Evaluation of 99mTc-Mercaptoacetyltriglycine-Biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin

Abstract

We evaluated 99mTc-labeled mercaptoacetyltriglycine ( 99mTc-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 99mTc-labeled diisopropyl-iminodiacetic acid ( 99mTc-disofenin). Balb/c mice were injected intravenously with hepatobiliary agent ( 99mTc-MAG3-biocytin or 99mTc-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. Dynamic images showed rapid hepatic uptake of 99mTc-MAG3-biocytin, with rapid clearance from the blood and rapid excretion via the biliary system. Its hepatic uptake was not affected by bilirubin coinjection, whereas 99mTc-disofenin coinjected with bilirubin showed a higher blood background than 99mTc-disofenin alone. These qualitative findings were reflected in pharmacokinetic parameters, r max and HCT. The r max was obtained from plots of time versus liver/heart activity ratios obtained in equal-area regions of interest over the heart and liver. The HCT was calculated from the hepatic clearance curve from plots of time versus liver activity. 99mTc-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 99mTc-disofenin with bilirubin were significantly ( p < 0.01) affected by 14 mg/kg of bilirubin coinjection: r max was decreased from 7.9 ± 2.5 to 1.4 ± 0.2 and HCT was increased from 292 ± 32 s to 782 ± 133 s. 99mTc-MAG3-biocytin hepatobiliary scintigraphy in mice is not affected by bilirubin coinjection, and this hepatobiliary agent appears to offer promise for estimating hepatic function in patients with high bilirubin levels.