Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model

Object Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of resection, indicating that a more aggressive local therapy could be beneficial. Photodynamic therapy (PDT) is a local treatment involving the administration of a tumor-localizing photosensitizing drug, in this case aminolevulinic acid (ALA). The effect depends on the total light energy delivered to the target tissue, but may also be influenced by the rate of light delivery. Methods In vitro experiments showed that the sensitivity to ALA PDT of BT4C multicellular tumor spheroids depended on the rate of light delivery (fluence rate). The BT4C tumors were established intracranially in BD-IX rats. Microfluorometry of frozen tissue sections showed that photosensitization is produced with better than 200:1 tumor/normal tissue selectivity after ALA injection. Four hours after intraperitoneal ALA injection (125 mg/kg), 26 J of 632 nm light was delivered interstitially over 15 (high fluence rate) or 90 (low fluence rate) minutes. Histological examination of animals treated 14 days after tumor induction demonstrated extensive tumor necrosis after low-fluence-rate PDT, but hardly any necrosis after high-fluence-rate treatment. Neutrophil infiltration in tumor tissue was increased by PDT, but was similar for both treatment regimens. Low-fluence-rate PDT administered 9 days after tumor induction resulted in statistically significant prolongation of survival for treated rats compared with nontreated control animals. Conclusions Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the survival for tumor-bearing animals.

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The effect of fluence rate on the acute response of vessel diameter and red blood cell velocity during topical 5-aminolevulinic acid photodynamic therapy

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2014.03.012 ◽

2014 ◽

Vol 11 (2) ◽

pp. 71-81 ◽

Cited By ~ 9

Author(s):

F. van Leeuwen-van Zaane ◽

H.S. de Bruijn ◽

A. van der Ploeg-van den Heuvel ◽

H.J.M.C. Sterenborg ◽

D.J. Robinson

Keyword(s):

Photodynamic Therapy ◽

Blood Cell ◽

Red Blood Cell ◽

Aminolevulinic Acid ◽

Vessel Diameter ◽

Fluence Rate ◽

Acute Response ◽

Cell Velocity ◽

Red Blood Cell Velocity

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Fluence rate variability among light delivery devices for esophageal photodynamic therapy

10.1117/12.699541 ◽

2007 ◽

Author(s):

Jarod C. Finlay ◽

Gregory G. Ginsberg ◽

Stephen M. Hahn

Keyword(s):

Photodynamic Therapy ◽

Fluence Rate ◽

Light Delivery

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A New Light Delivery System for Photodynamic Therapy with Aminolevulinic Acid (ALA) for Treatment of High-Grade Dysplasia in Barrett's Esophagus

Gastrointestinal Endoscopy ◽

10.1016/s0016-5107(05)01266-6 ◽

2005 ◽

Vol 61 (5) ◽

pp. AB233

Author(s):

Mari Ikeguchi ◽

Charles J. Lightdale ◽

Yujeong A. Choi ◽

Kevin Bukowski

Keyword(s):

Photodynamic Therapy ◽

Barrett’S Esophagus ◽

Delivery System ◽

Barrett's Esophagus ◽

Aminolevulinic Acid ◽

High Grade Dysplasia ◽

High Grade ◽

Light Delivery

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Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy

Cancers ◽

10.3390/cancers12061584 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1584 ◽

Cited By ~ 2

Author(s):

Yi Hong Ong ◽

Joann Miller ◽

Min Yuan ◽

Malavika Chandra ◽

Mirna El Khatib ◽

...

Keyword(s):

Blood Flow ◽

Photodynamic Therapy ◽

Treatment Time ◽

High Irradiance ◽

Tumor Oxygenation ◽

Fluence Rate ◽

Tumor Perfusion ◽

Tumor Blood Flow ◽

Light Delivery ◽

Better Than

Fluence rate is an effector of photodynamic therapy (PDT) outcome. Lower light fluence rates can conserve tumor perfusion during some illumination protocols for PDT, but then treatment times are proportionally longer to deliver equivalent fluence. Likewise, higher fluence rates can shorten treatment time but may compromise treatment efficacy by inducing blood flow stasis during illumination. We developed blood-flow-informed PDT (BFI-PDT) to balance these effects. BFI-PDT uses real-time noninvasive monitoring of tumor blood flow to inform selection of irradiance, i.e., incident fluence rate, on the treated surface. BFI-PDT thus aims to conserve tumor perfusion during PDT while minimizing treatment time. Pre-clinical studies in murine tumors of radiation-induced fibrosarcoma (RIF) and a mesothelioma cell line (AB12) show that BFI-PDT preserves tumor blood flow during illumination better than standard PDT with continuous light delivery at high irradiance. Compared to standard high irradiance PDT, BFI-PDT maintains better tumor oxygenation during illumination and increases direct tumor cell kill in a manner consistent with known oxygen dependencies in PDT-mediated cytotoxicity. BFI-PDT promotes vascular shutdown after PDT, thereby depriving remaining tumor cells of oxygen and nutrients. Collectively, these benefits of BFI-PDT produce a significantly better therapeutic outcome than standard high irradiance PDT. Moreover, BFI-PDT requires ~40% less time on average to achieve outcomes that are modestly better than those with standard low irradiance treatment. This contribution introduces BFI-PDT as a platform for personalized light delivery in PDT, documents the design of a clinically-relevant instrument, and establishes the benefits of BFI-PDT with respect to treatment outcome and duration.

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Optimization of brain photodynamic therapy : a study of extended-time low-fluence-rate ALA-photodynamic therapy in a rat glioma mode

10.32920/ryerson.14646606 ◽

2021 ◽

Author(s):

Hadi Karimi

Keyword(s):

Photodynamic Therapy ◽

Tumor Cells ◽

Alternative Treatment ◽

Tumor Recurrence ◽

Tumor Control ◽

Fluence Rate ◽

Extended Time ◽

Brain Glioma ◽

Rat Glioma ◽

Light Delivery

The importance of the rate of light delivery and the length of photodynamic therapy as an alternative treatment modality for brain glioma have been investigated and shown that optimized PDT regimens would have the potential to reduce the tumor recurrence and the treatment-induced morbidity. In a rat glioma model, using photosensitizer ALA-PpIX, we further investigated the effect of extended-time low-fluence-rate PDT on the number of apoptotic, necrotic, surviving, and infiltrated tumor cells, associated with three fluence rates of 0.5, 1.0, and 1.5 mW cm⁻², each at three treatment lengths of 24, 48, and 72 hours. Our results demonstrated that lowest fluence rate used in our study has an improved apoptosis to necrosis ratio; however higher fluence rates show a clear supremacy for tumor control in shorter treatment times. Therefore, low-fluence-rate brain ALA-PDT may only be more beneficial for tumor control at longer treatment periods.

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Photodynamic Therapy in Refractory Mycosis Fungoides: A Prospective, Open-Label Study

Blood ◽

10.1182/blood-2020-141119 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Caitlin M Brumfiel ◽

Kevin J Severson ◽

Meera H Patel ◽

Helen J L Cumsky ◽

Brenda F Ginos ◽

...

Keyword(s):

Photodynamic Therapy ◽

Mycosis Fungoides ◽

Blue Light ◽

Ad Hoc ◽

Aminolevulinic Acid ◽

Objective Response ◽

Response Rates ◽

Physician Global Assessment ◽

Target Tissue ◽

Open Label

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.

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Photoprotective Effect of the PlantCollaea argentinaagainst Adverse Effects Induced by Photodynamic Therapy

International Journal of Photoenergy ◽

10.1155/2014/436463 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8

Author(s):

Leandro Mamone ◽

Daniel Sáenz ◽

Pablo Vallecorsa ◽

Alcira Batlle ◽

Adriana Casas ◽

...

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Methanolic Extract ◽

Target Tissue ◽

Adenocarcinoma Cell Line ◽

Extract Concentration ◽

Promising Agent ◽

Main Disadvantage ◽

Long Time ◽

Cutaneous Damage

Photodynamic therapy (PDT) is a treatment modality for tumours and other accessible lesions based on the combination of light and a photosensitizer (PS) accumulated in the target tissue. The main disadvantage of PDT is PS retention after treatment during long time periods that conduces to cutaneous damage. It is believed that singlet oxygen is responsible for that skin photosensitization. The aim of this work was to evaluate the photoprotective activity of the methanolic extract of the Argentinian plantCollaea argentinaagainst PDT under several treatments and employing different PSs.C. argentinaexhibited photoprotective activity against aminolevulinic acid- (ALA-) PDT in the LM2 murine adenocarcinoma cell line. The photoprotection was dependant on the extract concentration and the incubation time, being detectable from 40 μg/mL onwards and at least after 3 h exposure of the cells.C. argentinaextract protects these mammalian tumor cells against PDT effects, and it interferes with the oxygen singlet production from PSs during PDT treatment. We propose that it will be a promising agent to protect cells against PDT-induced skin sensitivity.

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