Thrombus Imaging with a Technetium99m-Labeled, Activated Platelet Receptor-Binding Peptide (original) (raw)
Related papers
Jnm the Journal of Nuclear Medicine, 1994
have long lifetimes in the blood which preclude imaging thrombus-bound tracer over the blood background within the first few hours after injection (1â€"4). Monoclonal anti bodies (Mabs) raised against fibrin or platelets (2,4â€"12) have received attention recently because they have highly specific molecular recognition regions which can be tar geted to specific sites on preformed thrombi. In principle, Mabs can be proteolytically degraded to fragments to in crease the rate of blood disappearance, but experience with antifibrin antibodies has shown that even Fab frag ments usually leave the blood pool too slowly to provide a reliably rapid diagnosis (8). As a potential solution to this problem, it was theorized that synthetic oligopeptides, with to thrombus is not yet sufficient for rellabte Imaging of pta existing thrombi. J Nuci Med1994; 35:282â€"288 ost radiopharmaceuticalswhich have been investi gated for their ability to bind to thrombi have been based on native proteins, antibodies and cells. Native proteins ReceivedMay6, 1989;revIsionnoce@edNov.9, 1989.
Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1995
Scintigraphy, using small, thrombus-avid, synthetic peptides labeled with gamma-emitting nuclides is an innovative approach to the noninvasive detection of acute deep venous thrombosis (DVT). The goal of this study was to evaluate clinically 99mTc-P280 for imaging DVT. The peptide P280 is a 26 amino acid dimer that binds with high affinity to the GPIIb/IIIa receptor expressed on activated platelets and can be labeled with 99mTc. Scintigraphy with 99mTc-P280 (10-22 mCi) was performed in nine patients with clinical suspicion and diagnostic evidence of DVT. Planar and tomographic images of the legs, abdomen/pelvis, chest and head were obtained immediately, 1, 2, 4 and 24 hr after injection. No adverse effects were noted after 99mTc-P280 administration in any patient. Positive visualization of thrombi occurred in eight of nine cases with confirmed DVT within 1 hr of tracer injection. The majority of the patients had recent onset of DVT symptoms (less than 3 wk), while the only negative ...
Circulation, 2000
Background —A diagnostic test that could distinguish between stable and unstable coronary atherosclerotic plaques would be useful. We tested the ability of a new glycoprotein IIb/IIIa platelet inhibitor DMP-444, labeled with technetium (Tc)-99 m, to identify platelet-rich thrombus by nuclear imaging in a canine model. Methods and Results —Combinations of a flow-limiting stenosis and 0 to 15 minutes of endothelial electrical stimulation at a site in the left anterior descending coronary artery were used to induce varying amounts of thrombus formation. In 10 animals with markedly positive nuclear images after the injection of Tc-99m DMP-444, the presence of platelet-rich thrombus was confirmed postmortem by gross appearance, high nuclear counts, and abundant platelets on electron microscopy. The 10 animals with negative images had lower counts, smaller thrombus weights ( P <0.05 for each), and fewer platelets by electron microscopy. Conclusions —Activated platelets participating in...
Evaluation of indium-111-labeled anti-fibrin antibody for imaging vascular thrombi
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1988
Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.
Imaging thrombus with radiolabelled monoclonal antibody to platelets
BMJ, 1986
Indium-III-hydroxyquinoline labelled platelets, though useful in the detection ofthrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a "'In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with "'In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo-that is, by direct intravenous injection of P256-in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The "'In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, 2016
Many patients worldwide suffer from cardiovascular diseases for which an underlying factor is thrombosis. Devising a molecular imaging technique for early detection of thrombosis in a clinical setting is highly recommended. Because fibrin is a major constituent of clots and is present in all types of thrombi but absent in circulation, it is a highly specific and sensitive target for molecular imaging of thrombi. It is assumed that cyclization of peptides will improve the receptor binding affinity and stability of the peptide. In the present study, we have developed linear and cyclic fibrin-binding peptides for thrombus imaging and compared their biological properties. Linear HYNIC-GPRPP and cyclic HYNIC-CGPRPPC peptides were synthesized using a standard Fmoc strategy and radiolabeled with Tc-99m. The stability of the radiolabeled peptides in human plasma and their affinity for fibrin and blood clots were determined. Blood clearance and biodistribution were evaluated in rats and mice...
Circulation, 1992
Background. Contemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis. Methods and Results. We have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiolabeled degradation products from the liver. The rapid clearance of unaltered or PPACK-treated t-PA was not influenced by conjugation to *I-DLT, but the release of radioiodinated degradation products into plasma after injection of *I-DLT-conjugated t-PA was markedly less than release of degradation products of directly radioiodinated t-PA. When 131i-DLT-PPACK-t-PA was infused for 15 minutes intravenously after a bolus injection of 20% in dogswith coronary, pulmonary, or carotid artery thrombi, clearance was rapid. Mean ± SEM thrombus-to-blood ratios of radioactivity were high, ranging from 37+9:1 and 2.8±0.6:1 with carotid thrombi formed concomitantly or approximately 30 minutes before infusion of tracer, respectively, to 35:1 for concomitantly formed coronary thrombi, 42±7:1 and 8.1±0.8:1 for concomitantly formed and preformed pulmonary thrombi, respectively, and 18:1 for a preformed femoral artery thrombus. Thrombi were detectable by planar gamma scintigraphy even though image quality was affected adversely by low concentrations of radioactivity that in aggregate composed a relatively large amount of radioactivity in underlying and overlying tissues. This limitation was overcome by tomographicimaging, which was used to detect both femoral and pulmonary thrombi. Conclusions. Use of enzymatically inactivated t-PA coupled to a residualizing label permits rapid detection and localization of thrombi in vivo. (Circulation 1992;85:288-297) T N hrombolysis is being used increasingly as priwith thrombolytic drugs (-15%) requires rapid nonmary therapy for several thromboembolic invasive detection to facilitate decisions critical in disorders. Its widespread implementation management.' Several radiopharmaceutical candicombined with the relatively high incidence of early dates have been evaluated as potential clot-imaging thrombotic reocclusion in a substantial minority of agents, including`M I-labeled fibrinogen,2 99mTc-lapatients with acute myocardial infarction treated beled plasmin,3 "'I-abeled plasminogen,4 13l11 From the Cardiovascular Division (J.