Vascular Photodynamic Therapy Research Articles

Reactive oxygen species explicit dosimetry to predict tumor growth for benzoporphyrin derivative-mediated vascular photodynamic therapy.

.Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate () effects, which impact the photochemical oxygen consumption rate, are not accounted for. In this preclinical study, reacted reactive oxygen species () was investigated as a dosimetric quantity for PDT outcome. The ability of to predict the cure index (CI) of tumor growth, , where and are the growth rate of tumor under PDT study and the control tumor without PDT, respectively, for benzoporphyrin derivative (BPD)-mediated PDT, was examined. Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences ( to ) and in-air fluence rates ( to ) with a BPD dose of and a drug-light interval (DLI) of 15 min. Treatment was delivered with a collimated laser beam of 1-cm-diameter at 690 nm. Explicit measurements of in-air light fluence rate, tissue oxygen concentration, and BPD concentration were used to calculate for . Light fluence rate at 3-mm depth (), determined based on Monte-Carlo simulations, was used in the calculation of at the base of tumor. CI was used as an endpoint for three dose metrics: light fluence, PDT dose, and . PDT dose was defined as the product of the time-integral of photosensitizer concentration and . Preliminary studies show that best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome. The threshold dose for for vascular BPD-mediated PDT using DLI of 15 min is determined to be 0.26 mM and is about 3.8 times smaller than the corresponding value for conventional BPD-mediated PDT using DLI of 3 h.

Immune Responses after Vascular Photodynamic Therapy with Redaporfin.

Photodynamic therapy (PDT) relies on the administration of a photosensitizer (PS) that is activated, after a certain drug-to-light interval (DLI), by the irradiation of the target tumour with light of a specific wavelength absorbed by the PS. Typically, low light doses are insufficient to eradicate solid tumours and high fluence rates have been described as poorly immunogenic. However, previous work with mice bearing CT26 tumours demonstrated that vascular PDT with redaporfin, using a low light dose delivered at a high fluence rate, not only destroys the primary tumour but also reduces the formation of metastasis, thus suggesting anti-tumour immunity. This work characterizes immune responses triggered by redaporfin-PDT in mice bearing CT26 tumours. Our results demonstrate that vascular-PDT leads to a strong neutrophilia (2–24 h), systemic increase of IL-6 (24 h), increased percentage of CD4+ and CD8+ T cells producing IFN-γ or CD69+ (2–24 h) and increased CD4+/CD8+ T cell ratio (2–24 h). At the tumour bed, T cell tumour infiltration disappeared after PDT but reappeared with a much higher incidence one day later. In addition, it is shown that the therapeutic effect of redaporfin-PDT is highly dependent on neutrophils and CD8+ T cells but not on CD4+ T cells.

Reactive oxygen species explicit dosimetry to predict tumor growth for BPD-mediated vascular photodynamic therapy.

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (ϕ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted reactive oxygen species ([ROS]rx) was investigated as a dosimetric quantity for PDT outcome. We studied the ability of [ROS]rx to predict the cure index (CI) after PDT of murine tumors; CI = 1 - k/kctr, where k and kctr are the growth rate of PDT-treated and control(untreated) tumor, respectively. Mice bearing radiation induced fibrosarcoma (RIF) tumors were treated with BPD-mediated PDT at different in-air fluences (22.5, 40, 45, 50, 70 and 100 J/cm2) and in-air ϕ (75 and 150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 15 mins. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate . ϕ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. CI was used as an endpoint for four dose metrics: light fluence, PDT dose, and [ROS]rx. PDT dose was defined as the product of the time-integral of photosensitizer concentration and ϕ at a 3 mm tumor depth. Preliminary studies show that [ROS]rx best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome. The threshold dose for [ROS]rx is determined to be 0.23 mM and is about 4.3 times smaller than the corresponding value for conventional BPD-mediated PDT using DLI of 3 hrs.

Reactive Oxygen Species Explicit Dosimetry (ROSED) of a Type 1 Photosensitizer.

Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

Photodynamic therapy monitoring with optical coherence angiography

Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.

Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model.

In recent decades, accumulating evidence from both animal and clinical studies has suggested that a sufficiently activated immune system may strongly augment various types of cancer treatment, including photodynamic therapy (PDT). Through the generation of reactive oxygen species, PDT eradicates tumors by triggering localized tumor damage and inducing anti-tumor immunity. As the major component of anti-tumor immunity, the involvement of a cell-mediated immune response in PDT has been well investigated in the past decade, whereas the role of humoral immunity has remained relatively unexplored. In the present investigation, using the photosensitizer BAM-SiPc and the CT26 tumor-bearing BALB/c mouse model, it was demonstrated that both cell-mediated and humoral adaptive immune components could be involved in PDT. With a vascular PDT (VPDT) regimen, BAM-SiPc could eradicate the tumors of ∼70% of tumor-bearing mice and trigger an anti-tumor immune response that could last for more than 1 year. An elevation of Th2 cytokines was detected ex vivo after VPDT, indicating the potential involvement of a humoral response. An analysis of serum from the VPDT-cured mice also revealed elevated levels of tumor-specific antibodies. Moreover, this serum could effectively hinder tumor growth and protect the mice against further re-challenge in a T-cell-dependent manner. Taken together, these results show that the humoral components induced after BAM-SiPc-VPDT could assist the development of anti-tumor immunity.

Effects of vascular photodynamic therapy in a newly adapted experimental rat aortic aneurysm model

The hypothesis driving this study was that photodynamic therapy (PDT) may limit abdominal aortic aneurysm growth due to matrix changes. The aortas of 12 rats were incubated with elastase using a newly modified experimental aneurysm model (3.5 mg/ml). Rats were allocated to an elastase-only group (n = 6) to study the elastase-induced aneurysm growth and an elastase ± PDT group to evaluate if PDT limited aneurysm growth (n = 6). PDT was performed with the photosensitizer methylene blue, and thermoneutral laser light (660 nm) was applied (120 J/cm(2), 100 mW/cm(2)) using a diode laser. Four untreated rats served as controls. The arteries were analysed after 4 weeks based on histology, immunohistochemistry and morphometry. This modified rat elastase model led to reproducible aneurysm development with no elastase-induced mortality compared with control animals (circumference, controls: 2.9 ± 0.2 vs. elastase: 5.5 ± 0.9 mm; P < 0.01). PDT after elastase incubation did not inhibit inflammatory cell infiltration. No significant change in the circumference was observed between elastase incubation and PDT treatment after elastase incubation (circumference, elastase: 5.5 ± 0.9 vs. elastase and PDT: 6.1 ± 0.8 mm; P < 0.01). Despite a PDT-induced resistance to protease digestion, PDT did not reduce aortic dilatation in the elastase-treated rat aorta. These findings suggest that PDT may not be a useful modality to prevent aneurysm growth.

Intracutaneous ALA photodynamic therapy: Dose-dependent targeting of skin structures

Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) depends on local drug uptake, metabolism to porphyrins, and depth of light penetration using different wavelengths. Topical ALA-PDT has limited depth of drug penetration. We studied induced porphyrin distribution and PDT after intradermal ALA administration using different drug concentrations followed by high-fluence red light irradiation. Intradermal injections (∼2 mm deep) of ALA concentrations from 0.0005% to 1% were studied in swine to evaluated porphyrin fluorescence before PDT and clinical and histological damage 24 hours after PDT. Porphyrin accumulation was measured by fluorescence microscopy of frozen section. PDT was performed 3 hours after intradermal injections using a 635 nm LED array at a fluence of 200 J/cm2 . Skin responses to PDT were observed grossly and by histology (blind evaluation). Intradermal ALA caused porphyrin accumulation in epidermis, hair follicles (HF), sebaceous glands (SG), sweat glands (eccrine glands, EG and apocrine glands, AG), and subcutaneous fat. Significant differences of fluorescence intensity were observed between different skin structures (P < 0.05), but there was no significant difference comparing HF to SG; epidermis with either HF or SG; and dermis with fat (P > 0.05). Intradermal ALA is potent. ALA concentrations ≥0.25% followed by red light exposures caused a very intense vascular PDT reaction. Moderate doses of injected ALA concentration (∼0.06%), selectively targeted EG. Low doses (≤0.016%) targeted fat; producing fat necrosis with minimal inflammation, manifested both clinically and histologically. In contrast to topical ALA-PDT, intradermal ALA-PDT can effectively photosensitize deep skin structures. Potentially, intradermal ALA-PDT using various ALA concentrations may be useful for treating vascular lesions (malformations, hemangiomas, tumors), EG/AG disorders, fat or deep targets in skin.

Photodynamic therapy of tumors can lead to development of systemic antigen-specific immune response

Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, b-galactosidase (b-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from betagalactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.

Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response

BackgroundThe mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response.Methodology/Principal FindingsWe used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response.ConclusionUnderstanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.

Focal Targeted Therapy Will Be a Future Treatment Modality for Early Stage Prostate Cancer

Focal targeted therapy of early stage prostate cancer (PCa) can ideally facilitate the concept of personalized medicine in contemporary surgical oncology. To present indications and outcomes of subtotal glandular ablation. This treatment approach aims at the elimination of the cancer with preservation of uninvolved tissue in an attempt to maintain a patient's quality of life (QoL), including undisturbed erectile function as well as urinary and bowel control. In 2002, the idea of a “lumpectomy” using an organ-sparing approach for very localized PCa was proposed in parallel with organ-sparing breast cancer treatment in women. Since then, a few pilot clinical studies have demonstrated an acceptable short-term cancer control while minimizing the complication rate. At the same time, progress in PCa screening has led to a significant stage and tumor volume migration toward early stage disease. In the past few years, a collection of accumulated data has created a scientific background for further development of this concept toward a wider implementation into clinical practice. In this paper, we review all available literature from PubMed of the past 15 yr—from 1994 to 2008—including the terms localized prostate cancer, focal therapy, organ preservation, and morbidity. Several factors were identified that need to be taken into account to further develop an organ-sparing treatment approach for early stage localized PCa and turn this concept into clinical practice. First, novel thermoablative techniques such as third-generation cryosurgery, high-intensity focused ultrasound (HIFU), vascular photodynamic therapy and, electroporation can precisely target a tumor lesion within the prostate while maintaining the integrity of the surrounding tissues. Second, new ultrasound, magnetic resonance imaging (MRI) and molecular imaging techniques may provide new means to detect small PCa lesions. Third, extended image-guided biopsy protocols using a transperineal rather than a transrectal approach can provide a more exact spatial distribution of PCa lesions within the prostate. Fourth, careful patient selection using an individualized approach is a prerequisite for optimal preoperative planning and a successful treatment outcome. For patients with early stage localized PCa limited to one focus or lobe and who express a great desire not to jeopardize their QoL, targeted focal therapy will likely play a more significant role in the future as a tangible treatment option. Moreover, focal therapy may fill the gap between active surveillance for low-risk PCa and radical treatment for higher-risk forms. Focal targeted therapy is becoming an attractive and tangible treatment option for patients with early stage localized prostate cancer limited to one focus or lobe and who are interested in maintaining a higher quality of life.

Platelet Adhesion to Photodynamic Therapy-treated Extracellular Matrix Proteins¶

Photodynamic therapy (PDT) produces reactive species that alter vascular wall biology and vessel wall proteins. In this study, we examined platelet adhesion to PDT-treated (photosensitizer = Photofrin; fluence 100 J/cm2; λ= 630 nm) extracellular matrix (ECM), fibrinogen, von Willebrand factor (vWF) and collagen Types I and III, under flow conditions in a recirculating perfusion chamber. Platelet adhesion was quantified by image analysis. The effect of PDT on vWF was assessed by measuring the binding of domain-specific antibodies to treated vWF. PDT significantly decreased platelet adhesion to the ECM, fibrinogen and vWF. However, PDT of collagen resulted in significantly increased platelet adhesion, with large aggregate formation. PDT affected mostly the A1 (glycoprotein [GP]-Ib–binding site), A2 and A3 (collagen-binding site) domains of vWF but not the D'-D3 (factor VIII–binding site) and B-C1 (GP-IIb/IIIa–binding site) domains. In conclusion, PDT can alter the ECM, resulting in decreased platelet adhesion. However, vessels with high collagen content, such as veins and small arteries, may become increasingly prone to thrombosis. The results of this study may thus play a role in understanding the thrombogenic properties and mechanisms of vascular PDT.

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Flexible treatments for intimal hyperplasia after angioplasty are still needed. The aim of this study was to demonstrate the long-term effects of vascular photodynamic therapy with talaporfin sodium on intimal hyperplasia following interventional injury. Intimal hyperplasia was induced by balloon distension injury to the carotid artery in 31 rabbits. Talaporfin, 5.0 mg/kg, was delivered systemically immediately after balloon injury. The injury site was irradiated with a diode laser light of wavelength 664 nm using a fluence of 50 J/cm2 after 30 min. At day 3 and weeks 3, 6, 9, 15, and 25 after photodynamic therapy, the treated artery of each rabbit was excised and examined immunohistochemically. Thirty minutes after talaporfin administration, drug fluorescence was found only in the balloon-injured carotid artery wall. At 3 days, no smooth muscle cells were seen in the media of the photodynamic therapy-treated arterial segments. Intimal hyperplasia developed progressively in the balloon-injured and untreated segments; however, in the segments treated with photodynamic therapy, intimal hyperplasia was markedly suppressed until 25 weeks and the media was repopulated by smooth muscle cells without macrophages. Vascular photodynamic therapy with talaporfin may be used to inhibit restenosis after vascular intervention.

Arterial wall strength after endovascular photodynamic therapy.

Vascular photodynamic therapy (PDT) inhibits intimal hyperplasia (IH) induced by angioplasty in rat iliac arteries by eradicating the proliferating smooth muscle cells. This process may jeopardise the structure and strength of the arterial wall, reflected by a decreased bursting pressure. Thirty male Wistar rats of 250-300 g were subdivided into 3 groups (n = 10). In all groups, IH was induced by balloon injury (BI). One experimental group received PDT at 50 J/cm diffuser length, the other group at 100 J/cm diffuser length. The third group served as control group and received no PDT. In half of each group the bursting pressure was analyzed after 2 hours (n = 5), in the other half after 1 year. Two hours after the procedure the bursting pressure was 3.37 +/- 0.58 (+/-SEM) bar in the BI + PDT 50 and 3.96 +/- 0.43 bar in the BI + PDT 100 group, compared to 2.20 +/- 0.27 bar in the BI group (P < 0.05). After 1 year these values were 3.18 +/- 0.87 bar in the BI + PDT 50 (P < 0.05) and 2.02 +/- 0.31 bar in the BI + PDT 100 group, compared to 2.10 +/- 0.30 bar in the BI group (NS). In the BI + PDT 100 group, 3 out of 5 rats appeared to have aneurysmal dilatation after 1 year. Endovascular PDT increases the arterial wall strength as measured by the bursting pressure at short-term. After 1 year, wall strength is not diminished as measured by bursting pressure, but aneurysmal dilatation nevertheless developed with 100 J/cm. dl. This may limit the use of high energy PDT.

Platelet adhesion to photodynamic therapy-treated extracellular matrix proteins.

Photodynamic therapy (PDT) produces reactive species that alter vascular wall biology and vessel wall proteins. In this study, we examined platelet adhesion to PDT-treated (photosensitizer = Photofrin; fluence 100 J/cm2; lambda = 630 nm) extracellular matrix (ECM), fibrinogen, von Willebrand factor (vWF) and collagen Types I and III, under flow conditions in a recirculating perfusion chamber. Platelet adhesion was quantified by image analysis. The effect of PDT on vWF was assessed by measuring the binding of domain-specific antibodies to treated vWF. PDT significantly decreased platelet adhesion to the ECM, fibrinogen and vWF. However, PDT of collagen resulted in significantly increased platelet adhesion, with large aggregate formation. PDT affected mostly the A1 (glycoprotein [GP]-Ib-binding site), A2 and A3 (collagen-binding site) domains of vWF but not the D'-D3 (factor VIII-binding site) and B-C1 (GP-IIb/IIIa-binding site) domains. In conclusion, PDT can alter the ECM, resulting in decreased platelet adhesion. However, vessels with high collagen content, such as veins and small arteries, may become increasingly prone to thrombosis. The results of this study may thus play a role in understanding the thrombogenic properties and mechanisms of vascular PDT.

Photodynamic Therapy Induces Apoptosis in Intimal Hyperplastic Arteries

Photodynamic therapy (PDT) generates free radicals through the absorption of light by photosensitizers. PDT shows promise in the treatment of intimal hyperplasia, which contributes to restenosis, by completely eradicating cells in the vessel wall. This study investigates the mechanisms of PDT-induced cell death. PDT, using the photosensitizer chloroaluminum-sulfonated phthalocyanine (1 mg/kg) and laser light (lambda = 675 nm) 100 J/cm(2) was administered to rat carotid arteries after balloon injury-induced intimal hyperplasia. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy, DNA cleavage by terminal dUTP nick-end labeling staining, and nucleosomal fragmentation (ladder pattern) by DNA agarose gel electrophoresis. Four hours after PDT, apoptosis was observed in vascular cells, as evidenced by terminal dUTP nick-end labeling staining and transmission electron microscopy. Within 24 hours no cells were present in the neointima and media. Immunofluorescence using an alpha-smooth muscle cell actin antibody confirmed the disappearance of all neointimal and medial cells within 24 hours. No inflammatory cell infiltrate was observed during this time frame. Apoptosis was sharply confined to the PDT treatment field. These data demonstrate that vascular PDT induces apoptosis as a mechanism of rapid, complete, and precise cell eradication in the artery wall. These findings and the lack of inflammatory reaction provide the basis for understanding and developing PDT for a successful clinical application in the treatment of hyperplastic conditions such as restenosis.

Importance of the Treatment Field for the Application of Vascular Photodynamic Therapy to Inhibit Intimal Hyperplasia

Intimal hyperplasia (IH) plays a dominant role in the development of restenosis. In previous studies, photodynamic therapy (PDT) prevented IH induced by segmental balloon injury of the rat carotid. The critical elements required to control IH effectively with this technique are not fully understood. This study assessed the importance of the treatment field by studying the repair process of injured vessels, in which the PDT-treatment field did not target the entire injured area. The entire rat common carotid artery was balloon-injured to induce IH, whereas only the cervical segment below the bifurcation was subjected to PDT by external light irradiation after administration of the photosensitizer chloroaluminum sulfonated phthalocyanine. Light irradiation of injured arteries without photosensitizer served as control for PDT, and PDT of uninjured arteries was included as a control group for the balloon injury. Histologic characterization of the repair process was sequentially assessed. Balloon-injured arteries without PDT displayed rapid IH development with a peak at 2 weeks. Photodynamic therapy of balloon-injured arteries resulted in complete local depletion of medial smooth muscle cells (SMC), which was associated with a lack of IH until 2 weeks. However, at 4 and 16 weeks there was significant IH in PDT-treated arteries despite a lack of medial SMC repopulation. A wave of IH progression over the acellular media was observed in these arteries, migrating from the injured non-PDT-treated area. The PDT of uninjured arteries did not result in IH and was also associated with a persistent acellular media. Delayed IH development after PDT of injured vessels can result from IH progression from an injured site not included in the treatment field. This also indicated that the source of cells developing the intimal hyperplasia lesion can originate from an area remote from the lesion. Together with previous results and the determination that PDT itself does not induce IH, it can be reasoned that inclusion of the whole injured artery or a section of an uninjured margin in the treatment field is essential for effective PDT prevention of IH.

Importance of the Treatment Field for the Application of Vascular Photodynamic Therapy to Inhibit Intimal Hyperplasia

Importance of the Treatment Field for the Application of Vascular Photodynamic Therapy to Inhibit Intimal Hyperplasia