Molecular MR imaging of human thrombi in a swine model of pulmonary embolism using a fibrin-specific contrast agent.
OBJECTIVE
Molecular targeted MR imaging of human clots material in a model of pulmonary embolism using a fibrin-specific magnetic resonance imaging contrast agent (EP-2104R, EPIX Pharmaceuticals, Cambridge, MA).


METHODS
Fresh ex vivo engineered thrombi (human blood) and human clots removed from patients were delivered in 11 swine. Molecular MR imaging with a 3D gradient-echo [3D fast field echo (3DFFE)] sequence and a navigator-gated and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence (IR) was performed before thrombus delivery, after thrombus delivery but before contrast media application, and 2 hours after i.v. administration of 4 micromol/kg EP-2104R. MR images were analyzed by 2 investigators and contrast-to-noise ratio (CNR) was assessed. Thrombi were removed for assessment of gadolinium (Gd) concentration.


RESULTS
Only after contrast media application were pulmonary emboli [freshly engineered thrombi (n = 23) and human clot material removed from patients (n = 25)] visualized as white foci on MR images. CNR was 13 +/- 3 (ex vivo engineered clot) and 22 +/- 9 (patient clot material) for the fast field echo (FFE)-sequence and 29 +/- 9 (ex vivo engineered clot) and 43 +/- 18 (patient clot material) for the IR-sequence, respectively. A high Gd concentration in the clots was found (82 +/- 43 microM for the freshly engineered and 247 +/- 44 microM for the clots removed from patients, respectively).


CONCLUSIONS
EP-2104R allows for molecular MR imaging of human clot material in the pulmonary vessels of a swine model.
Spuentrup
Elmar
E
Departments of Diagnostic Radiology, Aachen Technical University, Aachen, Germany. spuenti@rad.rwth-aachen.de
Katoh
Marcus
M
Buecker
Arno
A
Fausten
Bernd
B
Wiethoff
Andrea J
AJ
Wildberger
Joachim E
JE
Haage
Patrick
P
Parsons
Edward C
EC
Botnar
Rene M
RM
Graham
Philip B
PB
Vettelschoss
Manfred
M
Günther
Rolf W
RW
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011655:Pulmonary Embolism / Q000175:diagnosis* / Q000378:metabolism; D013552:Swine
D003287:Contrast Media; C503783:EP-2104R; D010455:Peptides; D005337:Fibrin; D005682:Gadolinium