title: Fibrin-targeted PET probes for the detection of thrombi.
abstract: There is an ongoing effort to develop better methods for noninvasive detection and characterization of thrombi. Here we describe the synthesis and evaluation of three new fibrin-targeted positron emission tomography (PET) probes (FBP1, FBP2, FBP3). Three fibrin-specific peptides were conjugated as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-monoamides at the C- and N-termini and chelated with (64)CuCl2. Probes were prepared with a specific activity ranging from 10 to 130 μCi/nmol. Both the peptides and the probes exhibited nanomolar dissociation constants (Kd) for the soluble fibrin fragment DD(E), although the Cu-DOTA derivatization resulted in a 2-3 fold loss in affinity relative to the parent peptide. Biodistribution and imaging studies were performed in a rat model of carotid artery thrombosis. For FBP1 and FBP2 at 120 min post injection, the vessel containing the thrombus showed the highest concentration of radioactivity after the excretory organs, that is, the liver and kidneys. This was confirmed ex vivo by autoradiography, which showed >4-fold activity in the thrombus-containing artery compared to the contralateral artery. FBP3 showed much lower thrombus uptake, and the difference was traced to greater metabolism of this probe. Hybrid MR-PET imaging with FBP1 or FBP2 confirmed that these probes were effective for the detection of an arterial thrombus in this rat model. A thrombus was visible on PET images as a region of high activity that corresponded to a region of arterial occlusion identified by simultaneous MR angiography. FBP1 and FBP2 represent promising new probes for the molecular imaging of thrombi.
authors: A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School , 149 Thirteenth Street, Suite 2301, Charlestown, Massachusetts 02129, USA.
authors: Katie L
authors: KL
authors: Ciesienski
authors: Yan
authors: Y
authors: Yang
authors: Ilknur
authors: I
authors: Ay
authors: Daniel B
authors: DB
authors: Chonde
authors: Galen S
authors: GS
authors: Loving
authors: Tyson A
authors: TA
authors: Rietz
authors: Ciprian
authors: C
authors: Catana
authors: Peter
authors: P
authors: Caravan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005337:Fibrin / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000175:diagnosis*
chemical_list: D005337:Fibrin