Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction.
OBJECTIVE
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 technetium-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.
van den Borne
Susanne W M
SW
University of California, Irvine School of Medicine, Irvine, California, USA.
Isobe
Satoshi
S
Verjans
Johan W
JW
Petrov
Artiom
A
Lovhaug
Dagfinn
D
Li
Peng
P
Zandbergen
H Reinier
HR
Ni
Youping
Y
Frederik
Peter
P
Zhou
Jun
J
Arbo
Bente
B
Rogstad
Astri
A
Cuthbertson
Alan
A
Chettibi
Salah
S
Reutelingsperger
Chris
C
Blankesteijn
W Matthijs
WM
Smits
Jos F M
JF
Daemen
Mat J A P
MJ
Zannad
Faiez
F
Vannan
Mani A
MA
Narula
Navneet
N
Pitt
Bertram
B
Hofstra
Leonard
L
Narula
Jagat
J
D000818:Animals; D002232:Carbocyanines; D003094:Collagen / Q000378:metabolism; D003324:Coronary Artery Disease; D004719:Endomyocardial Fibrosis / Q000150:complications* / Q000000981:diagnostic imaging; D005240:Feasibility Studies; D005347:Fibroblasts; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology*; D016023:Integrins; D008297:Male; D051379:Mice; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D019275:Radiopharmaceuticals; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D020257:Ventricular Remodeling
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D016023:Integrins; D019275:Radiopharmaceuticals; D003094:Collagen