Generally speaking, photodynamic therapy (PDT) for cancer has been viewed primarily as a therapeutic approach. In recent years, the integration of photodynamic therapy with secondary treatments has led to a deeper understanding of the sub-therapeutic photodynamic priming effects of PDT. In this work we show that stromal modulation by photodynamic priming of orthotopic head and neck tumors improved the tumor delivery and diagnostic accuracy of the clinical fluorescence image-guided surgery (IGS) probe Cetuximab-IRDye800CW (Cet-IRDye800) by 264.2%. We also explore the role of photodynamic priming in alleviating desmoplasia by reducing the density (>90%) and alignment (>10^3-fold) of collagen fibrillar networks in pancreatic tumors. In doing so, photodynamic priming using EGRF targeted multi-inhibitor liposomes containing irinotecan induced 90% tumor growth inhibition at only 8.1% of the patient equivalent dose of irinotecan, and double overall survival.

Administration of 5-aminolevulinic acid (ALA) as a precursor for protoporphyrin IX (PpIX) is an established photosensitization strategy for photodynamic therapy (PDT) and fluorescence guided surgery. Ongoing studies seek to identify strategies to enhance PpIX accumulation as well as phenotypic traits that correlate with high PpIX conversion. Here we examine PpIX accumulation, PDT response, and differential gene expression in pancreatic and oral cancer cells compared to derivative sublines with acquired drug resistance. The latter exhibit poor differentiation and increased EMT but marked increase in PpIX conversion and enhanced response to PDT. RNAseq analysis shows dramatic changes in expression of genes relevant to PpIX transport (ABCG2) and PpIX formation (ALAD).

We demonstrate a high throughput spectrometer system for real-time measurement of singlet oxygen (1O2) luminescence during photodynamic therapy (PDT). High signal-to-noise spectroscopic data allows for more accurate determination of photosensitizer luminescence baseline via spectral fitting and thus the extraction of 1O2 phosphorescence signal based solely on spectroscopic decomposition, without the need for temporal gating. This enables direct 1O2 measurement in continuous-wave mode, enabling potential clinical use of the technology as a PDT dosimeter. We present results from both in-vitro phantom and in-vivo murine actinic keratosis lesion clearance studies that investigated the correlation of treatment effect with 1O2 measurements during PDT.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.

New technologies for oral cancer detection and timely treatment at the point of care are urgently needed in resource limited clinics in South Asia, which face some of the highest incidence and mortality rates for oral malignancy in the world. Building on previous success with a fiber-coupled intraoral PDT light delivery system we investigate here the implementation of an intraoral diagnostic fluorescence imaging tool for guidance and monitoring PDT response. Our results indicate the utility of this approach while also laying the groundwork for combining cancer screening and treatment with the same hardware going forward.

Two different treatment modalities for skin cancer, topical 5-fluorouracil (5FU) and photodynamic therapy (PDT), have several non-overlapping mechanisms of action in addition to inducing long-term anti-tumor immunity mediated by cells of innate and adaptive immune systems. The particular type of PDT (painless, or p-PDT) uses aminolevulinic acid (ALA) and exposure to blue light in a non-apoptotic regimen resulting in lesion clearance mainly by immunological cell death. When combined, 5FU and p-PDT augment each other in multiple ways, including augmentation of anti-tumor immune activation, resulting in greater tumor reduction than possible with either modality alone.

Contrast-enhanced fluorescent imaging has the potential to improve patient outcomes. A critical challenge that has not been rigorously evaluated is the potential photocytoxicity of the fluorophores used for imaging procedures. In this study, we have used a modified 3T3 Neutral Red Uptake assessment strategy to evaluate 4 imaging dyes and 2 known photosensitizers generating reactive molecular species. Results shed light on the relative photocytotoxicity of tested agents and provide strong evidence on the effectiveness of the method. These methods will provide a foundation for standardizing photo-safety testing of clinical fluorescence imaging products.

Skin-based photodynamic therapy (PDT) is used for the clinical treatment of actinic keratosis (AKs) and other skin lesions with continued expansion into the standard of care. Due to the spectral dependency of photosensitizer activation and skin optical fluence, there is a need for more accurate methods to estimate the delivered dose at depth from different PDT light sources and treatment regimens. Here, we present radiometric methods for calculating photosensitizer-effective fluence and dose at depth and determine differences between red-lamp, blue-lamp, and daylight-based PDT treatments.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.

Photodynamic therapy with aminolevulinic acid and blue light is used in Europe for basal cell carcinoma (BCC), but not in the United States due to uncertainties about efficacy. To potentially improve treatment outcomes and make PDT a more attractive as therapy for BCC, we conducted a prospective, double-blind, crossover clinical trial to test whether pretreatment with oral Vitamin D may enhance BCC responses to blue light PDT. Three separate PDT sessions were administered, with patients receiving daily doses of Vitamin D (10,000 units) or placebo for a week prior to PDT. We will report here on interim clinical trial outcomes.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS 2023.

This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.