on June 21, 2004
Published online before print June 21, 2004, doi: 10.1161/01.CIR.0000134484.11052.44
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 18, 2003
From the Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.A.J., C.-H.T., J.J.W., N.-H.H., R.W.); the Cardiology Division, Department of Internal Medicine (F.A.J., G.L.R.), and Department of Internal Medicine (J.J.W.), Massachusetts General Hospital, Harvard Medical School, Boston; and the Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Mass (A.K.H., G.L.R.). * To whom correspondence should be addressed. E-mail: fjaffer{at}partners.org.
Background--Activated factor XIII (FXIIIa) mediates fibrinolytic resistance and is a hallmark of newly formed thrombi. In vivo imaging of FXIIIa activity could further elucidate the role of this molecule in thrombosis and other biological processes and aid in the clinical detection of acute thrombi. Methods and Results--An FXIIIa-sensitive near-infrared fluorescence imaging agent (A15) was engineered by conjugating a near-infrared fluorochrome to a peptide ligand derived from the amino terminus of Conclusions--A15 is a novel optical imaging agent that is specifically crosslinked to fibrin by FXIIIa, permitting detection of FXIIIa activity in experimental thrombi in vivo. This agent should permit assessment of FXIIIa activity in a broad range of biological processes and could aid in the clinical diagnosis of acute thrombi.
Revised on March 23, 2004
Accepted on March 24, 2004
Molecular Imaging of Factor XIIIa Activity in Thrombosis Using a Novel, Near-Infrared Fluorescent Contrast Agent That Covalently Links to Thrombi
Farouc A. Jaffer MD, PhD*,
2-antiplasmin. To evaluate the molecular specificity of A15 for FXIIIa, a control agent (C15) was also synthesized by modifying a single key glutamine residue in A15. Fluorescence imaging experiments with A15 demonstrated stronger thrombosis enhancement in human plasma clots in vitro (P<0.001 versus C15 clots and other controls). A15 was found to be highly specific for the active site of FXIIIa and was covalently bound to fibrin. In vivo murine experiments with A15 demonstrated significant signal enhancement in acute intravascular thrombi (P<0.05 versus C15 group). Minimal A15 enhancement was seen in older aged thrombi (>24 hours), consistent with an expected decline of FXIIIa activity over time. Imaging results were confirmed on correlative histopathology and fluorescence microscopy.
Key words: blood factors • thrombosis • fluorescence • imaging • contrast media
This article has been cited by other articles:
 |
|
 |
|
  R.-J. J.H.M. Miserus, M. V. Herias, L. Prinzen, M. B.I. Lobbes, R.-J. Van Suylen, A. Dirksen, T. M. Hackeng, J. W.M. Heemskerk, J. M.A. van Engelshoven, M. J.A.P. Daemen, et al. Molecular MRI of Early Thrombus Formation Using a Bimodal {alpha}2-Antiplasmin-Based Contrast Agent J. Am. Coll. Cardiol. Img., August 1, 2009; 2(8): 987 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nahrendorf, D. E. Sosnovik, B. A. French, F. K. Swirski, F. Bengel, M. M. Sadeghi, J. R. Lindner, J. C. Wu, D. L. Kraitchman, Z. A. Fayad, et al. Multimodality Cardiovascular Molecular Imaging, Part II Circ Cardiovasc Imaging, January 1, 2009; 2(1): 56 - 70. [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Jaffer, P. Libby, and R. Weissleder Molecular Imaging of Cardiovascular Disease Circulation, August 28, 2007; 116(9): 1052 - 1061. [Full Text] [PDF]
|
|
|
|
|
|
R. Flaumenhaft, E. Tanaka, G. J. Graham, A. M. De Grand, R. G. Laurence, K. Hoshino, R. J. Hajjar, and J. V. Frangioni Localization and Quantification of Platelet-Rich Thrombi in Large Blood Vessels With Near-Infrared Fluorescence Imaging Circulation, January 2, 2007; 115(1): 84 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Jaffer, P. Libby, and R. Weissleder Molecular and Cellular Imaging of Atherosclerosis: Emerging Applications J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1328 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nahrendorf, K. Hu, S. Frantz, F. A. Jaffer, C.-H. Tung, K.-H. Hiller, S. Voll, P. Nordbeck, D. Sosnovik, S. Gattenlohner, et al. Factor XIII Deficiency Causes Cardiac Rupture, Impairs Wound Healing, and Aggravates Cardiac Remodeling in Mice With Myocardial Infarction Circulation, March 7, 2006; 113(9): 1196 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pilch, D. M. Brown, M. Komatsu, T. A. H. Jarvinen, M. Yang, D. Peters, R. M. Hoffman, and E. Ruoslahti Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds PNAS, February 21, 2006; 103(8): 2800 - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Skotland, S. O. Hustvedt, I. Oulie, P. B. Jacobsen, G. A. Friisk, A. S. Langoy, S. Uran, J. Sandosham, A. Cuthbertson, and K. G. Toft NC100668, A NEW TRACER FOR IMAGING OF VENOUS THROMBOEMBOLISM: DISPOSITION AND METABOLISM IN RATS Drug Metab. Dispos., January 1, 2006; 34(1): 111 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J Cassidy and G. K Radda Molecular imaging perspectives J R Soc Interface, June 22, 2005; 2(3): 133 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Mazooz, T. Mehlman, T.-S. Lai, C. S. Greenberg, M. W. Dewhirst, and M. Neeman Development of Magnetic Resonance Imaging Contrast Material for In vivo Mapping of Tissue Transglutaminase Activity Cancer Res., February 15, 2005; 65(4): 1369 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Wollert and H. Drexler Clinical Applications of Stem Cells for the Heart Circ. Res., February 4, 2005; 96(2): 151 - 163. [Abstract] [Full Text] [PDF]
|
|