title: Uptake of technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes.
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 degrees C as compared with 37 degrees C. Depletion of adenosine triphosphate by preincubation of cells in sodium azide and 2-deoxyglucose reduced initial uptake of 99mTc-Disofenin at 37 degrees C by 50% (p less than 0.05), suggesting an energy-dependent mechanism. At 37 degrees C, 99mTc-Mebrofenin and 99mTc-Disofenin had the greatest rate of uptake. 99mTc-Disofenin and 99mTc-Lidofenin uptake was inhibited by 20 microM 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 less than 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.
authors.affiliation: Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: J A
authors.initials: JA
authors.lastname: Lan
authors.forename: L R
authors.initials: LR
authors.lastname: Chervu
authors.forename: K L
authors.initials: KL
authors.lastname: Johansen
authors.forename: A W
authors.initials: AW
authors.lastname: Wolkoff
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media; D005998:Glycine; D007098:Imino Acids; D066298:In Vitro Techniques; D008099:Liver / Q000000981:diagnostic imaging*; D008297:Male; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D051381:Rats; D013667:Technetium; D019785:Technetium Tc 99m Disofenin; D019780:Technetium Tc 99m Lidofenin
chemical_list: D000814:Aniline Compounds; D003287:Contrast Media; D007098:Imino Acids; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019780:Technetium Tc 99m Lidofenin; D013667:Technetium; C034837:technetium Tc 99m mebrofenin; D019785:Technetium Tc 99m Disofenin; D005998:Glycine