Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury

J. Gerry Kenna; John C. Waterton; Andreas Baudy; Aleksandra Galetin; Catherine D.G. Hines; Paul Hockings; Manishkumar Patel; Daniel Scotcher; Steven Sourbron; Sabina Ziemian; Gunnar Schuetz

doi:10.1007/978-1-4939-7677-5_30

Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury

J. Gerry Kenna^*, John C. Waterton, Andreas Baudy, Aleksandra Galetin, Catherine D.G. Hines, Paul Hockings, Manishkumar Patel, Daniel Scotcher, Steven Sourbron, Sabina Ziemian, Gunnar Schuetz

^*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Abstract

Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.

Original language	English
Title of host publication	Drug-Induced Liver Toxicity
Place of Publication	New York, NY
Publisher	Humana Press, Inc
Chapter	30
Pages	627-651
Number of pages	25
ISBN (Electronic)	9781493976775
ISBN (Print)	9781493976768
DOIs	https://doi.org/10.1007/978-1-4939-7677-5_30
Publication status	Published - 21 Mar 2018

Publication series

Name	Methods in Pharmacology and Toxicology
Number	9781493976768
ISSN (Print)	1557-2153
ISSN (Electronic)	1940-6053

Keywords

Bile salt export pump
Causality assessment
Drug labelling
Drug-drug interactions
Drug-induced liver injury
Gadoxetate
Hepatobiliary transporters
Hepatotoxicity

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Kenna, J. G., Waterton, J. C., Baudy, A., Galetin, A., Hines, C. D. G., Hockings, P., Patel, M., Scotcher, D., Sourbron, S., Ziemian, S., & Schuetz, G. (2018). Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury. In Drug-Induced Liver Toxicity (pp. 627-651). (Methods in Pharmacology and Toxicology; No. 9781493976768). Humana Press, Inc. https://doi.org/10.1007/978-1-4939-7677-5_30

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title = "Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury",

abstract = "Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.",

keywords = "Bile salt export pump, Causality assessment, Drug labelling, Drug-drug interactions, Drug-induced liver injury, Gadoxetate, Hepatobiliary transporters, Hepatotoxicity",

author = "Kenna, {J. Gerry} and Waterton, {John C.} and Andreas Baudy and Aleksandra Galetin and Hines, {Catherine D.G.} and Paul Hockings and Manishkumar Patel and Daniel Scotcher and Steven Sourbron and Sabina Ziemian and Gunnar Schuetz",

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doi = "10.1007/978-1-4939-7677-5_30",

language = "English",

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Kenna, JG, Waterton, JC, Baudy, A, Galetin, A, Hines, CDG, Hockings, P, Patel, M, Scotcher, D, Sourbron, S, Ziemian, S & Schuetz, G 2018, Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury. in Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology, no. 9781493976768, Humana Press, Inc, New York, NY, pp. 627-651. https://doi.org/10.1007/978-1-4939-7677-5_30

Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury. / Kenna, J. Gerry; Waterton, John C.; Baudy, Andreas et al.
Drug-Induced Liver Toxicity. New York, NY: Humana Press, Inc, 2018. p. 627-651 (Methods in Pharmacology and Toxicology; No. 9781493976768).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

TY - CHAP

T1 - Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury

AU - Kenna, J. Gerry

AU - Waterton, John C.

AU - Baudy, Andreas

AU - Galetin, Aleksandra

AU - Hines, Catherine D.G.

AU - Hockings, Paul

AU - Patel, Manishkumar

AU - Scotcher, Daniel

AU - Sourbron, Steven

AU - Ziemian, Sabina

AU - Schuetz, Gunnar

PY - 2018/3/21

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N2 - Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.

AB - Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.

KW - Bile salt export pump

KW - Causality assessment

KW - Drug labelling

KW - Drug-drug interactions

KW - Drug-induced liver injury

KW - Gadoxetate

KW - Hepatobiliary transporters

KW - Hepatotoxicity

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U2 - 10.1007/978-1-4939-7677-5_30

DO - 10.1007/978-1-4939-7677-5_30

M3 - Chapter

AN - SCOPUS:85044379859

SN - 9781493976768

T3 - Methods in Pharmacology and Toxicology

SP - 627

EP - 651

BT - Drug-Induced Liver Toxicity

PB - Humana Press, Inc

CY - New York, NY

ER -

Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury

Abstract

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Keywords

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