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Tehran University of Medical Sciences

2021

Dr. Marjaneh Hejazi

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photodynamic therapy laser therapy biomedical physics medical physics

Summary

This document is a presentation on Photodynamic Therapy (PDT). It covers the necessity of radiation dosimetry in PDT, the applications of lasers, and the introduction of medical physicists in therapeutic departments. The presentation also includes references to relevant research articles.

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Duration: 120 min Second session Photodynamic Therapy Presented by :Dr.Marjaneh Hejazi 12/13/2021 ١ Learning objectives Keywords...

Duration: 120 min Second session Photodynamic Therapy Presented by :Dr.Marjaneh Hejazi 12/13/2021 ١ Learning objectives Keywords the necessity of radiation dosimetry and eventually Photodynamic therapy,physics, dosimetry treatment planning in the biomedical.applications of lasers Introduction of Medical Physicists in the therapeutic departments in the hospital Recommended article for your lecture References Zhu, T.C. and Finlay, J.C., 2008. The role of photodynamic therapy (PDT) physics. Medical Combination of Photodynamic Therapy with Radiotherapy for.physics, 35(7Part1), pp.3127-3136 Cancer Treatment Jing Xu,1 Jianqing Gao,2 and Qichun Wei Kim, M.M. and Darafsheh, A., 2020. Light sources and dosimetry techniques for.photodynamic therapy. Photochemistry and photobiology, 96(2), pp.280-294 Makropoulou, M., Kareliotis, G., Spyratou, E., Drakaki, E., Serafetinides, A.A. and Efstathopoulos, E., 2019. Non-ionizing, laser radiation in Theranostics: The need for.dosimetry and the role of Medical Physics. Physica Medica, 63, pp.7-18 12/13/2021 ٢ Today ‘s Content Some introductory remarks Laser radiation: definition, properties, and biomedical applications Laser – Tissue interactions and photobiological mechanisms Biomedical laser applications in phototherapy Current areas of basic PDT research PDT Dosimetry PDT future research Summary 12/13/2021 ٣ PDT 1.Some introductory remarks 21th years 60 Centur After y 21th Century Laser discovery 1960 12/13/2021 ٤ PDT 2. Laser radiation: definition, properties, and biomedical applications EXCIMER 12/13/2021 ٥ PDT 2. Laser radiation: definition, properties, and biomedical applications 12/13/2021 ٦ PDT 2. Laser radiation: definition, properties, and biomedical applications all light-based technologies applied to life sciences and medicine form an emerging multidisciplinary research area, named Biophotonics Biophotonics is the combination of the Greek syllables “bios” standing for life and “phos” standing for light 12/13/2021 ٧ PDT Laser radiation: definition, properties,.2 and biomedical applications The link between thera(peutics) and diag(nostics) led to the development of a new field, entitled “Theranostics” thera(peutics) diag(nostic) 12/13/2021 ٨ PDT Laser radiation: definition, properties,.2 and biomedical applications 12/13/2021 ٩ PDT 2. Laser radiation: definition, properties, and biomedical applications 12/13/2021 ١٠ PDT Laser radiation: definition, properties,.2 and biomedical applications 12/13/2021 ١١ PDT 2. Laser radiation: definition, properties, and biomedical applications As a consequence, safety for patients and health care personnel depends on the safe and effective use/supervision of lasers by a qualified expert, the Laser Safety Officer (LSO) or Medical Laser Safety Officer (MLSO). The LSO/MLSO, who is responsible for directing the safe use of lasers and ensuring compliance with laser hazard standards and controls, could also have a Medical Physicist’s license. In this optimal case, he/she would have not only the necessary knowledge of laser safety but also of important medical physics aspects 12/13/2021 ١٢ PDT Laser – Tissue interactions and.3 photobiological mechanisms 12/13/2021 ١٣ PDT 3. Laser – Tissue interactions and photobiological mechanisms 3.1. Photochemical effects Photochemical processes result from molecular photo-excitation, following absorption of one or more photons. c From there a variety of chemical reactions are possible, such as the generation of free radicals and reactive oxygen species (ROS). 12/13/2021 ١٤ PDT 4. Biomedical laser applications and the involvement of dosimetry The main applications, based on photochemical mechanism of laser- tissue interaction, are c Photodynamic therapy (PDT) of tumors, Biostimulation for wound healing in the so called low level laser therapy (LLLT), Photochemcial ablation and photodistruption. 12/13/2021 ١٥ PDT Definition 4.Biomedical laser applications in phototherapy and the involvement of dosimetry Photodynamic therapy (PDT) is a light-activated chemotherapy in which light is sused to activate a c photosensitive drug that has accumulated within cells such that it causes oxidative injury to the cell 12/13/2021 ١٦ Definition PDT 4.Biomedical laser applications in phototherapy and the involvement of dosimetry PDT is a non-invasive technique, based on the simultaneous action of the following three factors i) photosensitizing agent (PS), able to photochemically eradicate malignant cs cells, ii) molecular oxygen (3O2), generating highly reactive singlet oxygen iii) non-thermal monochromatic light irradiation. 12/13/2021 ١٧ PDT 4.Biomedical laser applications in phototherapy and the involvement of dosimetry PDT is a non-invasive technique, based on the simultaneous action of the following three factors i) photosensitizing agent (PS), able to photochemically eradicate malignant cs cells, ii) molecular oxygen (3O2), generating highly reactive singlet oxygen iii) non-thermal monochromatic light irradiation. 12/13/2021 ١٨ Type II mechanism PDT 4.Biomedical laser applications in phototherapy and the involvement of dosimetry sc 12/13/2021 ١٩ Triplet oxygen is the ground state of the oxygen molecule. The electron configuration of the molecule has two unpaired electrons occupying two degenerate.molecular orbitals 12/13/2021 ٢٠ 12/13/2021 ٢١ Type II mechanism PDT 4.Biomedical laser applications in phototherapy and the involvement of dosimetry sc 12/13/2021 ٢٢ Light source, transport, and PDT 5.Current areas of basic PDT delivery research and the involvement of dosimetry These requirements impose the use of photons in the 600–850 nm region of the electromagnetic spectrum, since at wavelengths higher than 850–900 nm the photons might c not have sufficient energy to produce 1O2. On the contrary, the most energetic photons in UV – VIS region of the spectrum have lower penetration depth 12/13/2021 ٢٣ :Light source PDT 5.Current areas of basic PDT research Lasers,LED, Delivery device Lasers and the involvement of dosimetry Diode lasers are fixed in wavelength and therefore a separate laser unit is needed for each photosensitizer that absorbs at a unique wavelength of excitation. c Clinical diode lasers can provide irradiance up to 1 W cm-2. Diode lasers with output wavelengths in 415–690 nm range are typically used in PDT 12/13/2021https://www.youtube.com/ ٢٤ watch?v=0DCrIAxEv_Y :Light source :Light source PDT 5.Current areas of basic PDT research Lasers,LED,Lamps Lasers,LED, Delivery devices Lasers and the involvement of dosimetry sc 12/13/2021https://www.youtube.com/ ٢٥ watch?v=0DCrIAxEv_Y 5.Current areas of basic PDT :Light source PDT Lasers,LED, Delivery device research and the involvement of LEDs dosimetry sc 12/13/2021https://www.youtube.com/ ٢٦ watch?v=0DCrIAxEv_Y :Light source PDT 5.Current areas of basic PDT research and Lasers,LED,Delivery device LEDs the involvement of dosimetry sc 12/13/2021https://www.youtube.com/ ٢٧ watch?v=0DCrIAxEv_Y :Light source PDT Current areas of basic PDT research and the Lasers,LED, Delivery device Delivery devices involvement of dosimetry sc 12/13/2021https://www.youtube.com/ ٢٨ watch?v=0DCrIAxEv_Y Near Infra red NIR 12/13/2021 ٢٩ :Light source PDT 5.Current areas of basic PDT research and Lasers,LED, Delivery device Delivery devices the involvement of dosimetry Based on the light delivery technique, PDT light delivery devices can be classified as Non-contact,s c Contact, Interstitial 12/13/2021https://www.youtube.com/ ٣٠ watch?v=0DCrIAxEv_Y :Light source PDT 5.Current areas of basic PDT research and the Lasers,LED, Delivery device Delivery devices involvement of dosimetry Modes are well-defined spatial profiles of electromagnetic fields that are repeated at equal intervals along the fiber. Only a certain discrete number of modes (certain ray directions) can be guided in the fiber, based s on that c fibers are classified as Single-mode Multimode. 12/13/2021https://www.youtube.com/ ٣١ watch?v=0DCrIAxEv_Y Current areas of basic PDT :Light source PDT Lasers,LED, Delivery device Delivery devices research sc 12/13/2021https://www.youtube.com/ ٣٢ watch?v=0DCrIAxEv_Y PDT 5.Current areas of basic PDT research Dosimetry and the involvement of dosimetry Three different dosimetric methodologies can be used for PDT dosimetry: Implicit dosimetry, Explicit dosimetry, s c Direct dosimetry ٣٣ Dosimetry ,Explicit dosimetry PDT 5.Current areas of basic PDT research and the involvement of dosimetry The first option is to measure each parameter directly and independently (including measurements during treatment) and to build a s resultant dose metric by combining these, using c some model of how the photodynamic response depends on the variables. This will be referred to here as 'explicit dosimetry', since each dose variable is measured explicitly. ٣٤ Dosimetry ,Implicit dosimetry PDT 5.Current areas of basic PDT research and the involvement of dosimetry 'implicit dosimetry', is to use a metric (eg photobleaching) which implicitly incorporates some, or preferably all, of the dose parameters, while not necessarily measuring any of them directly. c ٣٥ C=Direct a=explicit b) implicit 12/13/2021 ٣٦ PDT Dosimetry Current areas of basic PDT.5 research and the involvement of dosimetry sc 12/13/2021https://www.youtube.com/ ٣٧ watch?v=0DCrIAxEv_Y PDT Current areas of basic PDT.5 Dosimetry pleural photodynamic research and the involvement of therapy dosimetry Pleural PDT is performed intraoperatively for the treatment of microscopic diseases in patients with malignant pleural mesothelioma. Patients received sc the PS Photofrin at 2 mg per kg body weight 24 hours prior to surgery Laser diode at wavelength of 630 nm was used. Power desnity was 60 J/cm2 Measured by 8 isotropic detectors sutured on apex posterior chest wall, anterior chest wall ٣٨ PDT 5.Current areas of basic PDT Dosimetry pleural research and the involvement of photodynamic therapy dosimetry A commercial IR navigation system was used for tracking the light delivery during pleura PDT c 12/13/2021https://www.youtube.com/ ٣٩ watch?v=0DCrIAxEv_Y Beam Profiler FWHM 12/13/2021 ٤٠ PDT 5.Current areas of basic PDT Dosimetry pleural photodynamic research and the involvement of therapy dosimetry sc 12/13/2021https://www.youtube.com/ ٤١ watch?v=0DCrIAxEv_Y PDT 6.PDT future research and the Applications involvement of dosimetry Studies have shown some efficacy in the treatment of a variety of malignant and premalignant conditions including sc head and neck cancer, lung cancer, mesothelioma, Barrett’s esophagus, prostate brain tumors. 12/13/2021 ٤٢ PDT PDT future research and the Applications involvement of dosimetry Continuing research has also been aimed toward targeted delivery of photosensitizers and drugs with nanotechnology), although still at the proof-of-principle stage. This depends on cs the successful synthesis of nanoparticles with high tumor uptake selectivity 12/13/2021 ٤٣ PDT PDT future steps Applications In order to overcome the shallow light penetration in tissue, several studies suggested combining external beam radiation therapy with PDT. However, due to sthe significant energy mismatch between the therapeutic x-rays and c the photosensitizer, photosensitizers cannot be directly excited by the xrays. Instead, the photosensitizer is activated by using radioluminescence of nanoparticles (scintillation or persistent luminescence) or induced Cerenkov radiation. Scintillating nanoparticles (SCNPs) can promptly down-convert x-ray radiation into visible light through scintillation process and activate the adjacent photosensitizer to initiate PDT 12/13/2021 ٤٤ PDT PDT future steps Applications The typical total energy delivered in a stand-alone PDT treatment is 4–5 orders of magnitude higher than that in a typical course of ionizing radiation therapy. Hence, any strategy cs that relies on ionizing radiation to power PDT, even with complete conversion efficiency, must depend on very low dose rate PDT and synergy with radiation damage Recently, a miniaturized wireless implantable device equipped with two LEDs (red and blue) was proposed for local light delivery and dosimetry ( 12/13/2021 ٤٥ PDT conclusion Second session. Closing this work, a question is naturally formed: What do we expect from the advances in Physics for the field of Medical Physics? In Oncology the efforts in finding and curing cancer impose the bridging of ionizing radiation (where the role of Medical Physics is inevitable) with non-ionizing laser radiation (where the role of Medical Physics is gradually recognized).. This is a paradigm for which a well-trained Medical Physicist in both radiation physics and laser-matter interactions is needed for dosimetry, treatment planning and safety responsibilities. 12/13/2021 ٤٦ PDT Summary safety for patients and health care personnel depends on the safe and effective use/supervision of lasers by a qualified expert, the Laser Safety Officer (LSO) or Medical Laser Safety.Officer (MLSO) The LSO/MLSO, who is responsible for directing the safe use of lasers and ensuring compliance with laser hazard standards 21th Century and controls, could also have a Medical Physicist’s license 12/13/2021 ٤٧ PDT Summary A special demand for better understanding of the basic biophysical mechanisms of light propagation into biological media and the prediction of laser-tissue interactions is of great importance for the optimization of.effective and safe clinical laser applications 21th Century Depending on the end result of photonic ,energy conversion in another energy form :we can differentiate between three major photobiological effects photochemical effects, photothermal effects and photomechanical effects 12/13/2021 ٤٨ PDT Summary Photochemical processes result from molecular photo-excitation,.following absorption of one or more photons The main applications, based on photochemical mechanism of laser-tissue interaction, are photodynamic therapy (PDT) of tumors, biostimulation for wound healing in the so.called low level laser therapy (LLLT), photodiagnosis and photo-detection 21th Century Photodynamic therapy (PDT) is a light-activated chemotherapy in which light is used to activate a photosensitive drug that has accumulated within cells such that it causes oxidative injury to the cell 12/13/2021 ٤٩ PDT Summary 21th Century 12/13/2021 ٥٠ PDT Assignment Second session TOPICAL REVIEW An update on clinical photodynamic therapy for fighting respiratory tract infections: a promising tool against COVID-19 and its co-infections Lucas D Dias1 and Vanderlei S Bagnato1,2 Published 26 June 2020 © 2020 Astro Ltd Laser Physics Letters, Volume 17, Number 8 12/13/2021 ٥١ Thank you for your attention 12/13/2021 ٥٢

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