Document Detail


Molecular pathway-specific 99mTc-N-(3-bromo-2,4,6-trimethyacetanilide) iminodiacetic acid liver imaging to assess innate immune responses induced by cell transplantation.
MedLine Citation:
PMID:  19077914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 ppmTc-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-alpha and IL-6 expression. Hepatic transport of 00mTc-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.
Authors:
Brigid Joseph; Kuldeep K Bhargava; Gene G Tronco; Christopher J Palestro; Sanjeev Gupta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Nuclear medicine communications     Volume:  30     ISSN:  0143-3636     ISO Abbreviation:  Nucl Med Commun     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-05     Completed Date:  2009-03-30     Revised Date:  2013-05-14    
Medline Journal Info:
Nlm Unique ID:  8201017     Medline TA:  Nucl Med Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  126-33     Citation Subset:  IM    
Affiliation:
Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Center, Jack and Pearl Resnick Campus, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Hepatocytes / immunology*,  radionuclide imaging,  transplantation*
Imino Acids / diagnostic use*,  immunology*
Immunity, Innate / immunology*
Liver / immunology*,  radionuclide imaging*,  surgery
Organotechnetium Compounds / diagnostic use*,  immunology*
Radiopharmaceuticals / diagnostic use,  immunology
Rats
Rats, Inbred F344
Signal Transduction / immunology*
Grant Support
ID/Acronym/Agency:
M01 RR12248/RR/NCRR NIH HHS; P30 CA13330/CA/NCI NIH HHS; P30 DK041296/DK/NIDDK NIH HHS; P30 DK041296-199004/DK/NIDDK NIH HHS; P30 DK41296/DK/NIDDK NIH HHS; R01 DK046952/DK/NIDDK NIH HHS; R01 DK046952-12/DK/NIDDK NIH HHS; R01 DK071111/DK/NIDDK NIH HHS; R01 DK071111-02/DK/NIDDK NIH HHS; R01 DK46952/DK/NIDDK NIH HHS; R56 DK046952/DK/NIDDK NIH HHS; R56 DK046952-15A1/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Imino Acids; 0/Organotechnetium Compounds; 0/Radiopharmaceuticals; 0/technetium Tc 99m mebrofenin
Comments/Corrections

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