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

Meyoung Kon Kim, Jürgen Seidel, Nhat Le, In Sook Kim, Tae Moo Yoo, Craig Barker, Hisataka Kobayashi, Michael V. Green, Jorge A. Carrasquillo, Chang H. Paik

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Abstract

We evaluated 99mTc-labeled mercaptoacetyltriglycine (99m)Tc- 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.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalNuclear Medicine and Biology
Volume26
Issue number1
DOIs
Publication statusPublished - 1999 Jan

Keywords

  • Excretion
  • Hyperbilirubinemia
  • Pharmacokinetics
  • Uptake

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Kim, M. K., Seidel, J., Le, N., Kim, I. S., Yoo, T. M., Barker, C., Kobayashi, H., Green, M. V., Carrasquillo, J. A., & Paik, C. H. (1999). Evaluation of 99mTc-mercaptoacetyltriglycine-biocytin as a new hepatobiliary imaging agent in mice coinjected with bilirubin. Nuclear Medicine and Biology, 26(1), 43-49. https://doi.org/10.1016/S0969-8051(98)00077-8