Molecular pathway-specific 99mTc-N-(3-bromo-2,4, 6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation

Brigid Joseph, Kuldeep K. Bhargava, Gene G. Tronco, Christopher J. Palestro, Sanjeev Gupta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives Inflammatory responses after cell transplantation impair engraftment of transplanted cells. We studied whether perturbations in specific molecular pathways after inflammation in a syngeneic cell transplantation model could be identified by noninvasive imaging. Methods After transplanting hepatocytes into the liver of dipeptidyl peptidase IV-deficient Fischer 344 rats, we imaged hepatobiliary excretion of 99mTc-N-(3-bromo-2,4,6- trimethyacetanilide)iminodiacetic acid ( 99mTc-mebrofenin). Fractional retention of peak hepatic mebrofenin activity over 60-min periods was correlated with parameters of hepatic inflammation. Results In healthy animals, 28 ± 6% 99mTc-mebrofenin activity was in the liver after 60 min, whereas cell transplantation dose-dependently inhibited excretion of 99mTc-mebrofenin, P value of less than 0.001. Resolution of this abnormality in 99mTc-mebrofenin transport required 2 weeks in the setting of prolonged activation of Kupffer cells with increased TNF-α and IL-6 expression. Hepatic transport of 99mTc-mebrofenin was promptly restored by anti-inflammatory treatments, including inhibition of cyclooxygenase activity, depletion of neutrophils, or blocking of inflammatory cytokines before cell transplantation. Moreover, these treatments improved transplanted cell engraftment Conclusion Molecular pathway-based imaging offers appropriate noninvasive means to address activation of innate immune responses. This will help in developing suitable strategies for characterizing and overcoming immune responses for cell and gene therapy.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalNuclear Medicine Communications
Volume30
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Cell Transplantation
Innate Immunity
Liver
Isogeneic Transplantation
Inflammation
Dipeptidyl Peptidase 4
Kupffer Cells
Inbred F344 Rats
Prostaglandin-Endoperoxide Synthases
Cell- and Tissue-Based Therapy
Genetic Therapy
Hepatocytes
Interleukin-6
Neutrophils
Anti-Inflammatory Agents
technetium Tc 99m mebrofenin
iminodiacetic acid
Cytokines
Therapeutics

Keywords

  • Cell transplantation
  • Cytokine
  • Inflammation
  • Liver
  • Mebrofenin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Molecular pathway-specific 99mTc-N-(3-bromo-2,4, 6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation. / Joseph, Brigid; Bhargava, Kuldeep K.; Tronco, Gene G.; Palestro, Christopher J.; Gupta, Sanjeev.

In: Nuclear Medicine Communications, Vol. 30, No. 2, 02.2009, p. 126-133.

Research output: Contribution to journalArticle

@article{e2eae8d6ae4240b9ab118a084453b138,
title = "Molecular pathway-specific 99mTc-N-(3-bromo-2,4, 6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation",
abstract = "Objectives Inflammatory responses after cell transplantation impair engraftment of transplanted cells. We studied whether perturbations in specific molecular pathways after inflammation in a syngeneic cell transplantation model could be identified by noninvasive imaging. Methods After transplanting hepatocytes into the liver of dipeptidyl peptidase IV-deficient Fischer 344 rats, we imaged hepatobiliary excretion of 99mTc-N-(3-bromo-2,4,6- trimethyacetanilide)iminodiacetic acid ( 99mTc-mebrofenin). Fractional retention of peak hepatic mebrofenin activity over 60-min periods was correlated with parameters of hepatic inflammation. Results In healthy animals, 28 ± 6{\%} 99mTc-mebrofenin activity was in the liver after 60 min, whereas cell transplantation dose-dependently inhibited excretion of 99mTc-mebrofenin, P value of less than 0.001. Resolution of this abnormality in 99mTc-mebrofenin transport required 2 weeks in the setting of prolonged activation of Kupffer cells with increased TNF-α and IL-6 expression. Hepatic transport of 99mTc-mebrofenin was promptly restored by anti-inflammatory treatments, including inhibition of cyclooxygenase activity, depletion of neutrophils, or blocking of inflammatory cytokines before cell transplantation. Moreover, these treatments improved transplanted cell engraftment Conclusion Molecular pathway-based imaging offers appropriate noninvasive means to address activation of innate immune responses. This will help in developing suitable strategies for characterizing and overcoming immune responses for cell and gene therapy.",
keywords = "Cell transplantation, Cytokine, Inflammation, Liver, Mebrofenin",
author = "Brigid Joseph and Bhargava, {Kuldeep K.} and Tronco, {Gene G.} and Palestro, {Christopher J.} and Sanjeev Gupta",
year = "2009",
month = "2",
doi = "10.1097/MNM.0b013e32831e89cd",
language = "English (US)",
volume = "30",
pages = "126--133",
journal = "Nuclear Medicine Communications",
issn = "0143-3636",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Molecular pathway-specific 99mTc-N-(3-bromo-2,4, 6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation

AU - Joseph, Brigid

AU - Bhargava, Kuldeep K.

AU - Tronco, Gene G.

AU - Palestro, Christopher J.

AU - Gupta, Sanjeev

PY - 2009/2

Y1 - 2009/2

N2 - Objectives Inflammatory responses after cell transplantation impair engraftment of transplanted cells. We studied whether perturbations in specific molecular pathways after inflammation in a syngeneic cell transplantation model could be identified by noninvasive imaging. Methods After transplanting hepatocytes into the liver of dipeptidyl peptidase IV-deficient Fischer 344 rats, we imaged hepatobiliary excretion of 99mTc-N-(3-bromo-2,4,6- trimethyacetanilide)iminodiacetic acid ( 99mTc-mebrofenin). Fractional retention of peak hepatic mebrofenin activity over 60-min periods was correlated with parameters of hepatic inflammation. Results In healthy animals, 28 ± 6% 99mTc-mebrofenin activity was in the liver after 60 min, whereas cell transplantation dose-dependently inhibited excretion of 99mTc-mebrofenin, P value of less than 0.001. Resolution of this abnormality in 99mTc-mebrofenin transport required 2 weeks in the setting of prolonged activation of Kupffer cells with increased TNF-α and IL-6 expression. Hepatic transport of 99mTc-mebrofenin was promptly restored by anti-inflammatory treatments, including inhibition of cyclooxygenase activity, depletion of neutrophils, or blocking of inflammatory cytokines before cell transplantation. Moreover, these treatments improved transplanted cell engraftment Conclusion Molecular pathway-based imaging offers appropriate noninvasive means to address activation of innate immune responses. This will help in developing suitable strategies for characterizing and overcoming immune responses for cell and gene therapy.

AB - Objectives Inflammatory responses after cell transplantation impair engraftment of transplanted cells. We studied whether perturbations in specific molecular pathways after inflammation in a syngeneic cell transplantation model could be identified by noninvasive imaging. Methods After transplanting hepatocytes into the liver of dipeptidyl peptidase IV-deficient Fischer 344 rats, we imaged hepatobiliary excretion of 99mTc-N-(3-bromo-2,4,6- trimethyacetanilide)iminodiacetic acid ( 99mTc-mebrofenin). Fractional retention of peak hepatic mebrofenin activity over 60-min periods was correlated with parameters of hepatic inflammation. Results In healthy animals, 28 ± 6% 99mTc-mebrofenin activity was in the liver after 60 min, whereas cell transplantation dose-dependently inhibited excretion of 99mTc-mebrofenin, P value of less than 0.001. Resolution of this abnormality in 99mTc-mebrofenin transport required 2 weeks in the setting of prolonged activation of Kupffer cells with increased TNF-α and IL-6 expression. Hepatic transport of 99mTc-mebrofenin was promptly restored by anti-inflammatory treatments, including inhibition of cyclooxygenase activity, depletion of neutrophils, or blocking of inflammatory cytokines before cell transplantation. Moreover, these treatments improved transplanted cell engraftment Conclusion Molecular pathway-based imaging offers appropriate noninvasive means to address activation of innate immune responses. This will help in developing suitable strategies for characterizing and overcoming immune responses for cell and gene therapy.

KW - Cell transplantation

KW - Cytokine

KW - Inflammation

KW - Liver

KW - Mebrofenin

UR - http://www.scopus.com/inward/record.url?scp=58549084858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58549084858&partnerID=8YFLogxK

U2 - 10.1097/MNM.0b013e32831e89cd

DO - 10.1097/MNM.0b013e32831e89cd

M3 - Article

VL - 30

SP - 126

EP - 133

JO - Nuclear Medicine Communications

JF - Nuclear Medicine Communications

SN - 0143-3636

IS - 2

ER -