Uptake of hematoporphyrin derivative by atheromatous plaques: Studies in human in vitro and rabbit in vivo

Abstract

Hematoporphyrin derivative, a photosensitive material used to identify and treat neoplastic tissue in humans, has been found to localize in atheromatous plaques in animals and has recently been found in postmortem human atherosclerotic plaques. It is not known whether human plaques take up hematoporphyrin derivative in vivo. In five patients undergoing surgical vascular procedures, specimens containing atheromatous plaques were removed and immediately incubated in autologous oxygenated blood at 37 degrees C with hematoporphyrin derivative at a clinically relevant concentration for 2 hours. On exposure to ultraviolet light, porphyrin fluorescence was noted throughout each plaque, whereas adjacent plaque-free tissue showed no fluorescence. To compare in vitro with in vivo hematoporphyrin derivative uptake by plaques, the fluorescence of three types of arterial lesions (induced by a high cholesterol diet, catheters or balloon injury) was studied in 16 New Zealand White rabbits. Each lesion fluoresced selectively with the same intensity whether hematoporphyrin derivative exposure was performed in vitro or in vivo. Fluorescence microscopy did not show a difference in the pattern of hematoporphyrin derivative fluorescence between in vitro and in vivo specimens. The results suggest that human atheromatous plaques should take up hematoporphyrin derivative in vivo and are, therefore, potentially suitable for photochemical treatment as a new therapeutic approach to atherosclerosis.

Photodynamic Therapy for the Prevention of Intimal Hyperplasia in Balloon-Injured Rabbit Arteries

“…However, it is generally considered that photosensitizers are taken up by proliferating cells, in which DNA synthesis is accelerated, such as cancer cells and migrating SMCs. [9][10][11] Accumulation of HPD was confirmed to coincide with PCNA-positive cells in the intima and media of the injured arteries in the present study. However, as shown by the fact that peak accumulation of HPD in the media occurred 1 week after the vascular injury whereas the peak number of PCNA-positive cells in the media was observed on day 3 after the vascular injury, there was no steady correlation between the amount of HPD accumulated and the number of proliferating SMCs (Fig 2).…”

“…[9][10][11] The photosensitizer remains dormant until it is activated by light of a very specific wavelength. The light that activates the compound is produced by a light source and is often transmitted through specially modified fiber optics.…”

Differential effect of Photofrin II on growth of human smooth muscle cells from nonatherosclerotic arteries and atheromatous plaques in vitro.

“…This is in agreement with recent studies demonstrating an accumulation of porphyrins in atheromatous plaques. 19 Spokojny et al 22 have shown that HpD was selectively concentrated in different types of arterial lesions in the rabbit model, whereas the media of these tissues exhibited no fluorescence, indicating a decreased or complete lack of HpD uptake. Also Okunaka et al 20 have described in detail how HpD was concentrated in atheromatous lesions of the rabbit with characteristic peaks of the fluorescence at 630, 665, and 690 nm wavelengths after exposure to an excimer pulse dye laser, which was Although DHE is regularly used in combination with photoactivation by laser energy, the results of this study indicate that the application of DHE without photoactivation is also possible for a selective inhibition of plaque cell proliferation at concentrations that do not affect smooth muscle cells from nonatherosderotic arteries.…”

“…However, recent studies have shown that atheromatous plaques in humans and animals accumulate HpD. 19 - 22 Moreover, the potential of these drugs for photodynamic therapy of atherosclerosis was recently described for the rabbit model. 23 It is well known that the main cell type of atheromatous plaques is, besides the monocyte/macrophage, the smooth muscle cell, and that smooth muscle cell proliferation and migration from the media into the subendothelial space are key events in the early stages of atherogenesis.…”

In vivo intravascular laser photodynamic therapy in rabbit atherosclerotic lesions using a lateral direction fiber

“…To achieve this, a diffuse type of laser fiber capable of photoradiating the entire circumference of a vascular lumen is currently being used in our laboratory and its efficacy is being evaluated. Regarding the selective concentration of HpD in human atherosclerotic lesions, Spokojny et al [23][24][25] have verified that if excised arteries are incubated with HpD, the HpD concentrates at atherosclerotic sites in the arteries, thus indicating the possibility that HpD would also concentrate in atherosclerotic lesions of human arteries in vivo. However, even in such cases the patient would require protection from exposure to light for ∼1-2 weeks following administration, owing to the light sensitizing effects of this substance.…”