Thrombus imaging with fibrin-specific gadolinium-based MR contrast agent EP-2104R: results of a phase II clinical study of feasibility.
OBJECTIVE
To determine the feasibility of detecting thrombi using a fibrin-specific gadolinium-based magnetic resonance imaging contrast agent, EP-2104R.


METHODS
Subjects with confirmed thrombus in the venous system (n = 14), or in the heart, or arterial system (n = 38) were enrolled. Patients were imaged before and at various times following a 4 mumol/kg intravenous bolus injection of EP-2104R: <1 hour (N = 16), 2 to 6 hours (N = 36), and/or 20 to 36 hours (N = 33). Images were assessed by investigators at each site and by a single reader not affiliated with the sites to determine whether thrombi were visible, not visible, or further enhanced with EP-2104R. A subset of data was analyzed quantitatively by measuring a signal intensity relative to background tissue.


RESULTS
Overall, 29 thrombi were visible before contrast administration, 3 of 14 in the venous system, and 26 of 38 in the arteries and heart. Thrombi generally enhanced in signal after EP-2104R injection, and an additional 7 were visualized. After contrast, 4 of 14 thrombi were visible in the venous system, and 32 of 38 in the arteries and heart. Thrombi were more conspicuous when imaged at 2 to 6 hours post EP-2104R compared with within 1 hour, because of lower blood background. Quantitatively, the post: pre signal intensity ratio was 1.90 at 2 to 6 hours post injection (standard deviation = 1.08, N = 20, P < 0.001); and 2.04 (standard deviation = 1.29, N = 19, P < 0.0025) for the 20 to 36 hours time point. There were no serious adverse events considered related to study drug.


CONCLUSIONS
EP-2104R enhanced magnetic resonance imaging detects thrombi not readily visible in precontrast screening and gives additional enhancement of thrombi that are visible in precontrast imaging.
Vymazal
Josef
J
Department of Radiodiagnostic, Hospital Na Homolce, Praha, Czech Republic.
Spuentrup
Elmar
E
Cardenas-Molina
Gerardo
G
Wiethoff
Andrea J
AJ
Hartmann
Michael G
MG
Caravan
Peter
P
Parsons
Edward C
EC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005682:Gadolinium / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013927:Thrombosis / Q000175:diagnosis* / Q000378:metabolism*; D055815:Young Adult
D003287:Contrast Media; C503783:EP-2104R; D010455:Peptides; D005337:Fibrin; D005682:Gadolinium