Image-guided therapy of myocardial disease: composition, manufacturing and applications

Abstract

Compositions and methods for imaging and for chemotherapy and radiotherapy are disclosed. More particularly, the invention concerns agents comprising a targeting moeity comprising a beta-adrenergic receptor targeting compound conjugated or embedded with ethylenediamine. The present invention also concerns methods of application of such agents for imaging and treatment of cardiovascular diseases, and kits for preparing a radiolabeled therapeutic or diagnostic agent.

1 . An agent comprising an esmolol targeting moeity conjugated to an ethylenediamine chelator. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The agent of  claim 1  further comprising a valent metal ion attached to the ethylenediamine. 
     
     
         5 . The agent of  claim 4 , wherein the valent metal ion is selected from the group consisting of Gd, Fe, Tc-99m, Cu-60, Cu-61, Cu-62, Cu-64, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-186, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Bi-212, and Bi-213. 
     
     
         6 . The agent of  claim 4 , wherein the valent metal ion is selected from the group consisting of a therapeutic metal selected from the group consisting of arsenic, cobolt, copper, selenium, thallium, and platinum. 
     
     
         7 . The agent of  claim 1 , further comprising an imaging moiety. 
     
     
         8 . The agent of  claim 7 , wherein the imaging moiety is a contrast media. 
     
     
         9 . The agent of  claim 8 , wherein the contrast media is selected from the group consisting of a CT contrast media, an MRI contrast media, and optical contrast media, and an ultrasound contrast media. 
     
     
         10 . A method of imaging a subject having a cardiovascular disease, comprising:
 a) administering to the subject a composition comprising an effective amount of an agent in accordance with  claim 1 ; and   b) performing imaging using a first imaging modality by detecting a first signal from said agent; and   c) performing imaging using a second imaging modality by detecting a second signal from said agent,   wherein the first imaging modality and the second imaging modality are performed either concurrently or consecutively.   
     
     
         11 . The method of  claim 10 , wherein the first imaging modality and the second imaging modality are each selected from the group consisting of PET, CT, SPECT, MRI, optical imaging, and ultrasound. 
     
     
         12 . The method of  claim 10 , wherein the first imaging modality and the second imaging modality are identical 
     
     
         13 . A method of treating a subject having a cardiovascular disease, comprising:
 a) obtaining a therapeutically effective amount of an agent in accordance with  claim 1 ; and   b) administering to the subject a composition comprising the therapeutically effective amount of the agent.   
     
     
         14 . The method of  claim 10 , wherein the cardiovascular disease is selected from the group consisting of hypertension, cardiopathy, myocardial disease, coronary artery disease, cardiac arrhythmia, congestive heart failure, atrial tachycardia, atrial fibrillation, atrial arrhythmia, ventricular fibrillation, ventricular arrhythmia, premature ventricular heartbeats, ventricular tachycardia, premature ventricular extrasystoles, atrioventricular dissociation, multifocal ectopic beats, bigeminal rhythm, trigeminal rhythm, angina pectoris, coronary insufficiency, sympathetically induced pain and coronary spasm. 
     
     
         15 . A kit for preparing a diagnostic or therapeutic composition comprising a sealed container including a predetermined quantity of an agent in accordance with  claim 1 . 
     
     
         16 . The kit of  claim 15 , further comprising a radionuclide selected from the group consisting of Tc-99m, Cu-60, Cu-61, Cu-62, Cu-67, In-111, Tl-201, Ga-67, Ga-68, As-72, Re-188, Ho-166, Y-90, Sm-153, Sr-89, Gd-157, Bi-212, and Bi-213. 
     
     
         17 . A method of predicting a favorable response to a therapy for a human subject, wherein said method comprising:
 (a) imaging a subject in need of a beta-blocker therapy in accordance with the method of  claim 10 ,   (b) determining if a first imaging intensity ratio of heart/muscle is higher than a second ratio of heart/another non-muscle tissue;   wherein if the first ratio is found to be higher than the second ratio, then the subject will have a favorable response to the beta blocker therapy.