Methods and devices for detection and therapy of atheromatous plaque

Abstract

The present invention relates to devices for detection and therapy of active atheromatous plaque and / or thin-capped fibro-atheroma ("vulnerable plaque"), using selectively targeted fluorescent, radiolabeled, or fluorescent and radiolabeled compositions. The present invention further relates to methods and devices for detection and theraphy of active atheromatous plaques and / or vulnerable plaques, using selectively targeted beta-emitting compositions, optionally comprising fluorescent compositions.

Description

RELATED APPLICATIONS / PATENTS & INCORPORATION BY REFERENCE[0001] This application is a continuation-in-part application of U.S. application Ser. No. 10 / 163,744, filed on Jun. 4, 2002, which claims priority to U.S. Provisional Application No. 60 / 295,627, filed Jun. 4, 2001, and U.S. Provisional Application No. 60 / 365,673, filed Mar. 15, 2002, the contents of which are expressly incorporated herein by reference. Reference is also made herein to PCT / US98 / 18685, published as WO 99 / 12579 on Mar. 18, 1999, the contents of which are expressly incorporated herein by reference.[0002] Each of the applications and patents cited in this text, as well as each document or reference cited in each of the applications and patents (including during the prosecution of each issued patent; "application cited documents"), and each of the PCT and foreign applications or patents corresponding to and / or claiming priority from any of these applications and patents, and each of the documents cited or reference...

AI Technical Summary

Benefits of technology

[0031] It now been determined that intravascular beta-emitting agents can be detected within atheromatous and / or vulnerable plaques by beta detection devices of the present invention. The use of a beta-emitting composition targeted to the active atheromatous and / or vulnerable plaque should improve detection of the same due to the improved sensitivity and reduced distance necessary to accurately observe the area of the plaque. Beta-emission based methods and devices of the present invention provide accurate delineation of plaque areas, which will improve therapy and fosters early detection.

[0276] In the case where detector 1710 is a beta emitting radioactive detector, stent 1705 may be pulled back a distance that is far enough from detector 1710 while it is working to find the location of the plaque. This may prevent false readings from the radioactive accumulation in the vulnerable plaque. Since beta rays have short ranges in the order of a few millimeters, any affect on the readings of detector 1710 may be prevented by retracting stent 1705 such distances.

Problems solved by technology

Current therapies designed to ameliorate the occlusive effects of atheromatous plaques on coronary blood flow, such as coronary artery bypass surgery and percutaneous transluminal coronary angioplasty, do not always prevent the incidence of acute coronary syndrome.

Even with currently available therapeutic approaches, such as lipid lowering, angioplasty and bypass, an unacceptably high incidence of acute coronary syndrome remains (Sacks et al.

Vascular smooth muscle cells are the major source of extra cellular matrix production, and therefore, the absence of vascular smooth muscle cells from a vulnerable plaque contributes to the lack of density in its fibrous cap.

While the fibrous tissue within the cap provides structural integrity to the plaque, the interior of the atheroma is soft, weak and highly thrombogenic.

In particular, inhibition of extracellular matrix production or degradation of extracellular matrix components adversely impacts the structural composition of the fibrous cap.

Present methods of plaque detection, several of which are discussed herein, are inadequate for detecting the genesis of atheromatous plaque and / or thrombus formation, or processes associated with atheromatous plaque and / or thrombus formation, as well as internal inflammation and infection.

Present methods of plaque detection are also inadequate for detecting vulnerable plaques.

Because angioscopic visualization is limited to the surface of the plaque, it is insufficient for use in detecting actively forming atheromatous and / or vulnerable plaques.

However, none has proven to be sufficiently sensitive to identify vulnerable plaques or monitor the formation thereof.

IVUS can detect thin caps and distinguish regions of intermediate density (e.g., intima that is rich in smooth muscle cells and fibrous tissue) from echolucent regions, but current technology does not determine which echolucent regions are composed of cholesterol pools rather than thrombosis, hemorrhage, or some combination thereof.

However, thermography may not provide information about eroded but non-inflamed lesions, vulnerable or otherwise, having a propensity to rupture.

However, long image acquisition time, high costs, limited penetration and a lack of physiologic data render this approach undesirable for detection of actively forming atheromatous and / or vulnerable plaques.

However, it is unlikely that actively forming and / or vulnerable plaques will be reliably differentiated from stable plaques based solely on this ratio.

All of the existing technologies and methods used to date are structural and therefore may be unable to detect actively forming or vulnerable plaques.

The usefulness of such agents is limited and will not accurately detect plaque or thrombus due to the background activity from the surrounding tissue.

Although 3D imaging via PET and SPECT is presently in use, the small size of the arteries as compared to the scatter from the large surrounding tissues lowers the utility of these imaging modalities as well.

The devices of U.S. Pat. No. 4,995,396 are not designed to identify vulnerable plaques and further, U.S. Pat. No. 4,995,396 does not disclose intra-arterial beta probes.

However, these techniques lack the precision of selective targeting as first described herein.

However, there is generally a relative lack of selectivity of most photosensitizers for atheromatous plaques and more particularly for vulnerable plaques.

Moreover, methods known in the art for photodynamic destruction of atherosclerotic plaques generally fail as a result of the inflammatory response that follows PDT.

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