Ron R. Allison

Photosensitizers in clinical PDT

Photosensitizers in photodynamic therapy allow for the transfer and translation of light energy into a type II chemical reaction. In clinical practice, photosensitizers arise from three families-porphyrins, chlorophylls, and dyes. All clinically successful photosensitizers have the ability to a greater or lesser degree, to target specific tissues or their vasculature to achieve ablation. Each photosensitizer needs to reliably activate at a high enough light wavelength useful for therapy. Their ability to fluoresce and visualize the lesion is a bonus. Photosensitizers developed from each family have unique properties that have so far been minimally clinically exploited. This review looks at the potential benefits and consequences of each major photosensitizer that has been tried in a clinical setting.

Oncologic photodynamic therapy photosensitizers: a clinical review.

A myriad of naturally occurring and synthetic structures are capable of transferring the energy of light. Few, however, allow for this energy transfer to enable a type II photochemical reaction which, as currently practiced, is a fundamental component of photodynamic therapy. Even fewer of these agents, aptly termed photosensitizers, have found success in the treatment of patients. This review will focus on the oncologic photosensitizers that have come to clinical trial with outcomes published in peer reviewed journals. Based on a clinical orientation the qualities of successful photosensitizers will be examined, how current drugs fare and potential future options explored.

Photodynamic Therapy (PDT): PDT Mechanisms

Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients.

Bio-nanotechnology and photodynamic therapy—State of the art review

Photodynamic therapy (PDT) and bio-nanotechnology (NT) show striking similarities in clinical design and mechanistics. The PDT paradigm of photosensitizer application, light activation and singlet oxygen generation does in fact occur on the nanoscale level as does the resultant outcomes. NT has the ability to explain as well as modify each of the critical steps of PDT particularly photosensitizer design and delivery, light source miniaturization and optimization, location and intensity of the photodynamic reaction as well as offering a far greater insight into dosimetry and mechanisms of action. This review will explore the current and potential future interactions and modifications NT may have on PDT.

Clinical PD/PDT in North America: An historical review

The healing properties of light have been appreciated for thousands of years. However, the harnessing of light energy to create a rigorous and reliable means to diagnose and treat human disease is only a relatively recent phenomenon. Despite outstanding results from ancient history and subsequent reemergence and refinement of this knowledge over the last 100 years, it took again the hand of serendipity to open the modern age of Photodiagnosis and Photodynamic Therapy. Based on the prescience and perseverance of a handful, the under appreciated observations of tumor fluorescence and photodynamic action have been brought to a worldwide audience. This review highlights the development of clinical Photodiagnosis and Photodynamic Therapy, emphasizing the significant events and milestones taking place in North America.

Breast Cancer With Chest Wall Progression: Treatment With Photodynamic Therapy

Background: Chest wall progression of breast carcinoma affects up to 5% of breast cancer patients and is a major source of their pain. Treatment options are limited or may not be offered to these patients. Low-dose Photofrin-induced photodynamic therapy (PDT) offers an excellent clinical response with minimal morbidity. We report our continued experience with PDT in this setting.Methods: Fourteen patients with more than 500 truncal metastases were treated with PDT. All received off-label Photofrin (.8 mg/kg) IV and light treatment at 630 nm from a diode laser with a microlens at a fluence of 1800 mW and a total light dose of 150 to 200 J/cm2 at 48 hours. One patient required re-treatment because of extensive disease.Results: Follow-up was at least 6 months, and several extended to >24 months. All patients demonstrated tumor necrosis, with 9 of 14 complete responses, including with lesions >2 cm in thickness. Disease progression occurred outside of the treatment field. Several patients had initial regression of untreated lesions. Wound care, especially with disease in the deep tissues, was an issue.Conclusions: Low-dose Photofrin-induced PDT offers patients with chest wall progression a treatment option with an excellent clinical response. To date, the response is prolonged and offers good local control. Surgical oncologists have an active role in this treatment option.

The future of photodynamic therapy in oncology.

The medicinal properties of light-based therapies have been appreciated for millennia. Yet, only in this century have we witnessed the birth of photodynamic therapy (PDT), which over the last few decades has emerged to prominence based on its promising results and clinical simplicity. The fundamental and distinguishing characteristics of PDT are based on the interaction of a photosensitizing agent, which, when activated by light, transfers its energy into an oxygen-dependent reaction. Clinically, this photodynamic reaction is cytotoxic and vasculotoxic. While the current age of PDT is based on oncological therapy, the future of PDT will probably show a significant expansion to non-oncological indications. This harks back to much of the original work from a century ago. Therefore, this paper will attempt to predict the future of PDT, based in part on a review of its origin.

Identification of extracellular δ-catenin accumulation for prostate cancer detection

Prostate cancer is the second leading cause of cancer death in men, and early detection is essential to reduce mortality and increase survival. δ‐Catenin is a unique β‐catenin superfamily protein primarily expressed in the brain but is upregulated in human prostatic adenocarcinomas. Despite its close correlation with the disease, it is unclear whether δ‐catenin presents the potential in prostate cancer screening because it is an intracellular protein. In this study, we investigated the hypothesis of δ‐catenin accumulation in the urine of prostate cancer patients and its potential pathways of excretion into extracellular milieu.

Future of oncologic photodynamic therapy

Photodynamic therapy (PDT) is a tumor-ablative and function-sparing oncologic intervention. The relative simplicity of photosensitizer application followed by light activation resulting in the cytotoxic and vasculartoxic photodynamic reaction has allowed PDT to reach a worldwide audience. With several commercially available photosensitizing agents now on the market, numerous well designed clinical trials have demonstrated the efficacy of PDT on various cutaneous and deep tissue tumors. However, current photosensitizers and light sources still have a number of limitations. Future PDT will build on those findings to allow development and refinement of more optimal therapeutic agents and illumination devices. This article reviews the current state of the art and limitations of PDT, and highlight the progress being made towards the future of oncologic PDT.

Oncologic photodynamic therapy: clinical strategies that modulate mechanisms of action.

Photodynamic therapy (PDT) is an elegant minimally invasive oncologic therapy. The clinical simplicity of photosensitizer (PS) drug application followed by appropriate illumination of target leading to the oxygen dependent tumor ablative Photodynamic Reaction (PDR) has gained this treatment worldwide acceptance. Yet the true potential of clinical PDT has not yet been achieved. This paper will review current mechanisms of action and treatment paradigms with critical commentary on means to potentially improve outcome using readily available clinical tools.