Evaluation of presence of and vulnerability to atrial fibrillation and other indications using matrix metalloproteinase-based imaging

Abstract

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.

What is claimed is: 
     
         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 . A method for evaluating risk of developing atrial fibrillation recurrence comprising
 administering to a subject previously diagnosed with atrial fibrillation and previously treated for 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 is indicative of an increased risk of atrial fibrillation recurrence. 
     
     
         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, pharmacological rate control therapy, 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. 
     
     
         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 10 , 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.