Liver Sinusoidal Endothelial Cell Transplantation Ameliorated Radiation-induced Liver Deformation And Sulfur Colloid SPECT Defect In Mouse Livers Following Partial Liver Irradiation

Abstract

Purpose/Objective(s): To examine liver deformation and spatial liver function in a mouse model of radiation induced liver disease (RILD), using functional imaging with 99mTechnetium (99mTc) labeled Sulfur Colloid SPECT/CT. We further investigated whether liver sinusoidal endothelial cell (LSEC) transplantation can improve liver function and ameliorate deformation following image-guided stereotactic partial liver irradiation (HIR). Materials/Methods: DPPIV-deficient or C57Bl6 mice underwent a planning CBCT after gastrograffin gavage. Fifty Gy partial liver irradiation was delivered to the median lobe (ML) using the Small Animal Irradiator Platform (SARRP system) set at 220 kVP and 13.5 mA. Maximum bowel point dose was maintained under 20 Gy to prevent GI toxicity. SPECT/CT imaging was obtained using the Inveon Platform 20 mins after 99mTc Sulfur Colloid injection. Sulfur Colloid uptake was quantified in the irradiated and non-irradiated liver regions using planning CBCT isodose lines. For cell transplantation, DPPIV positive LSECs were isolated from C57Bl/6 mice and then injected intrasplenically to anesthetized congenic DPPIV-deficient mice 24 hours after HIR. The recipient mice were sacrificed 4 months post transplantation. Individual liver lobes were weighted separately and liver tissues were analyzed for engraftment and repopulation of transplanted cells using DPPIV histochemistry. Results: Partial liver irradiation to the ML resulted in a significant decrease in the ML weight from 35 4% of the liver weight to 25 3%, one to two months after irradiation. At 4 months, ML weight reached 16% of the whole liver. Sulfur colloid SPECT/CT imaging demonstrated decreased uptake in the irradiated liver regions by 20-25%, six weeks following HIR. One animal that received HIR, followed by mitotic stimulus with hepatocyte growth factor, showed virtually no uptake in the irradiated lobe with significant compensatory hypertrophy of the unirradiated liver one year after HIR. LSEC transplantation restored ML liver weight and by 4 months made up 37-40% of the liver weight while also restoring 99mTc sulfur colloid uptake in the irradiated lobe to baseline levels. DPPIV histochemistry confirmed near total replacement of the irradiated LSECs by the transplanted DPPIV positive cells. Conclusions: This data suggests that HIR resulted in a time-dependent decrease in the weight and functional uptake of 99mTc labeled sulfur colloid in the irradiated liver lobe. LSEC transplantation restored liver weight and improved liver function as demonstrated by 99mTc sulfur colloid SPECT/ CT imaging. Our data provide a rationale for investigating the use of 99mTc sulfur colloid SPECT/CT imaging to monitor patients at risk for developing RILD and LSEC transplantation to ameliorate against RILD. Author Disclosure: R. Kabarriti: None. H. Yaffe: None. W. Zhang: None. W.P. Koba: None. L. Liu: None. P. Asp: None. W.A. Tome: None. C. Guha: None.