EVALUATION OF PRESENCE OF AND VULNERABILITY TO ATRIAL FIBRILLATION AND OTHER INDICATIONS USING MATRIX METALLOPROTEINASE-BASED IMAGING
The invention provides, in some embodiments, methods relating to assessing increased risk of developing atrial fibrillation (AF), and/or the likelihood of responding to particular AF therapies using imaging agents comprising an MMP inhibitor linked to an imaging moiety. The invention further provides methods for evaluating the presence of the risk of developing other cardiovascular conditions and assessing the effectiveness of treatment or other intervention for such conditions by determining MMP levels.
1 . A method of evaluating risk of developing atrial fibrillation comprising
administering to a subject an imaging agent comprising a matrix metalloproteinase (MMP) inhibitor linked to an imaging moiety, and
acquiring a cardiac image of the subject,
wherein a level of the imaging agent in the heart of the subject above control is indicative of an increased risk of developing atrial fibrillation.
2 . The method of claim 1 , wherein
the subject has been previously diagnosed with atrial fibrillation and previously treated for atrial fibrillation.
3 . The method of claim 2 , wherein the atrial fibrillation recurrence is atrial fibrillation recurrence following cardioversion therapy.
4 . A method for identifying a subject having a history of atrial fibrillation that is likely to respond to treatment with an implantable pacer, or pharmacological rate control therapy, or pharmacological rhythm control therapy, or ablation therapy comprising
administering to a subject previously diagnosed with atrial fibrillation an imaging agent comprising a matrix metalloproteinase (MMP) inhibitor linked to an imaging moiety, and
acquiring a cardiac image of the subject,
wherein a level of imaging agent in the heart of the subject above control identifies a subject to be treated with an implantable pacer, or treated with pharmacological rate control therapy, or treated with pharmacological rhythm control therapy, or treated with ablation therapy
5 - 7 . (canceled)
8 . The method of claim 4 , wherein the subject has experienced one AF event.
9 . The method of claim 4 , wherein the subject has experienced recurrent AF.
10 . The method of claim 1 , wherein the cardiac image is an atrial image.
11 . The method of claim 1 , wherein the cardiac image is a left atrial image.
12 . The method of claim 1 , wherein the subject is a human subject.
13 . The method of claim 1 , wherein the subject does not manifest signs associated with myocardial fibrosis.
14 . The method of claim 1 , wherein the subject does not manifest signs associated with myocardial remodeling.
15 . The method of claim 1 , wherein the subject has experienced a myocardial infarction.
16 . The method of claim 1 , wherein the imaging agent is RP805.
17 . The method of claim 1 , wherein the imaging agent is selected from the group consisting of
wherein F represents an isotopically-enriched population of 18 F, and
variants thereof comprising, instead of F, an isotopically-enriched imaging moiety selected from the group consisting of 11 C, 13 N, 123 I, 125 I, 99m Tc, 95 Tc, 111 In, 62 Cu, 64 Cu, 67 Ga, and 68 Ga.
18 . The method of claim 1 , further comprising determining a measure of myocardial perfusion in the subject.
19 . The method of claim 18 , wherein determining a measure of myocardial perfusion in the subject comprises administering to the subject a myocardial perfusion imaging agent and obtaining a myocardial perfusion image to determine a measure of myocardial perfusion.