ESTRO 2024 - Abstract Book

S174

Brachytherapy - GI, paediatric, miscellaneous

ESTRO 2024

This study investigated the average effective diffusion lengths (L diff ) and 212 Pb leakage probability of the radioactive daughters of 224 Ra from Alpha-DaRT sources in an in vivo orthotopic intra-rectal colorectal adenocarcinoma model.

Material/Methods:

In this orthotopic model, HT-29 colorectal adenocarcinoma cells were injected into the submucosal layer of the intestinal wall of 28 Nod scid gamma (NSG) mice. The tumors growth and localization were monitored using a 7T magnetic resonance imaging (MRI) scanner with a rapid acquisition with relaxation enhancement (RARE) sequence. Once the tumors reached 5-7 mm in diameter, they were separated into control (n=9), inert (n=9) and active (n=10) groups. The active group was divided into two, with an injection of the source into healthy rectal muscle tissue (n=4) and in the tumor (n=6). Final imaging was completed to determine the placement of the sources within the tumors. After four days of exposure, the tumors, and organs at risk (OARs) such as the kidneys, bladder, and liver were excised and measured using gamma spectroscopy. The gamma detector measured the contribution from 212 Pb. Autoradiographs were acquired from the tumors and OARs histological slides using a Typhoon 9500. The same samples were stained with Hematoxylin-Eosin (H&E), cluster of differentiation 31 (CD 31) and cleaved-caspase 3 (CC-3) for tissue damage detection, vascularity, and apoptosis, respectively. The autoradiography responses were fit with a diffusion model and the photo-stimulated luminescence (PSL) was converted into measured activities [8]. A pathologist completed measurements and contoured each groups’ necrotic areas to be compared later with the L diff measurements. The kidneys had the highest activity from the OARs, measuring between 0.255 ± 0.0025 kBq and 0.85 ± 0.0046 kBq. The preliminary results of L diff was measured to be 0.23 ± 0.09 mm for healthy rectal muscle tissue and between ~0.5-1.0 mm in the tumors. There is a range for L diff in the tumors due to the inter-variability of the tumor micro-environment between the mice and the placement of the sources. Variability in the L diff within the same tumor was observed, depending on if the measurement was taken at the center of the source or its extremity. Figure 1 presents a contoured tumor histological section overlapped with its measured response from the autoradiograph. Since 212 Pb can escape from the tissue through the blood, it can migrate beyond the tumor site, ultimately reaching the OARs. Therefore, the 212 Pb diffusion leakage probability ( 212 Pb leakage ) was calculated [8]. The 212 Pb leakage measured for tumors ranged between 54 % and 93 %. There was no relationship between tumor size and 212 Pb leakage , however, there was a linear relationship between 212 Pb leakage and the activity uptake in the kidneys. Results: