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

a technology of matrix metalloproteinase and atrial fibrillation, which is applied in the field of evaluating the presence and vulnerability of atrial fibrillation and other indications using matrix metalloproteinase-based imaging, can solve the problems of correlated with increased risk of af and cavd, and achieve the effect of increasing the uptake of imaging agents and increasing risk

Inactive Publication Date: 2015-01-22
LANTHEUS MEDICAL IMAGING INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for detecting and risk-determination for calcific aortic valve disease (CAVD) using an imaging agent. This imaging agent contains an MMP inhibitor linked to an imaging moiety. The method involves administering the imaging agent to a subject and acquiring a cardiac image, which can include the valve and leaflets. The increased uptake of the imaging agent in the aortic valve region is indicative of CAVD or an increased risk of developing CAVD. This method can be used on subjects without symptoms of atherosclerosis, allowing for the imaging of tissue remodeling associated with CAVD.

Problems solved by technology

It has not been heretofore known that MMP levels could be detected at such early time points and that detection at these early time points correlated with increased risk of, for example, AF and CAVD.

Method used

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

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Experimental program
Comparison scheme
Effect test

embodiment 1

(1) In some embodiments, the compound is of embodiment 1 of this first non-limiting set of embodiments, wherein the compound comprises:

a) 1-10 targeting moieties

b) a chelator (Ch); and

c) 0-1 linking groups (Ln) between the targeting moiety and chelator;

wherein the targeting moiety is a matrix metalloproteinase inhibitor; and

wherein the chelator is capable of conjugating to a cytotoxic radioisotope.

(2) A compound according to embodiment 1, wherein the targeting moiety is a matrix metalloproteinase inhibitor having an Inhibitory constant Ki of <1000 nM.

(3) A compound according to embodiment 1, wherein the targeting moiety is a matrix, metalloproteinase inhibitor having an inhibitory constant Ki of <100 nM.

(4) A compound according to any one of embodiments 1-3, comprising 1-5 targeting moieties.

(5) A compound according to embodiment 1, comprising one targeting moiety.

(6) A compound according to any one of embodiments 1-5, wherein the targeting moiety is a matrix metalloproteinase inhib...

embodiment 47

(51) In some embodiments, a radiopharmaceutical wherein the cytotoxic radioisotope is selected from the group consisting of beta particle emitters, alpha particle emitters, and Auger electron emitters.

(52) In some embodiments, a radiopharmaceutical according to embodiment 47 wherein the cytotoxic radioisotope is selected from the group consisting of: 186Re, 188Re, 153Sm, 166Ho, 177Lu, 149Pm, 90Y, 212Bi, 103Pd, 109Pd, 159Gd, 140La, 198Au, 199Au, 169Yb, .sup.175Yb, 165Dy, 166Dy, 67Cu, 105Rh, 111Ag, and 192Ir.

(53) In some embodiments, a radiopharmaceutical according to embodiment 47 wherein the cytotoxic radioisotope is selected from the group consisting of: 186Re, 188Re, 153Sm, 166Ho, 177Lu, 149Pm, 90Y, 212Bi, 103Pd, 105Rh,

(54) In some embodiments, a radiopharmaceutical according to embodiment 47 wherein the cytotoxic radioisotope is selected from the group consisting of: 186Re, 188Re, 153Sm, 166Ho, 177Lu, 149Pm, 90Y, and 212Bi.

(55) In some embodiments, a composition comprising a com...

embodiment 36

(41) A diagnostic agent wherein the paramagnetic metal ion is selected from the group consisting of Gd(III), Dy(III), Fe(III), and Mn(II).

(42). A diagnostic agent according to embodiment 36 wherein the x-ray absorber is a metal is selected from the group consisting of: Re, Sm, Ho, Lu, Pm, Y, Bi, Pd, Gd, La, Au, Au, Yb, Dy, Cu, Rh, Ag, and Ir.

(43) A diagnostic composition comprising a compound according to any one of embodiments 1-42 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

(44) A kit comprising a compound of to any one of embodiments 1-42, or a pharmaceutically acceptable salt form thereof and a pharmaceutically acceptable carrier.

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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.

Description

BACKGROUND OF INVENTION[0001]Atrial fibrillation (AF) is a disturbance in the rhythmic beating (or arrhythmia) of the upper chambers of the heart. AF is the most common sustained cardiac arrhythmia, responsible for almost 50% of hospitalizations for arrhythmias (Benjamin E J, et al. 1998; Wyse D G, et al. 2002; Benjamin E J, et al. 1997; Allessie M A, et al. 2001). Consequently, AF is a significant cause of morbidity and mortality and treatment of AF has been hampered by the ineffectiveness of available drugs. Moreover, attempts to terminate AF with electrical shocks, using a process termed “cardioversion” works for only about one-half of the patients during the first 6-12 months. Therefore, a “simple” means to identify patients in whom cardioversion would effectively terminate AF would be beneficial in terms of saved time and money. Moreover, a means to identify patients that may or may not benefit from an implantable pacer, pharmacological rate and / or rhythm control therapy and / or...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K51/08A61K51/04
CPCA61K51/08A61K51/044A61K51/0476A61K51/0478A61B2576/023A61K51/0459A61K51/0497G16H30/40
Inventor SINUSAS, ALBERT J.AKAR, JOSEPH G.CESATI, RICHARD R.RADEKE, HEIKE S.HABER, STEPHEN B.
Owner LANTHEUS MEDICAL IMAGING INC
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