Intravascular detection of inflamed atherosclerotic plaques using a fluorescent photosensitizer targeted to the scavenger receptor.

Inflammation plays an important role in the pathophysiology of atherosclerotic disease. We have previously shown that the targeted photosensitizer chlorin (e(6)) conjugated with maleylated albumin (MA-ce6) is taken up by macrophages via the scavenger receptor with high selectivity. In a rabbit model of inflamed plaque in New Zealand white rabbits via balloon injury of the aorto-iliac arteries and high cholesterol diet we showed that the targeted conjugate showed specificity towards plaques compared to free ce6.

In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients.

Objectives: Given the importance of inflammation in atherosclerosis, we sought to determine if atherosclerotic plaque inflammation could be measured noninvasively in humans using positron emission tomography (PET).

Background: Earlier PET studies using fluorodeoxyglucose (FDG) demonstrated increased FDG uptake in atherosclerotic plaques. Here we tested the ability of FDG-PET to measure carotid plaque inflammation in patients who subsequently underwent carotid endarterectomy (CEA).

Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorin(e6).

We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits.

Corticosteroid modulation of human, antigen-specific Th1 and Th2 responses.

Corticosteroids are potent antiinflammatory agents that modulate human T-lymphocyte responses. Controversy remains as to their possible differential effects on Th1 and Th2 subsets. This study explores the kinetics and efficacy of these agents in human, antigen-driven peripheral blood mononuclear cells (PBMCs) and in nontransformed, antigen-specific Th1 and Th2 clones.

Differential regulation of human, antigen-specific Th1 and Th2 responses by the B-7 homologues, CD80 and CD86.

A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD86) for promoting Th2 responses in the murine system has recently been suggested.