Uptake of Technetium 99m Hepatobiliary Imaging Agents by Cultured Rat Hepatocytes

Janet A. Lan, L. Rao Chervu, Kirsten L. Johansen, Allan W. Wolkoff

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Quantitation of initial uptake of the cholescintigraphy agents, 99mTc-Lidofenin, 99mTc-Disofenin, 99mTc-Mebrofenin, and 99mTc-Arclofenin, in short-term cultured rat hepatocytes revealed a marked reduction at 4°C as compared with 37°C. Depletion of adenosine triphosphate by preincubation of cells in sodium azide and 2-deoxyglucose reduced initial uptake of 99mTc-Disofenin at 37°C by 50% (p < 0.05), suggesting an energy-dependent mechanism. At 37°C, 99mTc-Mebrofenin and 99mTc-Disofenin had the greatest rate of uptake. 99mTc-Disofenin and 99mTc-Lidofenin uptake was inhibited by 20 μM sulfobromophthalein, bilirubin, taurocholate, deoxycholate, chenodeoxycholate, and cholate, suggesting a common anionic transport mechanism. Uptake of 99mTc-Disofenin was unaffected by removal of NaCI from medium, suggesting that its transport did not proceed by the primary high-affinity uptake pathways associated with sulfobromophthalein and taurocholate, which require CI-and Na+, respectively. 99mTc-Mebrofenin uptake was inhibited only modestly by taurocholate, deoxycholate, and bilirubin (p < 0.05) and 99mTc_ Arclofenin uptake was not inhibited by the organic anions studied. These results suggest that 99mTc-Mebrofenin and 99mTc-Arclofenin might be advantageous for cholescintigraphy in severely jaundiced patients. The relatively simple in vitro methodology described in this study may be useful in the design and screening of potential new agents before proceeding to animal studies or clinical trials.

Original languageEnglish (US)
Pages (from-to)1625-1631
Number of pages7
JournalGastroenterology
Volume95
Issue number6
DOIs
Publication statusPublished - Jan 1 1988

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Keywords

  • ATP
  • BSP
  • IDA
  • SFM
  • adenosine triphosphate
  • iminodiacetic acid
  • serum-free medium
  • sulfobromophthalein

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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