Vascular-targeted Photodynamic Therapy Research Articles

Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks

Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. To compare clinical outcomes of PDT and PDL treatment of PWS. Two adjacent flat areas of PWS lesions were selected from each of 15 patients (two male and 13 female; age 11-36 years) and randomly assigned to either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser. PDT was carried out with a combination of haematoporphyrin monomethyl ether (HMME) and a low-power copper vapour laser (510.6 and 578.2 nm). Clinical outcomes were evaluated colorimetrically and visually during follow-up. A total of nine red PWS lesions and six purple PWS lesions were treated. For red PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2 months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS, blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%, respectively. Overall, there was a significant difference between the blanching effect of single-session PDL treatment and a single-session PDT treatment. This side-by-side comparison demonstrates that PDT is at least as effective as PDL and, in some cases, superior. The true value of PDT for the treatment of PWS deserves further investigation.

Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer

BackgroundFocal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease. ObjectiveTo assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management. Design, setting, and participantsFrom 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D’Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP). Outcome measurements and statistical analysisComplications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed. Results and limitationsThis study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61–73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5–8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43g (IQR: 33–55). The median International Prostate Symptom Score was 6 (IQR: 3–10), and the median International Index of Erectile Function score was 20 (IQR: 15–23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2–5.1, 1.1–4.7, and 1–4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications. ConclusionsFT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications.

Drivers for change in the management of prostate cancer – Guidelines and new treatment techniques

Clinical practice guidelines and new treatment techniques are of particular importance for the effective management of prostate cancer. In Europe, the European Association of Urology guidelines offer a regularly updated evidence-based source of recommendations for the optimal treatment of prostate cancer. This review examines recent changes to guidelines highlighting developments in diagnosis, hormonal therapy in advanced and metastatic disease, bone protection, the definition of new terminology such as castrate-resistant prostate cancer, treatment of relapse after hormonal therapy, and cytotoxic therapy for castrate-resistant prostate cancer. The review also examines new surgical and radiotherapeutic developments in prostate cancer. This includes minimally invasive techniques such as robot-assisted radical prostatectomy, which is becoming the surgical gold standard for clinically localized disease in many countries. Other promising techniques reviewed include cryosurgical ablation of the prostate, laser-induced interstitial thermotherapy, vascular-targeted photodynamic therapy, and high-intensity focused ultrasound; with the exception of cryotherapy, these approaches are not currently recommended for routine clinical use. Finally, we will review the evidence supporting intensity modulated radiotherapy, an optimized high-precision form of three-dimensional conformal radiotherapy which aims to allow homogeneously increased radiation doses, without increased toxicity to healthy at-risk organs. Novel techniques such as proton beam or carbon ion radiotherapy, which may offer improved and more localized dose distribution with reduced damage to normal tissue, are also examined.

Combination of Phosphatidylinositol 3‐Kinases Pathway Inhibitor and Photodynamic Therapy in Endothelial and Tumor Cells

Tumor recurrence due to incomplete eradication of tumor cells is a major problem facing current cancer therapies. To overcome this problem, it is necessary to enhance cell killing and/or prevent cell regrowth after treatment. Because phosphatidylinositol 3-kinases (PI3K) pathway plays an important role in stimulating cell survival and growth, we studied the feasibility of using a PI3K pathway inhibitor NVP-BEZ235 (BEZ235) to enhance the effectiveness of vascular-targeted photodynamic therapy (vPDT) with verteporfin. We found that BEZ235 or PDT alone significantly inhibited cell growth in both SVEC endothelial and PC-3 prostate cancer cells, although SVEC cells appeared to be more responsive than PC-3 cells. Autophagy was detected after both BEZ235 and verteporfin-PDT in both cell lines. Autophagy appeared to protect cells from PDT-induced cell death because inhibition of autophagy increased cell death. Autophagic flux assay revealed that PDT actually decreased autophagic flux especially at a high dose of verteporfin. Combination of BEZ235 and PDT caused greater inhibition of PI3K signaling pathway, leading to enhanced cell growth inhibition in both cell lines. SVEC cells exhibited a higher sensitivity towards such a combination than PC-3 cells. Our data indicated that BEZ235 in combination with PDT provides a promising approach of enhancing therapeutic response.

Monitoring Microcirculation Changes in Port Wine Stains During Vascular Targeted Photodynamic Therapy by Laser Speckle Imaging

This study was conducted to test laser speckle perfusion imaging (LSPI) for imaging microcirculation and monitoring microcirculatory changes of port wine stains (PWS) during vascular targeted photodynamic therapy (V-PDT). Before and 5 min after V-PDT, PWS lesions and the corresponding contralateral healthy skins of 24 PWS patients were scanned, whereas seven PWS patients were scanned throughout V-PDT. V-PDT was conducted immediately after intravenous injection of photocarcinorin (4-5 mg kg(-1)). A 532 nm laser was used for irradiation (power density: 80-100 mW cm(-2), exposure time: 20-50 min). Before V-PDT, all 24 PWS patients demonstrated a significant difference in perfusion between the PWS lesion and the contralateral healthy control skin (1132 ± 724 and 619 ± 478 PU, respectively, P < 0.01). Five minutes after V-PDT, the mean perfusion value of the 24 PWS lesions was 1246 ± 754 PU. There was no significant difference compared to the perfusion before V-PDT (P > 0.05). During V-PDT, the perfusion of seven PWS patients increased rapidly after initiation of V-PDT, reached a maximum within 10 min, lasted for several minutes, and slowly returned to a relatively lower level at the end of V-PDT. On the basis of these results, LSPI is capable of imaging PWS microvasculature and monitoring microvascular reactivity to V-PDT.

Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities.

Multifunctional Peptide-Conjugated Hybrid Silica Nanoparticles for Photodynamic Therapy and MRI

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

Vascular targeted photodynamic therapy for bleeding gastrointestinal mucosal vascular lesions: A preliminary study

Vascular-targeted photodynamic therapy (V-PDT) has shown good selectivity and efficacy in the treatment of certain types of vascular disease, including port wine stains, age-related macular degeneration, and esophageal varices. This study was conducted to test the efficacy and safety of V-PDT in the treatment of gastrointestinal (GI) bleeding caused by the abnormal dilatation of capillaries. Patients with bleeding GI mucosal vascular lesions treated with V-PDT were included in this retrospective study. The efficiency of V-PDT was analyzed by comparing the documented endoscopy results, hemoglobin levels, and transfusion requirements before and at 6 months after the last V-PDT. Side effects during and after V-PDT and follow-up results were also analyzed. Seven patients with bleeding GI mucosal vascular lesions were treated with V-PDT. After 1-4 V-PDT sessions, all patients no longer needed transfusions to maintain a stable hemoglobin level during the follow-up period of 6 months. The mean hemoglobin level of the seven patients improved from 6.21±1.48 g/dl to 11.66±1.21 g/dl (p<0.001), and the GI bleeding and melena of all the patients disappeared. No perforations, strictures, scars, or episodes of photosensitization occurred in the seven patients, and there were no recurrences of GI bleeding during the 1-21 months of further follow-up. This preliminary study indicated that V-PDT is a highly selective, safe, well-tolerated, and effective treatment modality for bleeding GI mucosal vascular lesions. However, prospective studies with larger sample sizes are needed to confirm this finding.

Photodynamic therapy of port-wine stains: Long-term efficacy and complication in Chinese patients

Port-wine stain (PWS) are congenital vascular malformations characterized by ectatic capillaries in the papillary layer of the dermis. They usually appear at birth and tend to become darker and thicker with age. Many clinicians consider the gold standard to treat PWS is pulsed dye laser (PDL) with wavelengths of 585 nm or 595 nm. But PDL is not suitable for patients with Fitzpatrick skin type V or nodular lesions. Vascular-targeted photodynamic therapy (PDT) might be an alternative approach in the treatment of such patients. The objective of this study was to assess the long-term outcomes and complications of PDT therapy of PWS in Chinese patients retrospectively. Patients with PWS who had received PDT therapy in a 5-year period were reviewed. 642 patients and a total of 3066 treatment sessions had been performed with an average of 2.6-8.2 sessions. Over 5% of patients had complete clearing, while 70% of patients had more than 25% of clearing. More than one-quarter of patients (29.8%) experienced a clearing of more than 50%. Ten percent of patients experienced complications (1.4% blistering, 1.2% hypopigmentation, 4.3% hyperpigmentation, 2.2% scabbing, <0.7% prolonged blistering that persisted for >2 months, 0.4% eczema dermatitis, 0.6% photoallergy). Sex, age, number of treatment sessions, average energy density and type of skin were not related to complication rate using the multiple regression analysis. Chinese patients were well responsive to and satisfied with vascular-targeted PDT (Patient Satisfaction Score 7.8). Dark-skinned patients and patients with vascular papules or nodules can be treated with alternative PDT to significant therapeutic effect in Chinese patients even though they experience few complications.

Twenty Years of Clinical Experience with a New Modality of Vascular-Targeted Photodynamic Therapy for Port Wine Stains

Port wine stains (PWS) are congenital capillary malformations of the skin and are difficult to treat without scarring. Since January 1991, our group has performed a new modality of vascular-targeted photodynamic therapy (PDT) for PWS treatment. To summarize our clinical experiences with vascular-targeted PDT for PWS at Chinese PLA General Hospital. Our group has collected and reviewed retrospective clinical research data of vascular-targeted PDT for treating PWS since January 1991. Clinical studies showed that vascular-targeted PDT is an effective treatment for all types of PWS. Repetitive treatment sessions were usually needed to obtain a better cosmetic effect. No recurrence was seen in patients followed up for longer than 19 years. There were no significant side effects or adverse reactions. This new PDT is an effective, safe, and noninvasive modality with no recurrence for PWS, although the protocol for PDT requires further optimization.

Treatment Effects in the Prostate Including Those Associated With Traditional and Emerging Therapies

Classic treatment options for prostate cancer consist of radical prostatectomy, antiandrogen (or hormonal) therapy, and radiation therapy. Hormonal and radiation therapy, in particular, have well known, often profound effects on the histologic appearance of benign prostate tissue and prostatic carcinoma. The tissue changes induced by these treatments have been comprehensively described in several sources. Novel therapies ranging from focal ablative treatments to highly targeted molecular therapies are beginning to emerge and pathologists will play a central role in documenting the effects of these treatments on normal and malignant prostate tissue. It is therefore important that pathologists have access to basic treatment information and a solid working knowledge of the morphologic changes induced by these therapies. This will ensure accurate interpretation and reporting of posttreatment prostate specimens. This review is based on a presentation given by Dr A. Evans at the International Society of Urological Pathology Companion Society Meeting (Hot Topics in Urological Pathology) at The United States Canadian Academy of Pathology Meeting in Washington DC on March 20, 2010. This review will cover the histopathologic features seen in benign prostate tissue and prostatic carcinoma seen following: hormonal therapy, radiation therapy, ablative therapies such as vascular-targeted photodynamic therapy, interstitial laser thermotherapy, and high-intensity focussed ultrasound. An emphasis is placed on these specific modalities as they are currently in use as primary, salvage, or investigational therapy in the treatment of prostate cancer.

Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate

Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy. Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week. No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate. The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia.

Antitumor immunity promoted by vascular occluding therapy: lessons from vascular-targeted photodynamic therapy (VTP)

The development of cancer is tightly related to the successful evasion of neoplastic tissue from immune system surveillance, which represents a key obstacle in tumor therapy. Most conventional therapies (surgery, chemotherapy and radiation) target the tumor cells directly or indirectly, while immunotherapy attempts to enhance host anti-tumor response. In a manner similar to surgery, photodynamic therapy (PDT), also a local tumor therapy, aims at tumor ablation in its initial acute phase. Treatment success is mainly determined by tumor eradication and the absence of local recurrences. However, experience gained over several decades of therapeutic application has repeatedly hinted at long term therapeutic effects of PDT, suggesting activation of the immune system by this treatment modality. Such contribution of the immune system to treatment success was widely confirmed in many laboratories in various preclinical and some clinical studies. In this present short review, we wish to present our modest contribution to this potential therapeutic trend describing the immune response upon application of a novel photosensitizing methodology: vascular targeted photodynamic therapy (VTP) developed in our laboratories. This modality differs from classical PDT in most aspects (sensitizer: Pd-bacteriochlorophyll and consequent spectral wavelength in the near infrared, the generated photochemistry, the treatment target, treatment objective, treatment protocol and more). For example in contrast to the tumor cells that constitute the target of classical PDT, the targets of VTP are the tumor-feeding arteries and draining veins whose almost instant occlusion (minutes) leads to tumor blood stasis and eradication. Some of the mechanistic features of the induced immune response, such as innate and acquired cellular and humoral mediators, induction of new antigens, resulting from oxidative modifications and implications for anti-tumor vaccination in this different treatment environment, are discussed. VTP is about to enter phase III clinical trials for the therapy of prostate cancer and the potential involvement of the immune system may contribute an interesting aspect for the understanding and future development of this treatment modality.

Focal treatment of prostate cancer with vascular-targeted photodynamic therapy

Focal treatment of prostate cancer with vascular-targeted photodynamic therapy

Minimally invasive ablative therapies for definitive treatment of localized prostate cancer in the primary setting.

Traditionally, the patient with a new diagnosis of localized prostate cancer faces either radical therapy, in the form of surgery or radiation, or active surveillance. A growing subset of these men may not be willing to accept the psychological burden of active surveillance nor the side effects of extirpative or radiation therapy. Local ablative therapies including cryotherapy, high-intensity focused ultrasound, and vascular-targeted photodynamic therapy have emerged as a means for minimally invasive definitive treatment. These treatments are well tolerated with decreased morbidity in association with improvements in technology; however, long-term oncologic efficacy remains to be determined.

Light Density Index (LDI) is a Predictor of MRI and Biopsy Outcome for WST-11 (Tookad Soluble™) Mediated Vascular Targeted Photodynamic Therapy (VTP) in Focal Treatment of Localised Prostate Cancer

Light Density Index (LDI) is a Predictor of MRI and Biopsy Outcome for WST-11 (Tookad Soluble™) Mediated Vascular Targeted Photodynamic Therapy (VTP) in Focal Treatment of Localised Prostate Cancer

Development of an ErbB‐overexpressing A‐431 Optical Reporting Tumor Xenograft Model to Assess Targeted Photodynamic Therapy Regimens

To better assess the efficacy of erbB-targeted therapies, it would help to have optical reporting human tumor xenograft models that abundantly express erbB receptors. A-431 cells have frequently been used in erbB1-targeting studies, but a well-characterized optical reporting version of the cell line has not been readily available. In this study, optical reporting A-431 clones were developed that express both a fluorescent protein reporter (green, GFP; or red, RFP) and a bioluminescent reporter, firefly luciferase. Reporter genes were transduced into cells using commercial lentiviral vectors, and clonal selection was carried out using a series of procedures. A number of clones were isolated for further characterization. A GFP/luciferase clone, A-431/D4, and an RFP/luciferase clone, A-431/G4, were obtained that exhibit erbB1 expression levels and tumor growth kinetics similar to the parental cells. To demonstrate the utility of the optical reporting clones, A-431/G4 tumors were grown subcutaneously in nude mice and treated with vascular-targeted photodynamic therapy (PDT), which targets the angiogenic consequences of erbB signaling. The A-431/G4 tumor model permitted highly sensitive longitudinal monitoring of PDT treatment response using optical imaging. A-431/D4 and A-431/G4 optical reporting tumor models should also prove useful for assessing therapies that directly target the erbB1 receptor.

Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad

BackgroundAntiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP) promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA) and draining veins (DV), leading to tumor necrosis and eradication within 24–48 h.Methodology/Principal FindingsA mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec±1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP.Conclusion/SignificanceTookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.

Neuropilin-1 Targeting Photosensitization-Induced Early Stages of Thrombosis via Tissue Factor Release

This article characterizes the vascular effects following vascular-targeted photodynamic therapy with a photosensitizer which actively targets endothelial cells. This strategy was considered by coupling a chlorin to a heptapeptide targeting neuropilin-1 in human malignant glioma-bearing nude mice. A laser Doppler microvascular perfusion monitor was used to monitor microvascular blood perfusion in tumor tissue. Endothelial cells' ultra structural integrity was observed by transmission electron microscopy. The consequences of photosensitization on tumor vessels, tissue factor expression, fibrinogen consumption, and thrombogenic effects were studied by immunohistochemical staining. Treatment of glioma-bearing mice with the conjugate showed a statistically significant tumor growth delay. Vascular effect was characterized by a decrease in tumor tissue blood flow at about 50% baseline during treatment not related to variations in temperature. This vascular shutdown was mediated by tumor blood vessels' congestion. A pro-thrombotic behavior of targeted endothelial cells in the absence of ultra structural changes led to the induction of tissue factor expression from the earliest times post-treatment. Expression of tissue factor-initiated thrombi formation was also related to an increase in fibrinogen consumption. Using a peptide-conjugated photosensitizer targeting neuropilin-1, induction of tissue factor expression immediately post-treatment, led to the establishment of thrombogenic effects within the vessel lumen.

Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment

Background:Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF2-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.Methods:A multi-modality imaging approach was employed to assess efficacy of treatment, as well as probe the mechanism of action of ADPM06-mediated PDT.Results:Tumour ablation in 71% of animals bearing mammary tumours was achieved after delivery of 2 mg kg−1 of ADPM06 followed immediately by light irradiation with 150 J cm−2. The inherent fluorescence of ADPM06 was utilised to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomography and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumour vascular perfusion and concomitant reduction in tumour metabolism over time after treatment.Conclusion:The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitiser.