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

Author(s):  
Hadi Karimi

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.

2021 ◽  
Author(s):  
Hadi Karimi

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.


2007 ◽  
Author(s):  
Jarod C. Finlay ◽  
Gregory G. Ginsberg ◽  
Stephen M. Hahn

2012 ◽  
Vol 10 (Suppl_2) ◽  
pp. S-14-S-17 ◽  
Author(s):  
Gary S. Rogers

A principal factor in determining the biologic consequences of photodynamic therapy (PDT) is the light fluence rate. Preclinical and, more recently, clinical studies have focused on low-irradiance schemes, suggesting that prolonged light exposure, better known as CLIPT (continuous low-irradiance PDT), may improve tumor control while reducing morbidity. After a brief look at the origin of light therapy and photosensitizers, this article turns to the promising animal research supporting the use of low- and ultra-low fluence rate PDT, which serves as the basis of the ongoing CLIPT dosimetry trials for patients with chest wall progression of breast cancer. The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system.


2006 ◽  
Vol 104 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Even Angell-Petersen ◽  
Signe Spetalen ◽  
Steen J. Madsen ◽  
Chung-Ho Sun ◽  
Qian Peng ◽  
...  

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.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1584 ◽  
Author(s):  
Yi Hong Ong ◽  
Joann Miller ◽  
Min Yuan ◽  
Malavika Chandra ◽  
Mirna El Khatib ◽  
...  

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.


2008 ◽  
Vol 14 (9) ◽  
pp. 2796-2805 ◽  
Author(s):  
Mukund Seshadri ◽  
David A. Bellnier ◽  
Lurine A. Vaughan ◽  
Joseph A. Spernyak ◽  
Richard Mazurchuk ◽  
...  

2015 ◽  
Vol 14 (8) ◽  
pp. 1403-1409 ◽  
Author(s):  
Mladen Korbelik ◽  
Michael R. Hamblin

PDT has different effects on macrophages in tumors. The photosensitizer (PS) is taken up by M2 TAMS inside the tumor, which are killed upon light delivery. Signaling from these dying cells attracts new M1 macrophages from the circulation that can kill remaining tumor cells and stimulate an adaptive immune response.


Author(s):  
Patricia S.P. Thong ◽  
Malini Olivo ◽  
Kiang-Wei Kho ◽  
Ramaswamy Bhuvaneswari ◽  
William W. L. Chin ◽  
...  

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.


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