Evaluation of Tc-99m-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin

We evaluated Tc-99m-labeled mercaptoacetyltriglycine (Tc-99m-MAG3)-biocytin as a hepatobiliary imaging agent in the absence and presence of bilirubin in mice. We then compared its pharmacokinetic parameters; peak liver/heart activity ratio (r(max)) and half clearance time (HCT) with those of Tc-99m- labeled diisopropyl-iminodiacetic acid (Tc-99m-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent (Tc-99m-MAG3 biocytin or T c-99m-disofenin) alone or in combination with bilirubin at two doses (7 and 14 mg/kg) dissolved in 5% human serum albumin. Images were acquired every 15 s for 30 min with a gamma camera equipped with a pinhole collimator, Dyn amic images showed rapid hepatic uptake of Tc-99m-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its h epatic uptake was not affected by bilirubin coinjection, whereas Tc-99m-dis ofenin coinjected with bilirubin showed a higher blood background than Tc-9 9m-disofenin alone. These qualitative findings were reflected in pharmacoki netic parameters, r(max) and HCT. The r(max) was obtained from plots of tim e versus liver/heart activity ratios obtained in equal-area regions of inte rest over the heart and liver. The HCT was calculated from the hepatic clea rance curve from plots of time versus liver activity. Tc-99m-MAG3-biocytin without bilirubin coinjection showed an r(max) of 8.9 +/- 1.3 and an HCT of 399 +/- 36 s. These values did not change even when 14 mg/kg of bilirubin were coinjected. By contrast, the parameters for Tc-99m-disofenin with bili rubin were significantly (p < 0.01) affected by 14 mg/kg of bilirubin coinj ection: r(max) was decreased from 7.9 +/- 2.5 to 1.4 +/- 0.2 and HCT was in creased from 292 +/- 32 s to 782 +/- 133 s. Tc-99m-MAG3-biocytin hepatobili ary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic functi on in patients with high bilirubin levels. NUCL MED BIOL 26;1: 43-49 1999. (C) 1998 Elsevier Science Inc.