Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats.
OBJECTIVE
Thrombosis is a leading cause of morbidity and mortality worldwide. Current diagnostic strategies rely on imaging modalities that are specific for distinct vascular territories, but a thrombus-specific whole-body imaging approach is still missing. Moreover, imaging techniques to assess thrombus composition are underdeveloped, although therapeutic strategies may benefit from such technology. Therefore, our goal was to test whether positron emission tomography (PET) with the fibrin-binding probe (64)Cu-FBP8 allows multisite thrombus detection and fibrin content estimation.


RESULTS
Thrombosis was induced in Sprague-Dawley rats (n=32) by ferric chloride application on both carotid artery and femoral vein. (64)Cu-FBP8-PET/CT imaging was performed 1, 3, or 7 days after thrombosis to detect thrombus location and to evaluate age-dependent changes in target uptake. Ex vivo biodistribution, autoradiography, and histopathology were performed to validate imaging results. Arterial and venous thrombi were localized on fused PET/CT images with high accuracy (97.6%; 95% confidence interval, 92-100). A single whole-body PET/MR imaging session was sufficient to reveal the location of both arterial and venous thrombi after (64)Cu-FBP8 administration. PET imaging showed that probe uptake was greater in younger clots than in older ones for both arterial and venous thrombosis (P<0.0001). Quantitative histopathology revealed an age-dependent reduction of thrombus fibrin content (P<0.001), consistent with PET results. Biodistribution and autoradiography further confirmed the imaging findings.


CONCLUSIONS
We demonstrated that (64)Cu-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin can provide, noninvasively, insight into clot composition.
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Francesco
F
Blasi
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Bruno L
BL
Oliveira
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Tyson A
TA
Rietz
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Nicholas J
NJ
Rotile
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Pratap C
PC
Naha
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
David P
DP
Cormode
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
David
D
Izquierdo-Garcia
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.).
Ciprian
C
Catana
From the Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (F.B., B.L.O., T.A.R., N.J.R., D.I.-G., C.C., P.C.); Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (P.C.N., D.P.C.); and Institute for Innovation in Imaging, Massachusetts General Hospital, Boston (P.C.). caravan@nmr.mgh.harvard.edu.
Peter
P
Caravan
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D001707:Biopsy, Needle; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000473:pathology; D051598:Whole Body Imaging / Q000379:methods*
D003301:Copper Radioisotopes; D005337:Fibrin
cardiovascular; diagnostic techniques; fibrin; magnetic resonance imaging; molecular imaging; positron-emission tomography; thrombosis; whole body imaging