A new animal model of atrophy–hypertrophy complex and liver damage followingYttrium‐90 lobar selective internal radiation therapy in rabbits
Keywords: 
Materias Investigacion::Ciencias de la Salud::Hepatología
Atrophy–hypertrophy complex
Liver damage
Yttrium‐90 lobar selective internal radiation therapy
Issue Date: 
2022
Publisher: 
Nature Research
Project: 
info:eu-repo/grantAgreement/MINECO/Proyectos de investigación en salud (AE en Salud)/PI13/01184/ES/ Estrategias para incrementar el rescate quirúrgico en pacientes con tumores hepáticos mediante radioembolización hepática y cardiotrofina 1
ISSN: 
0028-0836
Note: 
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Citation: 
Páramo-Alfaro, M. (María); Santamaría, E. (Eva); Idoate, M.A. (Miguel Ángel); et al. "A new animal model of atrophy–hypertrophy complex and liver damage followingYttrium‐90 lobar selective internal radiation therapy in rabbits". Nature. 12, 2022, 1777
Abstract
Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with diferent activities (0.3, 0.6 and 1.2GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced signifcant toxicity. Cranial SIRT with 0.3GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3GBq groups developed moderate damage with infammation and portal fbrosis at 15 days, partially recovering at 30 days. There was no diference in the expression of hepatocyte function and diferentiation genes between 0.3GBq and control groups. Cranial SIRT with 0.3GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity.

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