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Title of Journal: J Nucl Cardiol

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Abbravation: Journal of Nuclear Cardiology

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Springer-Verlag

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DOI

10.1007/978-3-319-10497-3_4

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1532-6551

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Dual molecular imaging for targeting metalloprotei

Authors: Nezam Haider Dagmar Hartung Shinichiro Fujimoto Artiom Petrov Frank D Kolodgie Renu Virmani Satoru Ohshima Han Liu Jun Zhou Ai Fujimoto Atsuko Tahara Leo Hofstra Navneet Narula Chris Reutelingsperger Jagat Narula
Publish Date: 2009/08/07
Volume: 16, Issue: 5, Pages: 753-762
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Abstract

Atherosclerosis was produced in rabbits receiving highcholesterol diet HC who underwent dual radionuclide imaging with 99mTclabeled matrix metalloproteinase inhibitor MPI and 111Inlabeled annexin A5 AA5 using microSPECT/CT ID/g MPI and AA5 uptake was measured followed by histological characterization Unmanipulated animals were used as disease controls Correlation between MPI and AA5 uptake was undertaken and relationship confirmed in culture study of activated THP1 monocytesMPI and AA5 uptake was best visualized in HC diet animals n = 6 and reduced significantly after fluvastatin treatment n = 4 or diet withdrawal n = 3 ID/g MPI 087 ± 018 and AA5 03 ± 01 uptake was higher in HC than control n = 6 animals 014 ± 004 P  0001 0007 ± 0002 P  0001 and reduced substantially after diet or statin intervention There was a significant correlation between MPI and AA5 uptake r = 62 P  0001 both correlated with pathologically verified MMP9 activity macrophage content and TUNEL staining In vitro studies demonstrated MMP9 release in culture medium from apoptotic THP1 monocytesIn twothirds of patients presenting with acute coronary syndromes coronary thrombosis is associated with rupture of the fibrous cap of an atherosclerotic plaque1 The triggers for the rupture include prevalence of monocytemacrophage infiltration and their apoptosis as well as cytokine production including matrix metalloproteinases MMP Almost one half of the macrophages at the site of plaque rupture demonstrate evidence of apoptosis with activation of caspase12 In vitro experiments have confirmed the role of caspase1 in induction of apoptosis and the use of caspase1 inhibitor YVAD substantially reduced the apoptosis of macrophages in an experimental model of atherosclerosis3 On the other hand macrophage infiltration in the plaque is associated with MMP expression and in turn to degradation of extracellular matrix and cap rupture4In addition to acting as a trigger to cap rupture macrophage apoptosis and MMP activity contribute to plaque vulnerability Apoptosis of macrophages in necrotic core5 leads to enlargement of the core size greater the necrotic core volume more prone is the plaque to rupture6 On the other hand the increase in MMP in the necrotic core promotes expansive outward remodeling of the plaque7 and renders the plaque susceptible to rupture These two processes which are independently critical for plaque rupture are both related to macrophage infiltration and it is logical to presume that these processes are interrelated The apoptosis of cellular components in an atherosclerotic plaque is no longer considered an inert process Fasinduced apoptosis of smooth muscle cell SMC has been shown to produce cytokines such as monocytechemoattractant protein 1 MCP1 CINC/IL8 and other proinflammatory genes resulting in an extensive macrophage infiltration8 Similar to the SMCrelated release of cytokines it is possible that apoptosis of macrophages may also be associated with secretory activity


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  1. Anatomy and physiology of coronary blood flow
  2. Anatomy and physiology of coronary blood flow
  3. Fifty years of progress in radionuclide assessment of myocardial perfusion
  4. Buccal caffeine for the routine reversal of Persantine
  5. Multimodality molecular imaging in predicting ventricular arrhythmias and sudden cardiac death
  6. Mentorship at Distance: A new initiative of the Journal of Nuclear Cardiology
  7. Safety of vasodilator stress myocardial perfusion imaging in patients with elevated cardiac biomarkers
  8. ASNC Model Coverage Policy: Single photon myocardial perfusion imaging
  9. A selection of recent, original research papers
  10. Effect of Bayesian-penalized likelihood reconstruction on [13N]-NH3 rest perfusion quantification
  11. Impaired cardiac PET image quality due to delayed 82 Rubidium dose delivery to the heart
  12. Complete somatostatin-induced insulin suppression combined with heparin loading does not significantly suppress myocardial 18F-FDG uptake in patients with suspected cardiac sarcoidosis
  13. Left ventricular mechanical dyssynchrony by phase analysis as a prognostic indicator in heart failure
  14. “Same-Patient Processing” for multiple cardiac SPECT studies. 1. Improving LV segmentation accuracy
  15. Optimizing quantitative myocardial perfusion by positron emission tomography for guiding CAD management
  16. Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA
  17. Effect of aminophylline administration on the diagnostic yield of vasodilator myocardial perfusion imaging
  18. Quantitative I-123 mIBG SPECT in differentiating abnormal and normal mIBG myocardial uptake
  19. Warranty period of normal stress myocardial perfusion imaging in diabetic patients: A propensity score analysis
  20. Coronary steal: Revealing the diagnosis with quantitative cardiac PET/CT
  21. Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment
  22. Quantifying predictive accuracy in survival models
  23. Regadenoson pharmacologic rubidium-82 PET: A comparison of quantitative perfusion and function to dipyridamole
  24. Incremental diagnostic benefit of resolution recovery software in patients with equivocal myocardial perfusion single-photon emission computed tomography (SPECT)
  25. Prognostic value of myocardial metabolic imaging with BMIPP in the spectrum of coronary artery disease: A systematic review
  26. What are the necessary corrections for dynamic cardiac SPECT?
  27. What have we learned from CONFIRM? Prognostic implications from a prospective multicenter international observational cohort study of consecutive patients undergoing coronary computed tomographic angiography
  28. Advances in myocardial perfusion imaging
  29. Multicenter investigation comparing a highly efficient half-time stress-only attenuation correction approach against standard rest-stress Tc-99m SPECT imaging
  30. ASNC Announcement
  31. The additive prognostic value of perfusion and functional data assessed by quantitative gated SPECT in women
  32. New software methods to cope with reduced counting statistics: shorter SPECT acquisitions and many more possibilities
  33. Impact of time-of-flight on qualitative and quantitative analyses of myocardial perfusion PET studies using 13 N-ammonia
  34. Impact of time-of-flight on qualitative and quantitative analyses of myocardial perfusion PET studies using 13 N-ammonia
  35. Challenges of cardiac inflammation imaging with F-18 FDG positron emission tomography
  36. Acute hyperglycemia causes microvascular damage, leading to poor functional recovery and remodeling in patients with reperfused ST-segment elevation myocardial infarction

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