[64Cu]FBP8 for fibrin imaging

[64Cu]FBP8 is a fibrin specific PET probe currently being developed for evaluation in patients. Thrombosis is often the underlying cause of major cardiovascular diseases including heart attack, stroke, and venous thromboembolism, leading causes of morbidity and mortality. Fibrin is a primary component of thrombi and direct PET imaging of fibrin offers a noninvasive and whole-body approach to thrombus detection. Fibrin is present at high concentrations in both venous and arterial clots but not in circulating blood, resulting in potential high sensitivity and specificity of detection In addition to thrombosis, extravascular fibrin is associated with fibrosis, with many solid tumors, and with acute respiratory distress syndrome.

[64Cu]FBP8 comprises a 6-aminoacid cyclic peptide conjugated to a copper chelator. The peptide has submicromolar affinity for fibrin and high selectivity (>100-fold) for fibrin over fibrinogen or plasma proteins, and this affinity and specificity is maintained in [64Cu]FBP8. In addition to its high affinity for fibrin, [64Cu]FBP8 displays fast blood clearance, and high metabolic stability (J Nucl Med. 2014;55:1157-1163). These properties result in high thrombus:background ratios in PET imaging studies in animal models of arterial and venous thrombosis, pulmonary embolism, and embolic stroke.

The I3 is supporting the development of [64Cu]FBP8 for human studies under the exploratory investigational new drug (IND) mechanism.

Figure. Left: PET image of [64Cu]FBP8 in a rat model of carotid artery thrombosis showing the high focal uptake of the probe in the right carotid artery (arrow) and low background signal. Right: Quantification of probe uptake from PET images demonstrating the very high thrombus to background ratios in the head, neck, and thorax.