Ismail KOKSAL, Ersoy KEKİLLİ, Reyhan KÖROĞLU, Fatih BATİ, Abdurrahman KARAMAN, Alaattin POLAT

The Value of Tc-99m Mibi for Differential Diagnosis of Biliary Atresia and Hepatitis in Rats

Cholestatic diseases in neonates which characterized by deterioration of bile passage to intestine. We investigated the usability of Tc-99m MIBI as a hepatobiliary scintigraphy radiopharmaceutical for diferential diagnosis of biliary atresia and hepatitis in experimental model. A total of 20 males Wistar albino rats who had weights ranging from 200-350 g were included in this study. Rats were randomly divided into 4 groups. Control group, sham operated group, biliary atresia group and chemical hepatitis group (with carbon tetrachloride) were created, respectively. Blood flow phases, consantration and early excreation phases was performed after an intravenous injection through the internal jugular vein of 37 MBq Tc-99m MIBI using a gamma camera. Dual late static images were obtained at the same position at 15, 30, 60, 90 and 120 min after injection. In control group, radiopharmaceutical passage into the small intestine was seen between 45 and 60 min and evidently seen between 120 and 150 min as large hyperactive focus on midline or non-linear (snaky) radiopharmaceutical accumulation at the level of kidney. In biliary atresia group, radiopharmaceutical concentration was seen normal in liver but passage into the small intestine was not seen all rats. In carbon tetrachloride group, blood flow, concentration and early excretion scintigraphic images did not differ from control group and radiopharmaceutical passage into the small intestine was seen between 45 and 60 min. Although radiopharmaceuticals passage into the intestine was not shown in all rats of biliary atresia group. We suggest that Tc-99m MIBI as a radiopharmaceutical of hepatobiliary scintigraphy would be the contribution of the differential diagnosis of biliary atresia and hepatitis in humans

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1. Batres LA, Maller ES. Laboratory Assesments of Liver Function and Injury in Chidren. In: Suchy FJ, Sokol RJ, Balistreri WF, eds, Liver Disease in Children. 2nd edition. Philadelphia: Lippincott, Williams&Wilkins. 2001:155-69.

2. Kelly DA, Stanton A. Jaundice in babies: Implications for community screening for biliary atresia. BMJ. 1995;310(6988):1172-3.

3. Balistreri WF. Neonatal cholestasis. J Pediatr. 1985;106(2):171-84.

4. Suchy FJ. Neonatal cholestasis. Pediatr Rev. 2004;25(11):388-96.

5. Daniel GB, Bahr A, Dykes JA, DeNovo R, Young K, Smith GT. Hepatic extraction efficiency and excretion rate of technetiun-99m-mebrofenin in dogs. J Nucl Med. 1996;37(11):1846–9.

6. Koruk M, Ozkilic S, Savas MC, Celen Z, Kadayifci A, Ozkilic C. Evaluation of hepatic functions and biliary dynamics in patients with liver cirrhosis by quantitative scintigraphy. Hepatogastroenterology. 2003;50(54):1803-5.

7. Demirag K, Cankayali I, Eris O, Moral AR, Pehlivan M. The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning. Adv Ther. 2005;22(2):79-86.

8. Joseph B, Bhargava KK, Tronco GG, Palestro CJ, Gupta S. Systemic and local release of inflammatory cytokines regulates hepatobiliary excretion of 99mTcmebrofenin. Nucl Med Commun. 2008;29(4):336-44.

9. Surendran S, Eswaran MB, Vijayakumar M, Rao CV. In vitro and in vivo hepatoprotective activity of Cissampelos pareira against carbon-tetrachloride induced hepatic damage. Indian J Exp Biol. 2011;49(12):939-45.

10. Xu T, Wang X, Chen G, He Y, Bie P. Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation. J Surg Res. 2013;184(2):1102-8.

11. Mukherjee S, Sur A, Maiti BR. Hepatoprotective effect of Swertia chirata on rat. Indian J Exp Biol. 1997;35(4):384-8.

12. Jansen PLM, Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport. Liver Int. 2003;23(5):315–22.

13. Tanaka Y, Chen C, Maher JM, Klaassen CD. Kupffer cell-mediated downregulation of hepatic transporter expression in rat hepatic ischemia-reperfusion. Transplantation. 2006;82(2):258.

14. Kim MK, Song BJ, Seidel J, Soh Y, Jeong KS, Kim IS, Kobayashi H, Green MV, Carrasquillo JA, Paik CH. Use of 99mTc-mercaptoacetyltriglycine (MAG3)-biocytin hepatobiliary scintigraphy to study the protective effect of a synthetic enzyme inhibitor on acute hepatotoxicity in mice. Nucl Med Biol. 1998;25(6):561-8.

15. Swift B, Yue W, Brouwer KL. Evaluation of (99m) technetium-mebrofenin and (99m)technetium-sesta MIBI as specific probes for hepatic transport protein function in rat and human hepatocytes. Pharm Res. 2010;27(9):1987-98.

16. de Graaf W, Heger M, Spruijt O, Maas A, de Bruin K, Hoekstra R, Bennink RJ, van Gulik TM. Quantitative assessment of liver function after ischemia-reperfusion injury and partial hepatectomy in rats. J Surg Res. 2012;172(1):85-94.

17. Cantürk NZ, Canturk Z, Utkan NZ, Yenisey C, Ozbilim G, Yildirir C, Yalman Y. Cytoprotective effect of alphatocopherol against liver injury induced by extrahepatic biliary obstruction. East African Medical Journal. 1998;75(2):77-80.

18. Sadeghi R, Kianifar HR, Kakhki VR, Zakavi SR, Ansari K. 99mTc sesta MIBI imaging-can it be a useful substitute for hepatobiliary scintigraphy in infantile jaundice? Nuklearmedizin. 2009;48(3):100-3.

19. Gagandeep S, Rajvanshi P, Sokhi RP, Slehria S, Palestro CJ, Bhargava KK, Gupta S. Transplanted hepatocytes engraft, survive and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis. J Pathol. 2000;191(1):78–85.

20. Joseph B, Bhargava KK, Tronco GG, Kumaran V, Palestro CJ, Gupta S. Regulation of hepatobiliary transport activity and noninvasive identification of cytokinedependent liver inflammation. J Nucl Med. 2005;46(1):146-52.

21. Martinez-Hernandez A, Delgado FM, Amenta PS. The extracellular matrix in hepatic regeneration. Localization of collagen types I, III, IV, laminin, and fibronectin. Lab Invest. 1991;64(2):157–66.

22. Wang PY, Kaneko T, Tsukada H, Nakano M, Nakajima T, Sato A. Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes. Arch Toxicol. 1997;71(10):638–45.

23. Sugano M, Cho S, Imaizumi K, Wada M. Hepatotoxicity and lipid metabolism. 3. Changes in phosphatidylcholine and phosphatidylethanolamine during hepatic injury caused by carbon tetrachloride. Biochem Pharmacol. 1970;19(7):2325–33.

24. Coleman JB, Condie LW, Lamb RG. The influence of CCl4 biotransformation on the activation of rat liver phospholipase C in vitro. Toxicol Appl Pharmacol. 1988;95(2):200–7.

25. Coleman JB, Condie LW, Lamb RG. The role of CCl4 biotransformation in the activation of hepatocytes phospholipase C in vivo and in vitro. Toxicol Appl Pharmacol. 1988;95(2):208-19