Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

Maytin, Edward V.; Anand, Sanjay; Baran, Christine B. Warren; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

doi:10.1117/12.808174

Cited by 6 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While fluorescence imaging of PpIX has been proposed as a method to define the borders of skin tumors prior to surgical removal, [16][17][18][19] our findings suggest an additional potential use. Because the conversion of ALA to PpIX reflects changes in metabolic activity within neoplastic cells, 13,20 PpIX fluorescence imaging should be further explored as a technique to identify epidermal regions that harbor precancerous changes that might otherwise go undetected.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

et al. 2010

View full text Add to dashboard Cite

Abstract. Topical 5-aminolevulinic acid ͑ALA͒ is widely used in photodynamic therapy ͑PDT͒ of actinic keratoses ͑AK͒, a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX ͑PpIX͒ accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements ͑5 replicates͒ were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin. © 2010 Society of Photo-Optical Instrumentation Engineers.

show abstract

Section: Discussionmentioning

confidence: 99%

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The PpIX elevating drugs that were identified to date include topical Vitamin D 21 , systemic Vitamin D 22 , and systemic methotrexate 17,19 . A critical aspect here is the fact that all of these agents enhance the selectivity of PDT by preferentially enhancing PpIX accumulation in preneoplastic and neoplastic cells and tissues, while causing very little damage to normal cells 19,20,23 . Not only is the local tumor kill enhanced, but targeting of the tumor tissue becomes more selective, and toxicity to surrounding normal tissue is reduced.…”

Section: Photodynamic Therapy (Pdt) For Skin Cancermentioning

confidence: 99%

“…This principle relies upon the observation that certain pharmacologic agents, for which we have coined the term "differentiating agents," can enhance PpIX accumulation within a variety of epithelial cancer cells [15][16][17][18] and also in benign and malignant skin tumors in mice 19,20 . The PpIX elevating drugs that were identified to date include topical Vitamin D 21 , systemic Vitamin D 22 , and systemic methotrexate 17,19 .…”

Section: Photodynamic Therapy (Pdt) For Skin Cancermentioning

confidence: 99%

5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

et al. 2011

Self Cite

View full text Add to dashboard Cite

was developed in the 1950s as an anticancer drug and is now widely used to treat many cancers, including colon and breast carcinoma. 5-FU causes fluoronucleotide misincorporation into RNA and DNA, inhibits thymidylate synthase, and leads to growth arrest and apoptosis. For skin precancers (actinic keratoses; AK), 5-FU is prescribed as a topical agent and was essentially the only option for treating widespread AK of the skin prior to FDA approval of photodynamic therapy (PDT) in 1999. PDT is now gradually replacing 5-FU as a preferred treatment for AK, but neither PDT nor 5-FU are effective for true skin cancers (basal or squamous cell), particularly for tumors >1 mm in depth. In our ongoing work to improve the efficacy of PDT for skin cancer, we previously showed that PDT efficacy can be significantly enhanced by preconditioning tumors with methotrexate (MTX), which leads to increased production of protoporphyrin IX (PpIX) in target cells. However, because MTX must be given orally or intravenously, it is considered unacceptable for widespread human use due to potential toxicity. MTX and 5-FU exert similar effects on the thymidylate synthesis pathway, so we reasoned that topical 5-FU could be a potential alternative to MTX. In this paper, exploratory studies that test 5-FU as a preconditioning agent for PDT are presented. In a cutaneous model of squamous cell carcinoma (chemically-induced papillomatous tumors in mice), 5-FU significantly enhances PpIX accumulation and therefore emerges as a new candidate agent for combination therapy with PDT.

show abstract

“…For superficial NMSCs, ALA-PDT has efficacy close to surgery with sometimes better cosmetic and functional outcomes. However, the efficacy is limited for thicker and deeper tumors (3–6). Thus, tumor size information can allow for a better PDT planning.…”

mentioning

confidence: 99%

Preoperative Mapping of Nonmelanoma Skin Cancer Using Spatial Frequency Domain and Ultrasound Imaging

et al. 2014

View full text Add to dashboard Cite

Rationale and Objectives The treatment of nonmelanoma skin cancer (NMSC) is usually by surgical excision or Mohs micrographic surgery and alternatively may include photodynamic therapy (PDT). To guide surgery and to optimize PDT, information about the tumor structure, optical parameters, and vasculature is desired. Materials and Methods Spatial frequency domain imaging (SFDI) can map optical absorption, scattering, and fluorescence parameters that can enhance tumor contrast and quantify light and photosensitizer dose. High frequency ultrasound (HFUS) imaging can provide high-resolution tumor structure and depth, which is useful for both surgery and PDT planning. Results Here, we present preliminary results from our recently developed clinical instrument for patients with NMSC. We quantified optical absorption and scattering, blood oxygen saturation (StO2), and total hemoglobin concentration (THC) with SFDI and lesion thickness with ultrasound. These results were compared to histological thickness of excised tumor sections. Conclusions SFDI quantified optical parameters with high precision, and multiwavelength analysis enabled 2D mappings of tissue StO2 and THC. HFUS quantified tumor thickness that correlated well with histology. The results demonstrate the feasibility of the instrument for noninvasive mapping of optical, physiological, and ultrasound contrasts in human skin tumors for surgery guidance and therapy planning.

show abstract

Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

Cited by 6 publications

References 0 publications

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?

Preoperative Mapping of Nonmelanoma Skin Cancer Using Spatial Frequency Domain and Ultrasound Imaging

Contact Info

Product

Resources

About