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Lab. Anim. Res. 2010: 26(1), 103-108 Scintigraphic Assessment of Renal Function Using 99m Tc-DTPA in Miniature Pigs with Unilateral Ureteral Obstruction Se Eun Kim 1, Kyung Mi Shim 2, Won Guk Lee 3, Seok Hwa Choi 4, Soo Hyun Park 1, Ho Jae Han 1 and Seong Soo Kang 1, * 1 College of Veterinary Medicine and Biotechnology Research Institute, Chonnam National University, Gwangju, Korea 2 Department of Radiology, Nambu University, Gwangju, Korea 3 Department of Nuclear Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea 4 College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea This study was performed to investigate the proper method for evaluating renal function in miniature pigs with unilateral ureteral obstruction. Experimental unilateral renal damage was induced after ligation of unilateral right ureter in 3 miniature pigs. On the 3rd post-operative day, scintigraphic images were obtained after 12 mci of 99m Tc-diethylentriamene pertaacetate (DTPA) intravenous injection. Renography showed that radiopharmaceutical uptakes in the right kidney were lower than those of left kidney uptakes as early as at 3 days after surgical operation. The static images of 99m Tc-DTPA enabled us to measure the relative renal function in miniature pigs with unilateral ureteral obstruction. In conclusion, renography using 99m Tc-DTPA was the useful diagnostic method to evaluate the renal function in miniature pigs. Key words: 99m Tc-diethylentriamene pertaacetate (DTPA), unilateral ureteral obstruction, renogram, miniature pig (Received 11 November 2009; Revised version received 9 March 2010; Accepted 18 March 2010) w mw y sƒwš w. j», xk, n d w» w x kw y d w (Feeny and Johnston, 1998). ù» sƒw»ƒ š w ƒ v w qù (excretory urogram) w ù w w. w q xkw y w e š, ƒ ƒ w ù» sƒ r š.» sƒ (Lee et al., 2006) ƒ ƒ nephron w» sƒw w t. d w j p ù *Corresponding author: Seong Soo Kang, Department of Veterinary Surgery, College of Veterinary Medicine, Chonnam National University, 300 Yongbong-Dong, Buk-gu, Gwangju, 500-757, Korea Tel: +82-62-530-2877 Fax: +82-62-530-2809 E-mail: vetkang@chonnam.ac.kr š, (inulin clearance) ƒ ù w (Lee et al., 1995). w sƒ š. w w e» sƒw» w ƒ t w w š, 99m Tc-dimercaptosuccinic acid (DMSA) s x» wš v w (Rushton et al., 1988). 99m Tc-DMSA z d d w» w (Ardela et al., 2002), d» wš rd y d e z w š (Hitzel et al., 2004). 99m Tc-diethylentriamene pertaacetate (DTPA) mw š mw d š (Taylor, 1999), w q x mw 99m Tc-DMSA 99m Tc-DTPA w ƒ mö x mw y w. w s» 103

104 Se Eun Kim et al. sƒƒ y s w» q, w ƒ w w œw. 99m Tc-DTPA w z w d q y š, d w» sƒ š w. lò x PWG Genetics Korea f SPF (35-45 kg) 3 w w. x x» y 23±2 o C, 55±10% w š w œ f w. x û w x e w (CNU IACUC-YB-R-2008-29). x 12 w, xylazine hydrochloride ( t, g ) 2.2 mg/kg tiletamine/zolazepam (Zoletil 50, Virbac Korea) 5 mg/kg w w w. z y wš lactated ringer's solution 10 ml/kg/hr w š atropine sulfate (y p v, ) 0.05 mg/kg w. z wš mw y w z j» 1 silk w. z s j» 2 w (Surgisorb, ) w w w, vw j» 1 w (Surgisorb, ) w w š v j» 2 w (Supramide, Ethicon) w w w s w. N 5D%51"3FOPHSBQIZ d 3 z w. x 4 w, w w. 30 y (hydration) w mw 300 ml lactated ringer's solution n w, propofol( s, wù ) 0.2 mg/kg/hr w w. z wš, z w 10 ml w Three way stop cock w 99m Tc-DTPA 12 mci mw w. t n Dual head e (GE Infinia Hawkeye) w z z w. phase I y 2 2 z w š z phase II y 20 30 z w. 99m Tc-DTPA wš z (Region of interest, ROI) t w, mw time-activity curve w. w z w mw 99m Tc-DTPA ƒ w. Ò fa» z 4 ü ùkùš d e ù ww d d û. š w z d ù d ƒ ƒ w ùkü (Figure 1 and 2). š w 3 v ƒ y w š, 9-10 ƒ v š mw Ÿ ù t 4» w ƒw y w (Figure 1 and 2). w w v ƒw 29-30 v ù s w t ùƒ wš v ü m y w (Figure 1 and 2). ù j» d w j»ƒ ƒw y w (Table 1, Figure 1). 5JNFBDUJWJUZDVSWF fa w d 36.30±5.14 d 63.70±5.14 š, d w t n z 3.14±0.48 š ù d t n z s

Scintigraphic assessment of renal function in miniature pigs 105 Figure. 1. Dynamic images in a miniature pig with unilateral ureteral obstruction after intravenous injection of 12 mci of 99m Tc-DTPA (Left: normal kidney, Right: kidney with unilateral ureteral obstruction). Figure. 2. Posterior dynamic images of a miniature pig with unilateral ureteral obstruction following injection of 99m Tc-DTPA. (A) perfusion phase, (B) excretion phase. Table 1. Values derived from time-activity curve of renogram in miniature pigs (Mean±SD) Parameter Normal Unilateral ureteral obstruction Kidney area (cm 2 ) 65.97±13.80 74.18±22.08 Time of peak (min) 3.14±0.48 31.75±0.460 Excretion half time (T 1/2, min) 12.31±0.250 NA Uptake percentage 63.70±5.140 36.30±5.140 NA: non-available. w t ùƒ w š n z 31.75±0.46 w» (Table 1, Figure 4). š w 12.31±0.25 ù d d ƒw (Table 1). w s w» w w y w š»

106 Se Eun Kim et al. Figure. 3. Schematic drawing of region of interest. (A) perfusion phase, (B) excretion phase (Left: normal kidney, Right: kidney with unilateral ureteral obstruction). Figure. 4. 99m Tc-DTPA time-activity curves from a miniature pig with unilateral ureteral obstruction (Left: normal kidney, Right: kidney with unilateral ureteral obstruction). (A) perfusion time-activity curve (time: seconds), (B) excretion time-activity curve (time: minutes). x q z ƒ (Nam and Lee, 2006). x ¾ e z q (Vanderpuye, 2002), w e, y d (Braun et al., 2007) w š (Lee, 2007), 99m Tc-DTPA mw š (Domingues et al., 2006) mw d w. Gates (2004) w 99m Tc-DTPA w 2-3 ü e d w z ƒƒ w w. 99m Tc-DTPA z e x t» w» x t, x» sƒw (Hyun et al., 1999). w r 99m Tc-DMSA w w w ùkù (Hitzel et al., 2002). 99m Tc-DMSA e technetium-99m DMSAƒ ùkù, üx w. w w ùkù e e ù, ¾

,», w w w ƒ t š (Park et al., 2001). w q x mw 99m Tc-DMSA 99m Tc-DTPA w ƒ mö x mw y w. x w ù j» w ù x š (Valentin et al., 1999). w w mw s» sƒ w» w 99m Tc-DTPA w d w» sƒ w š ww. x z 3 w 99m Tc-DTPA s» wƒ ùk û y w.» y s w» w. s ü, x s w s», ùkú. s»» y w w 3 v ü y s zƒ ùš s w e w. 10 y ü s, q, w e š, g ƒw š w (Okegawa, 1983). x» w» z 4 ü ùkû 3 v ƒ š 4 Ÿ t y w 9-10 ùkü w ùký y w (Lee, 1997). w d w t v ƒ ƒw 29-30 v t wš v ü. s w y w (Lee, 1997). š w w s w t m ¼ m s sƒw w w ww š šwš (Schlotmann et al., 2009). Time-activity curve t 63.70±5.14 w w d 36.30±5.14 ƒ ùk Scintigraphic assessment of renal function in miniature pigs 107 ù d». w m e (Russel, 1994; Barthez et al., 1999), w ¼ s, x ùkü š š (Brown, 2004). 3.14±0.48 w w 31.75±0.46 y w š,» y w. x 99m Tc-DTPA w w w d z» sƒw w. s eƒ w w ew, kƒ w» s» w w mw w z w. 99m Tc-DTPA w w w sƒ z w w» sƒ w š ƒ. q 21 (Code#20070401034006) w. k Ardela, D.E., Miguel Martinez, B., Gutierrez Duenas, J.M., Diez Pascual, R., Garcia Arcal, D. and Dominguez Vallejo, F.J. (2002) Comparative study of differential renal function by DMSA and MAG-3 in congenital unilateral uropathies. Cir. Pediatr. 15(3), 118-121. Barthez, P.Y., Smeak, D.D., Wisner, E.R., Duffey, M., Chew, D.J. and DiBartola, S.P. (1999) Effect of partial ureteral obstruction on results of renal scintigraphy in dogs. Am. J. Vet. Res. 60(11), 1383-1389. Braun, P., Pamies Guilabert, J. and Bou Alapont, M.J. (2007) Multislice CT arteriography in the pre-surgical evaluation of patients with ureteropelvic junction stenosis. Radiologia 49(2), 115-120. Brown, S.C.W. (2004) Nuclear medicine in the clinical diagnosis and treatment of obstructive uropathy. In: Nuclear Medicine in Clinical Diagnosis and Treatment (Murray, I.P.C. and Ell, P.J. ed.), 3th ed., pp 271-293, Churchill Livingstone, Edinburgh. Dominguess F.C., Fujikawa, G.Y., Decker, H., Alonso, G., Pereira, J.C. and Duarte, P.S. (2006) Comparison of relative renal function measured with either 99mTc-DTPA or 99mTc-EC dynamic scintigraphies with that measured with 99mTc- DMSA static scintigraphy. Int. Braz. J. Urol. 32(4), 405-409. Feeny, D.A. and Johnston, G.R. (1998) The kidney and ureters. In: Textbook of Veterinary Diagnostic Radiology (Thrall, D.E. ed.), 2nd ed., pp.466-478, WB Saunders, Philadelphia. Gates, G.F. (2004) Filtration fraction and its implications for

108 Se Eun Kim et al. radionuclide renography using diethylenetriaminepentaacetic acid and mercaptoacetyltriglycine. Clin. Nucl. Med. 29(4), 231-237. Hitzel, A., Liard, A., Véra, P., Manrique, A., Ménard, J.F. and Dacher, J.N. (2002) Color and power doppler sonography versus DMSA scintigraphy in acute pyelonephritis and in prediction of renal scarring. J. Nucl. Med. 43(1), 27-32. Hitzel, A., Liard, A., Dacher, J.N., Gardin, I., Ménard, J.F., Manrique, A. and Véra, P. (2004) Quantitative analysis of 99mTc-DMSA during acute pyelonephritis for prediction of long-term renal scarring. J. Nucl. Med. 45(2), 285-289. Hyun, I.Y., Choe, W.S., Kim, M.J. and Cho, K.D. (1999) TC-99m DTPA estimation of renal function from perfusion images Tc- 99m DTPA renal scan. J. Korea Soc. Transplant 18(6), 913-921. Lee, D.S. (1997) Kidney and urinary system. In: Nuclear medicine (Koh, C.S. ed.), 2nd ed., pp.513-522, Korea Medical Book Publisher, Seoul. Lee, J.B. (2007) Treatment of renal injury: practical approach. Korean J. Urol. 48(9), 885-896. Lee, J.K., Chun, H.K., Kim, S.J., Lee, S.H., Yang, C.W., Kim, Y.S., Choi, E.J., Chang, Y.S., Bang, B.K., Yang, W.J. and Chung, S.K. (1995) Clinical usefulness of GFR measured by 125Iiothalamte. J. Kor. Med. 49(5), 693-699. Lee, S.-R., Yoon, S.N., Lee, B.M., Oh, C.-K., Kim, S.J., Kim, H.S. and Shin, G.T. (2006) Changes of glomerular filtration rate of donated and remnant kidneys in a week after living donor kidney transplantation. J. Korea Soc. Transplant 20(1): 55-62. Nam, J.K. and Lee S.D. (2006) Comparison of the effectiveness of the renogram, the serial renal scan and the diuretic half time according to the renal function for interpreting a diuretic DTPA scan following pyeloplasty. Korean J. Urol. 47(4), 402-406. Okegawa, T., Jonas, P.E., DeSchryver, K., Kawasak, A. and Needleman, P. (1983) Metabolic and cellular alterations underlying the exaggerated renal prostaglandin and thromboxane synthesis in ureter obstruction in rabbits. Inflammatory response involving fibroblasts and mononuclear cells. J. Clin. Invest 71(1), 81-90. Park, K.H., Lee, K.Y., Lee, H.S., Kim, S.Y., Han, J.W., Lee, I.J., Hwang, K.T. and Kwang, S.W. (2001) The usefulness of 99mTc-DMSA scan in acute pyelonephritis and vesicoureteral reflux in children. J. Korean Nephrol. 20(2), 263-269. Rushton, H.G., Majd, M., Chandra, R. and Yim, D. (1988) Evaluation of 99m technetium-dimercapto-succinic acid renal scans in experimental acute pyelonephritis in piglets. J. Urol. 140(5), 1169-1174. Russell, C.D. (1994) Measurement and interpretation of renal transit times. In Nuclear Medicine in Clinical Diagnosis and Treatment (Murray, I.P.C. and Ell, P.J. eds.), pp 241-245, Churchill Livingstone, Edinburgh. Schlotmann, A., Clorius, J.H. and Clorius, S.N. (2009) Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery. Eur. J. Nucl. Med. Mol. Imaging 36(10), 1665-1673. Taylor, A. (1999) Radionuclide renography: a personal approach. Semin. Nucl. Med. 29, 102-127. Valentin, J.F., Lebranchu, Y. and Nivet, H. (1999) Can man live with a pig kidney? Nephrologie 20(4), 189-192. Vanderpuye, V. (2002) Renal sonography in the diagnosis of renal obstruction or hydronephrosis in patients with cervical cancer. J. Clin. Ultrasound 30(7), 424-427.