Author + information
- Received April 30, 2008
- Revision received July 31, 2008
- Accepted July 31, 2008
- Published online December 9, 2008.
- Susanne W.M. van den Borne, MD⁎,†,
- Satoshi Isobe, MD, PhD⁎,
- Johan W. Verjans, MD⁎,
- Artiom Petrov, PhD⁎,
- Dagfinn Lovhaug, MSc‡,
- Peng Li, MD, PhD⁎,
- H. Reinier Zandbergen, MD⁎,
- Youping Ni, MD, PhD⁎,
- Peter Frederik, PhD†,
- Jun Zhou, MD⁎,
- Bente Arbo, PhD‡,
- Astri Rogstad, PhD‡,
- Alan Cuthbertson, PhD‡,
- Salah Chettibi, PhD‡,
- Chris Reutelingsperger, PhD†,
- W. Matthijs Blankesteijn, PhD†,
- Jos F.M. Smits, PhD†,
- Mat J.A.P. Daemen, MD, PhD†,
- Faiez Zannad, MD, PhD, FACC§,
- Mani A. Vannan, MD, FACC⁎,
- Navneet Narula, MD⁎,
- Bertram Pitt, MD, FACC∥,
- Leonard Hofstra, MD, PhD† and
- Jagat Narula, MD, PhD, FACC⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Jagat Narula, Division of Cardiology, University of California, Irvine School of Medicine, 101 The City Drive, Building 53, Mail Route 81, Orange, California 92868-4080
Objectives The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts.
Background Collagen deposition and interstitial fibrosis contribute to cardiac remodeling and heart failure after myocardial infarction (MI). Evaluation of myofibroblastic proliferation should provide indirect evidence of the extent of fibrosis.
Methods Of 46 Swiss-Webster mice, MI was induced in 41 by coronary artery occlusion, and 5 were unmanipulated. Of the 41 mice, 6, 6, and 5 received intravenous technitium-99m labeled CRIP for micro–single-photon emission computed tomography imaging 2, 4, and 12 weeks after MI, respectively; 8 received captopril or captopril with losartan up to 4 weeks after MI. Scrambled CRIP was used 4 weeks after MI in 6 mice; the remaining 10 of 46 mice received unradiolabeled CRIP for histologic characterization.
Results Maximum CRIP uptake was observed in the infarct area; quantitative uptake (percent injected dose/g) was highest at 2 weeks (2.75 ± 0.46%), followed by 4 (2.26 ± 0.09%) and 12 (1.74 ± 0.24%) weeks compared with that in unmanipulated mice (0.59 ± 0.19%). Uptake was higher at 12 weeks in the remote areas. CRIP uptake was histologically traced to myofibroblasts. Captopril alone (1.78 ± 0.31%) and with losartan (1.13 ± 0.28%) significantly reduced tracer uptake; scrambled CRIP uptake in infarct area (0.74 ± 0.17%) was similar to CRIP uptake in normal myocardium.
Conclusions Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling, and is responsive to antiangiotensin treatment. If proven clinically feasible, such a strategy would help identify post-MI patients likely to develop heart failure.
- interstitial fibrosis
- radionuclide imaging
- heart failure
- coronary artery disease
Dagfinn Lovhaug and Drs. Arbo, Rogstad, Cuthbertson, and Chettibi, who prepared the tracer for the imaging studies, are employees of GE Healthcare. Dr. Pitt is a consultant to Pfizer, Merck, Takeda, AstraZeneca, Synvista, Novartis, and Nile Therapeutics, but has no conflicts directly with the project. Dr. van den Borne was supported by a grant from the Van Walree Fund of the Royal Netherlands Academy of Arts and Sciences. Dr. Verjans was partially supported by the DiPalma-Brodsky research grant to Dr. Jagat Narula. CRIP and scrambled CRIP were kindly provided to Dr. Jagat Narula by GE Healthcare, Oslo, Norway. Drs. van den Borne and Isobe contributed equally to this study. Joel S. Karliner, MD, served as Guest Editor for this article.
- Received April 30, 2008.
- Revision received July 31, 2008.
- Accepted July 31, 2008.
- American College of Cardiology Foundation