Non-Invasive Targeted Hepatic Irradiation and SPECT/CT Functional Imaging to Study Radiation-Induced Liver Damage in Small Animal Models.

Rafi Kabarriti,Chandan Guha,N Patrik Brodin,Wolfgang A Tomé,Laibin Liu,Wade R Koba,Hillary Yaffe,Patrik Asp,Mark Barahman

doi:10.3390/cancers11111796

Abstract

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers. In the setting of modern-day radiation oncology, a truly translational animal model would require the ability to deliver RT to specific parts of the liver, through non-invasive image guidance methods. To this end, we developed a targeted hepatic irradiation model on the Small Animal Radiation Research Platform (SARRP) using contrast-enhanced cone-beam computed tomography image guidance. Using this model, we showed evidence of the early development of region-specific RILD through functional single photon emission computed tomography (SPECT) imaging.

Highlights

The incidence of liver cancer is currently increasing in the United States and represents one of the most common malignancies worldwide, with deaths related to liver cancer expected to surpass those of breast, prostate, and colorectal cancer within the few decades [1]
The irradiation procedure was well tolerated by all animals and no subjects were lost to acute GI
The irradiation procedure was well tolerated by all animals and no subjects were lost to acute syndrome or died from any other causes, showing that limiting the radiation dose to the GI tract to GI syndrome or died from any other causes, showing that limiting the radiation dose to the GI tract

Summary

Introduction

The incidence of liver cancer is currently increasing in the United States and represents one of the most common malignancies worldwide, with deaths related to liver cancer expected to surpass those of breast, prostate, and colorectal cancer within the few decades [1]. Other studies have used clinical linear accelerators to deliver whole- or partial-liver RT to rats by imaging them on a computed tomography (CT) scanner and marking the extent of the liver on the skin of the animal [8,9]. An improvement, this technique still restricts the delivery of partial-liver RT to rats due to size restrictions, and to using external skin markings to guide the field setup. The recent development of dedicated robotic platforms such as the Small Animal

Methods

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Discussion

Conclusion