Uptake of Technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes

J. A. Lan, L. R. Chervu, K. L. Johansen, Allan W. Wolkoff

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Quantitation of initial uptake of the cholescintigraphy agents, 99mTc-Lidofenin, 99mTc-Disofenin, 99mTc-Mebrofenin, and 99mTc-Arclofenin, in shortterm 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 rat 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 NaCl from medium, suggesting that its transport did not proceed by the primary high-affinity uptake pathways associated with sulfobromophthalein and taurocholate, which require Cl- 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
StatePublished - 1988

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Technetium Tc 99m Disofenin
Technetium
Hepatocytes
Taurocholic Acid
Technetium Tc 99m Lidofenin
Sulfobromophthalein
Deoxycholic Acid
Bilirubin
Cholates
Chenodeoxycholic Acid
Sodium Azide
Deoxyglucose
Jaundice
Anions
Adenosine Triphosphate
Clinical Trials
technetium Tc 99m mebrofenin

ASJC Scopus subject areas

  • Gastroenterology

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Uptake of Technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes. / Lan, J. A.; Chervu, L. R.; Johansen, K. L.; Wolkoff, Allan W.

In: Gastroenterology, Vol. 95, No. 6, 1988, p. 1625-1631.

Research output: Contribution to journalArticle

Lan, JA, Chervu, LR, Johansen, KL & Wolkoff, AW 1988, 'Uptake of Technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes', Gastroenterology, vol. 95, no. 6, pp. 1625-1631.
Lan, J. A. ; Chervu, L. R. ; Johansen, K. L. ; Wolkoff, Allan W. / Uptake of Technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes. In: Gastroenterology. 1988 ; Vol. 95, No. 6. pp. 1625-1631.
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