Advanced search
1 file | 453.70 KB Add to list

In vivo visualization and quantification of (disturbed) Oatp-mediated hepatic uptake and Mrp2-mediated biliary excretion of 99mTc-mebrofenin in mice

(2013) JOURNAL OF NUCLEAR MEDICINE. 54(4). p.624-630
Author
Organization
Abstract
Hepatic transport of Tc-99m-mebrofenin through organic anion transport protein 1a and 1b (Oatp1a/1b) and multidrug resistance protein 2 (Mrp2) was investigated by small-animal SPECT. On the basis of the results, a noninvasive method to visualize and quantify disturbances in hepatic transport is proposed. Methods: Friend virus B wild-type mice (untreated, bile duct-ligated, vehicle-or rifampicin-treated) and strain-matched knockout mice unable to express the uptake transporters Oatp1a/1b (Slco1a/1b(-/-)/(-/-)) or the efflux transporter Mrp2 (Abcc2(-/-)) were intravenously injected with Tc-99m-mebrofenin (n = 3 per group). After dynamic small-animal SPECT and short CT acquisitions, time-activity curves of the liver and of the gallbladder and intestines were obtained and correlated with direct blood samples. Results: Normal hepatobiliary clearance of Tc-99m-mebrofenin was severely impaired in the bile duct-ligated animal, as evidenced by elevated hepatic tracer levels. In Slco1a/1b2(-/-)/(-/-) mice, a lower area under the curve (AUC) for the liver (P = 0.014) was obtained and no activity was detected in the gallbladder and intestines. Renal rerouting was observed, along with an increase in the blood AUC (P = 0.01). Abcc2(-/-) mice had a higher liver AUC (P = 0.009), a delayed emergence time of Tc-99m-mebrofenin in the gallbladder (P = 0.009), and a lower AUC for the gallbladder and intestines (P = 0.001). The blood curve was similar to that of wild-type mice. Tc-99m-mebrofenin disposition was altered after rifampicin treatments. We observed a dose-dependent delayed time point at which tracer maximized in liver, an increased AUC for liver, and a lower AUC for gallbladder and intestines (P = 0.042, 0.034, and 0.001, respectively, highest dose). Emergence in the gallbladder occurred later (P = 0.009, highest dose), and blood AUC was higher (P = 0.006). Conclusion: The current study visualized and quantified hepatic uptake and biliary efflux of Tc-99m-mebrofenin. Our results demonstrated the possibility of discriminating, on a quantitative level, between lack of functional activity of sinusoidal uptake versus that of biliary efflux transporters.
Keywords
HEPATOBILIARY TRANSPORT, BILE-ACID TRANSPORTERS, DRUGS, RIFAMPICIN, MRP2, Tc-99m-mebrofenin, hepatobiliary transport, small-animal SPECT, Mrp2, Oatp1a/1b

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 453.70 KB

Citation

Please use this url to cite or link to this publication:

MLA
Neyt, Sara, Maarten T Huisman, Christian Vanhove, et al. “In Vivo Visualization and Quantification of (disturbed) Oatp-mediated Hepatic Uptake and Mrp2-mediated Biliary Excretion of 99mTc-mebrofenin in Mice.” JOURNAL OF NUCLEAR MEDICINE 54.4 (2013): 624–630. Print.
APA
Neyt, S., Huisman, M. T., Vanhove, C., De Man, H., Vliegen, M., Moerman, L., Dumolyn, C., et al. (2013). In vivo visualization and quantification of (disturbed) Oatp-mediated hepatic uptake and Mrp2-mediated biliary excretion of 99mTc-mebrofenin in mice. JOURNAL OF NUCLEAR MEDICINE, 54(4), 624–630.
Chicago author-date
Neyt, Sara, Maarten T Huisman, Christian Vanhove, Hilde De Man, Maarten Vliegen, Lieselotte Moerman, Caroline Dumolyn, Geert Mannens, and Filip De Vos. 2013. “In Vivo Visualization and Quantification of (disturbed) Oatp-mediated Hepatic Uptake and Mrp2-mediated Biliary Excretion of 99mTc-mebrofenin in Mice.” Journal of Nuclear Medicine 54 (4): 624–630.
Chicago author-date (all authors)
Neyt, Sara, Maarten T Huisman, Christian Vanhove, Hilde De Man, Maarten Vliegen, Lieselotte Moerman, Caroline Dumolyn, Geert Mannens, and Filip De Vos. 2013. “In Vivo Visualization and Quantification of (disturbed) Oatp-mediated Hepatic Uptake and Mrp2-mediated Biliary Excretion of 99mTc-mebrofenin in Mice.” Journal of Nuclear Medicine 54 (4): 624–630.
Vancouver
1.
Neyt S, Huisman MT, Vanhove C, De Man H, Vliegen M, Moerman L, et al. In vivo visualization and quantification of (disturbed) Oatp-mediated hepatic uptake and Mrp2-mediated biliary excretion of 99mTc-mebrofenin in mice. JOURNAL OF NUCLEAR MEDICINE. 2013;54(4):624–30.
IEEE
[1]
S. Neyt et al., “In vivo visualization and quantification of (disturbed) Oatp-mediated hepatic uptake and Mrp2-mediated biliary excretion of 99mTc-mebrofenin in mice,” JOURNAL OF NUCLEAR MEDICINE, vol. 54, no. 4, pp. 624–630, 2013.
@article{2119049,
  abstract     = {Hepatic transport of Tc-99m-mebrofenin through organic anion transport protein 1a and 1b (Oatp1a/1b) and multidrug resistance protein 2 (Mrp2) was investigated by small-animal SPECT. On the basis of the results, a noninvasive method to visualize and quantify disturbances in hepatic transport is proposed. Methods: Friend virus B wild-type mice (untreated, bile duct-ligated, vehicle-or rifampicin-treated) and strain-matched knockout mice unable to express the uptake transporters Oatp1a/1b (Slco1a/1b(-/-)/(-/-)) or the efflux transporter Mrp2 (Abcc2(-/-)) were intravenously injected with Tc-99m-mebrofenin (n = 3 per group). After dynamic small-animal SPECT and short CT acquisitions, time-activity curves of the liver and of the gallbladder and intestines were obtained and correlated with direct blood samples. Results: Normal hepatobiliary clearance of Tc-99m-mebrofenin was severely impaired in the bile duct-ligated animal, as evidenced by elevated hepatic tracer levels. In Slco1a/1b2(-/-)/(-/-) mice, a lower area under the curve (AUC) for the liver (P = 0.014) was obtained and no activity was detected in the gallbladder and intestines. Renal rerouting was observed, along with an increase in the blood AUC (P = 0.01). Abcc2(-/-) mice had a higher liver AUC (P = 0.009), a delayed emergence time of Tc-99m-mebrofenin in the gallbladder (P = 0.009), and a lower AUC for the gallbladder and intestines (P = 0.001). The blood curve was similar to that of wild-type mice. Tc-99m-mebrofenin disposition was altered after rifampicin treatments. We observed a dose-dependent delayed time point at which tracer maximized in liver, an increased AUC for liver, and a lower AUC for gallbladder and intestines (P = 0.042, 0.034, and 0.001, respectively, highest dose). Emergence in the gallbladder occurred later (P = 0.009, highest dose), and blood AUC was higher (P = 0.006). Conclusion: The current study visualized and quantified hepatic uptake and biliary efflux of Tc-99m-mebrofenin. Our results demonstrated the possibility of discriminating, on a quantitative level, between lack of functional activity of sinusoidal uptake versus that of biliary efflux transporters.},
  author       = {Neyt, Sara and Huisman, Maarten T and Vanhove, Christian and De Man, Hilde and Vliegen, Maarten and Moerman, Lieselotte and Dumolyn, Caroline and Mannens, Geert and De Vos, Filip},
  issn         = {0161-5505},
  journal      = {JOURNAL OF NUCLEAR MEDICINE},
  keywords     = {HEPATOBILIARY TRANSPORT,BILE-ACID TRANSPORTERS,DRUGS,RIFAMPICIN,MRP2,Tc-99m-mebrofenin,hepatobiliary transport,small-animal SPECT,Mrp2,Oatp1a/1b},
  language     = {eng},
  number       = {4},
  pages        = {624--630},
  title        = {In vivo visualization and quantification of (disturbed) Oatp-mediated hepatic uptake and Mrp2-mediated biliary excretion of 99mTc-mebrofenin in mice},
  url          = {http://dx.doi.org/10.2967/jnumed.112.108233},
  volume       = {54},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: