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Scintigraphicaspect of Rotor's Disease with Technetium-99M-.Mebrofemn

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Scintigraphicaspect of Rotor's Disease with Technetium-99M-.Mebrofemn ScintigraphicAspect of Rotor's Disease with Technetium-99m-.Mebrofemn Gilles LeBouthillier, Jacques Morais, Michel Picard, Daniel Picard, Raymonde Chartrand, and Gilles Pomier Divisions ofNuclear Medicine and Hepatology, HôpitalSaint-Luc, Universitéde Montréal,Montreal, Canada Figure 1shows a slow liver uptake with persistent visualization A28-yr-oldmale with Rotor's disease was studied with @“Tcof the cardiac blood pool and prominent kidney excretion up to mebrofenin. The scintigraphic pattern was that of a slow liver 6 hr postinjection,at whichtime intestinalactivityis seen. uptakewith unimpairedexcretionandpersistentvisualization Gallbladder activity is first present at 55 mm and gradually of the cardiac blood pool, kidneys and urinary tract up to 6 increasesthereafter. hr. The gallbladder was visualized at 55 mm postinjection. J NucIMed 1992;33:1550—1551 DISCUSSION Galli and colleagues (1) found that scintigraphic studies differed markedly in Rotor's disease, depending on which IDA-derivative is being used. They showed that with die otor's disease is an inherited hyperbilirubinemia thyl-IDA, liver uptake was absent at 60 mm with only the characterized by the abnormal uptake and storage of bili kidneys and the urinary tract being visualized. Conversely, rubin, resulting in an increased total serum bilirubin when parabutyl-IDA was injected, a faint activity was mostly ofthe conjugated form. The use ofradioactive dyes observed in the liver with unimpaired excretion, but the such as ‘311-Rosebengal and ‘31I-BSPas well as IDA kidneys and urinary tract were not seen. derivatives studies have helped understand the pathophys In clinical studies (4), @mTc@mebrofeninshowed lower iology of this disease (1—3). renal excretion and no significant difference in hepatic We present a case of Rotor's disease studied with the extraction efficiency, time of maximum hepatic radioac hepatobiliary agent mebrofenin. tivity and hepatic parenchymal washout compared to @ thus increasing its availability for CASE REPORT hepatic extraction. A 28-yr-old immigrant male originally from Sri Lanka was Our case of Rotor's disease has been studied with 99mTc@ admitted to our hospital in order to investigate a longstanding mebrofenin, which showed a slow liver uptake and an (14yr)jaundice.Onadmission,hewasasymptomaticexceptfor unimpaired excretion with the kidneys and urinary tract dark urine and occasional pale stools. His father and his brother being visualized throughout the 6-hr imaging interval. also had longstanding jaundice. Physical examination was unre markable except for obvious icteric conjunctivae. On investigation,CBCwasnormal as wereprothrombintime, serum electrolytes,urea, creatinine,ferritin, a-fetoprotein,crea A tine kinase, alkaline phosphatase, AST, ALT, amylase, cerulo plasmin, protein electrophoresis and ct1-antitrypsin. Blood glu cosewasslightlyelevated.Total bilirubinwas 173 @mole/l(3.4— 17.1 @molefliter), ofwhich conjugated bilirubin contributed 120 @mole/liter.Immunologic testing for A, B and C hepatitis proved negative. Abdominal ultrasound was normal as was the liver biopsy, although the specimen was not subjected to electronic microscopy study. The BSP test did not show any late increment D E F as seen in Dubin-Johnson's disease. A hepatobiliary scan was performed using @mTc@mebrofenin. A dose of 3 mCi was injected. Scintiphotos were obtained im mediately following injection and at 5-mm intervals for a total of 60 mm and then at 3, 5 and 6 hr. FIGURE 1. Technetium-99m-mebrofeninhepatobiliaryscintig Received Jan. 21, 1992; revision accepted Feb. 26, 1992. raphy(A)immediate,(B)25 mm,(C)55 mm,(D)3 hr, (E)6 hr and For reprints contact: Doctor Jacques Morals, Nuclear Medicine Service, (F)6 hr with leadshieldingof the upperabdomenin orderto HôpitaISaint-Luc, 1058 St-Denis, Montréal,Quebec, Canada, H2X 3J4. demonstratethe presenceof intestinalactivity. 1550 The Journal of Nuclear Medicine•Vol.33 •No. 8 •August 1992 REFERENCES dice (author's transl) (Ocr). Nuk/earmedizin 1981;20:294—298. 3. ho M, Yamada H, Kameda H, et al. Diagnosis and differentiation of constitutional hyperbilirubinemias using sequential scanning with “I-@P 1. GaIli G. Focacci C, Maini CL, ci al. The hepatic excretion of “I-Rose (mono-iodide). J Nuc/Med 197l;l2:95—97. bengal and @‘mTc-IDAderivatives in Rotor's syndrome. Eur J Nuc/ Med 4. KlingensmithWC,FritzbergAR,SpitzerVM,KuniCC,WilliamsonMR, 1982:7:31 1—317. Gerhold JP. Work in progress: clinical evaluation of Tc-99m.trimethyl. 2. TapalagaD, SzantaiJ,CotulS.TamasS.DumitrascuD. Contributionof bromo-IDA and Tc-99m.diisopropyl-IDA for hepatobiliary imaging. Ra sequential scintigraphy with “1-@Pto the differential diagnosis of jaun dio/ogy 1983;146:181—184. EDITORIAL HepaticClearanceof Technetium-99m-lminodiaceticAcid De rivatives in Hyperbilirubinemic States T he development of 99mTcHIDA ease. Thus, plasma bilirubin per se for instance y and z proteins and (N(2,6-dimethylphenyl-carba had no significant effect on the he movement across the plasma mem moylmethyl) iminodiacetic acid) by patic clearance of Tc-IDA in vivo. brane is bidirectional. Subsequently, Loberg and coworkers in 1975 (1) This finding, seemingly at odds with bilirubin undergoes conjugation and started a new era in hepatobiliary im earlier thinking, was not necessarily isthen secretedinto bile. Technetium aging. Since then, a number of IDA inconsistent with the original in-vitro IDA is believed to follow the same derivatives have been developed, thus work, since a number of additional general pathway. allowing the accurate assessment of factors, discussed below, are at play in The Rotor syndrome is thought to patency and structural integrity of the the hepatic clearance of organic an be a disorder of uptake and storage of biliary tree. ions in vivo. Our report was also con organic anions (9,10). Presumably, a An initial clinical concern was the sistent with the generally held premise defect in binding proteins leads to in potential interference of hepatic Tc that, in the absence of a conjugation creased reflux of (conjugated and un IDA uptake by high plasma bilirubin abnormality, secretion into bile was conjugated) bilirubin from the hepa levels. Such concern stemmed from the rate-limiting step in the hepatic tocytes to the plasma, thereby decreas in-vitro work showing competitive in clearance of bilirubin and that the ing net hepatic uptake. The reported hibition of Tc-IDA uptake by biiru hepatic uptake mechanism was not case, showing prolonged visualization bin in isolated hepatocytes, from stud easily saturable in vivo (6). Decreased of the cardiac blood pool up to 6 hr, ies in dogs showing decreased hepatic canalicular secretion manifests bio is consistent with this concept. One clearance of Tc-IDA after infusion of chemically as an increase in plasma might argue that the scintigraphic sulfobromophthalein (BSP) and from conjugated bilirubin, and clinical ex findings in hepatocellular disease, i.e., clinical reports suggesting an inverse perience, including our own in biliary hepatitis, are similar, but hepatitis se relationship between plasma bilirubin atresia, did confirm an inverse rela vere enough to result in so intense a levels and hepatic clearance of Tc tionship between Tc-IDA clearance cardiac blood pool would undoubt IDA (2—4).The latter,however, made and conjugated bilirubin levels (7). edly impair canalicular secretion so no distinction between hyperbilirubi The report by LeBouthillier and co that the gallbladder and bowel prob nemia with and without hepatocan workers of a patient with Rotor's dis ably would not visualize, and the liver alicular disease. ease in this issue of the Journal illus function test profile would be differ In 1988, we described a patient with trates another rate-limiting factor in ent. markedly elevated plasma bilirubin bilirubin clearance, namely hepatic Much of the information about the levels (about 36 mg/dl), but normal storage (8). Some aspects of bilirubin specific step(s) of the bilirubin path hepatic uptake and excretion of Tc metabolism are worth noting for a way involved in hereditary hyperbili IDA (5). This patient had the Crigler clearer understanding of the Rotor rubinemias has been derived from Najjar syndrome, a hereditary disor syndrome and other hereditary hyper BSP kinetic studies and our under der of bilirubin conjugation, but no bilirubinemias. Circulating bilirubin standing of these disorders continues evidence of parenchymal hepatic dis istakenup by the hepatocytefollow to evolve. The Rotor syndrome was ing detachment of biirubin from al originally thought to be a variant of bumin at the sinusoidal plasma mem the Dubin-Johnson syndrome, a dis Received Apr. 24, 1992; accepted Apr. 24, 1992. brane. Such uptake is mediated by order of canalicular secretion, but is For reprkits contact: Saul D. Sarkar, MD, Dlvi carrier proteins, including one termed now considered a separate patho sion of Nuclear Medicine, Box 1210, SUNY Health Science Center, 450 Clarkson Ave., BrOOklyn.NY bilirubin translocase. Bilirubin is then physiologic entity primarily involving 11203. bound reversibly to binding proteins, hepatic storage (10). On the other HepaticClearanceof IDA•Sarkar 1551.
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