer types, with current estimates from subcutaneous and limited orthotopic models. This study measured the Ldiff 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 212Pb activity, and autoradiographs and histopathology assessed Ldiff, tissue damage, and vascularity (H&E, CD-31, CC-3). Ldiff was 0.36–0.84 mm in tumors, 0.30 mm in rectal muscle, and 1.0 mm in liver tissue. 212Pb 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 Ldiff measurements of Alpha-DaRT in an orthotopic colorectal adenocarcinoma model, highlighting Ldiff variability and the need for optimization based on cancer type.