Imaging Thrombosis with 99m Tc-labeled RAM.1-Antibody in vivo

2018 
Abstract Introduction Platelets play a major role in thrombo-embolic diseases, notably by forming a thrombus that can ultimately occlude a vessel. This may provoke ischemic pathologies such as myocardial infarction, stroke or peripheral artery diseases, which represent the major causes of death worldwide. The aim of this study was to evaluate the specificity of radiolabeled Rat-Anti-Mouse antibody (RAM.1). Methods We describe a method to detect platelets by using a RAM.1 coupled with the chelating agent hydrazinonicotinic acid (HYNIC) conjugated to 99m Tc, for Single Photon Emission Computed Tomography (SPECT). To induce platelet accumulation at a site of interest, we used a mouse model of FeCl 3 induced injury of the carotid artery. 90 min after i . v . injection of [ 99m Tc][Tc(HYNIC)-RAM.1], biodistribution of the radiolabeled RAM.1 was assessed, SPECT imaging and histological analysis were performed on the mice that underwent FeCl 3 -induced vessel damage. Results We demonstrated a quick and strong affinity of the radiolabeled RAM.1 for the platelet thrombus. Results clearly demonstrated the ability of this radioimmunoconjugate for detecting thrombi from 10 min post injection with an exceptional thrombi uptake. Using FeCl 3 , the median ratio between the thrombus and the background was 12.4 (range 9.3–42.3) as compared to 1.0 (range: 0.86–2.7) p Conclusion Thanks to the high sensitivity of SPECT, we provided evidence that [ 99m Tc][Tc(HYNIC)-RAM.1] represents a powerful tool to detect localized platelet thrombi which could potentially be used in humans. Because of the relative low cost and high sensitivity, these results encourage further study like the detection of non-induced thrombus and further developments toward clinical application. This is further supported by the fact that RAM.1 recognizes human platelets.
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