R. Schütz, I. Shchatsinin, U. Bindig, C. Reble, J. Helfmann
Abstract A change in the water distribution of the human body, such as water retention in the skin, can be a symptom of a pathological condition including heart failure. Therefore, a sensor for the non-invasive quantification of the water content of the skin could be useful where continuous monitoring of patients is required to detect and avoid life threatening conditions. As water is a major absorber of tissue in the near-infrared wavelength range, the water content can be determined based on reflectance measurements. Measuring the diffuse reflectance at multiple distances from the point of illumination allows the determination of absorption in scattering media such as skin. The aim of this project was to develop a small and portable sensor based on light emitting diodes and photodiodes. Evaluation of the first functional sensor design has showed that the water content of tissue phantoms can be predicted with a prediction error of 1%. Further developments towards a sensor that can be applied in a future field study are ongoing.
{"title":"Development of an in-vivo sensor for monitoring of water content in skin","authors":"R. Schütz, I. Shchatsinin, U. Bindig, C. Reble, J. Helfmann","doi":"10.1515/plm-2014-0046","DOIUrl":"https://doi.org/10.1515/plm-2014-0046","url":null,"abstract":"Abstract A change in the water distribution of the human body, such as water retention in the skin, can be a symptom of a pathological condition including heart failure. Therefore, a sensor for the non-invasive quantification of the water content of the skin could be useful where continuous monitoring of patients is required to detect and avoid life threatening conditions. As water is a major absorber of tissue in the near-infrared wavelength range, the water content can be determined based on reflectance measurements. Measuring the diffuse reflectance at multiple distances from the point of illumination allows the determination of absorption in scattering media such as skin. The aim of this project was to develop a small and portable sensor based on light emitting diodes and photodiodes. Evaluation of the first functional sensor design has showed that the water content of tissue phantoms can be predicted with a prediction error of 1%. Further developments towards a sensor that can be applied in a future field study are ongoing.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"40 1","pages":"197 - 201"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79386272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background and objective: Thin films of bacteria, proteins and other biochemical substances are always found on surfaces exposed to the environment. Optical methods enable innovative tools for the detection of such films, as residua of proteins and other substances that exhibit fluorescence when excited with UV light. Sensor design: This paper presents and evaluates a specially designed handheld measuring device for this purpose. Results: The sensor is able to detect low concentrations of organic contamination with measurement times shorter than a second. The results presented in this paper show that detection of contamination levels of bovine serum albumin down to 200 ng/cm2 is possible on non-fluorescent substrate materials. Conclusion: Future development of handheld optical devices suitable for the detection or analysis of various compounds could be based on these results.
{"title":"Fluorescence-optical handheld non-contact sensor for rapid cleaning validation of surfaces","authors":"H. Cappius, J. Börner, H. Südmeyer, F. Schmitt","doi":"10.1515/plm-2014-0042","DOIUrl":"https://doi.org/10.1515/plm-2014-0042","url":null,"abstract":"Abstract Background and objective: Thin films of bacteria, proteins and other biochemical substances are always found on surfaces exposed to the environment. Optical methods enable innovative tools for the detection of such films, as residua of proteins and other substances that exhibit fluorescence when excited with UV light. Sensor design: This paper presents and evaluates a specially designed handheld measuring device for this purpose. Results: The sensor is able to detect low concentrations of organic contamination with measurement times shorter than a second. The results presented in this paper show that detection of contamination levels of bovine serum albumin down to 200 ng/cm2 is possible on non-fluorescent substrate materials. Conclusion: Future development of handheld optical devices suitable for the detection or analysis of various compounds could be based on these results.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"4 1","pages":"169 - 175"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80944119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract There is currently no non-invasive measurement method available on the market for the quality control of red cell concentrates (RCCs). As the level of free hemoglobin is an indicator for hemolysis resulting from destroyed or overaged red blood cells, it is an important parameter to assess the quality and usability of RCCs before transfusion. A new optical device has been developed and tested to enable the measurement of the free hemoglobin concentration non-invasively in RCCs.
{"title":"Non-invasive detection of free hemoglobin in red blood cell concentrates for quality assurance","authors":"U. Netz, L. Hirst, M. Friebel","doi":"10.1515/PLM-2014-0054","DOIUrl":"https://doi.org/10.1515/PLM-2014-0054","url":null,"abstract":"Abstract There is currently no non-invasive measurement method available on the market for the quality control of red cell concentrates (RCCs). As the level of free hemoglobin is an indicator for hemolysis resulting from destroyed or overaged red blood cells, it is an important parameter to assess the quality and usability of RCCs before transfusion. A new optical device has been developed and tested to enable the measurement of the free hemoglobin concentration non-invasively in RCCs.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"5 1","pages":"193 - 195"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85687507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As part of the LASER World of PHOTONICS Congress and Exhibition, which will be held from 22 to 25 June 2015 at the International Congress Centre Munich, the Deutsche Gesellschaft für Lasermedizin (DGLM) e.V. is organizing an application panel on the topic “Laser-advanced new methods for diagnostics and therapeutics”. Medical laser applications represent a constantly growing part of the photonic market, more recently driven by diagnostics than therapy. And the story carries on and the wheel continues to turn. Compact lasers with high effectiveness and reliability at comparably low costs have become available and new wavelengths are being added “daily” which are opening up new future perspectives. To transform a laser into a successful medical device requires intense and careful cooperation between industry and research coupled with commitment and a feeling for the right moment. Evaluation of medical and social benefits, the power of competing techniques, rules and regulations, financing and reimbursement issues all play their role in the development and placement of a medically approved device or procedure. Furthermore all medical procedures need continuous reevaluation with respect to competing techniques and to their usefulness and clinical outcome. This panel will focus on how cooperation can ensure the success of biophotonic innovations from bench to bedside with the help of clinicians, researchers, engineers and innovators from industry. Medical, scientific and industrial representatives will provide information about their specific tasks and their efforts to launch a specific device or procedure.
{"title":"LASER World of PHOTONICS – DGLM Application Panel: Laser-advanced new methods for diagnostics and therapeutics","authors":"C. Philipp, R. Sroka","doi":"10.1515/PLM-2015-0011","DOIUrl":"https://doi.org/10.1515/PLM-2015-0011","url":null,"abstract":"As part of the LASER World of PHOTONICS Congress and Exhibition, which will be held from 22 to 25 June 2015 at the International Congress Centre Munich, the Deutsche Gesellschaft für Lasermedizin (DGLM) e.V. is organizing an application panel on the topic “Laser-advanced new methods for diagnostics and therapeutics”. Medical laser applications represent a constantly growing part of the photonic market, more recently driven by diagnostics than therapy. And the story carries on and the wheel continues to turn. Compact lasers with high effectiveness and reliability at comparably low costs have become available and new wavelengths are being added “daily” which are opening up new future perspectives. To transform a laser into a successful medical device requires intense and careful cooperation between industry and research coupled with commitment and a feeling for the right moment. Evaluation of medical and social benefits, the power of competing techniques, rules and regulations, financing and reimbursement issues all play their role in the development and placement of a medically approved device or procedure. Furthermore all medical procedures need continuous reevaluation with respect to competing techniques and to their usefulness and clinical outcome. This panel will focus on how cooperation can ensure the success of biophotonic innovations from bench to bedside with the help of clinicians, researchers, engineers and innovators from industry. Medical, scientific and industrial representatives will provide information about their specific tasks and their efforts to launch a specific device or procedure.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"32 5","pages":"203 - 203"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72583770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Personalized medicine is revolutionizing modern health care. The aim of personalized diagnostics is to provide rapid, portable and simple tests that will reduce diagnosis time. They enable rapid analysis performed near the patient and provide specific details of the patient’s condition so that a personalized treatment can be made. This review focuses on the recent advances in optical diagnostic techniques based on surface plasmon resonance (SPR) and surface-enhanced Raman scattering spectroscopy (SERS) for translational medical diagnostics. In the first part, recent developments in SPR biosensors for infectious disease diagnosis are presented including the first two-dimensional multiplex influenza SPR biosensor for H1N1 (influenza A) and H3N2 (seasonal influenza) detection. In the second part, advances in SERS, which is another ultra-sensitive optical diagnostic technique for various cancer detection applications in pre-clinical and clinical settings, are reviewed.
{"title":"Recent advances in SPR and SERS for sensitive translational medical diagnostics","authors":"Chi Lok Wong, U. Dinish, M. Olivo","doi":"10.1515/plm-2014-0009","DOIUrl":"https://doi.org/10.1515/plm-2014-0009","url":null,"abstract":"Abstract Personalized medicine is revolutionizing modern health care. The aim of personalized diagnostics is to provide rapid, portable and simple tests that will reduce diagnosis time. They enable rapid analysis performed near the patient and provide specific details of the patient’s condition so that a personalized treatment can be made. This review focuses on the recent advances in optical diagnostic techniques based on surface plasmon resonance (SPR) and surface-enhanced Raman scattering spectroscopy (SERS) for translational medical diagnostics. In the first part, recent developments in SPR biosensors for infectious disease diagnosis are presented including the first two-dimensional multiplex influenza SPR biosensor for H1N1 (influenza A) and H3N2 (seasonal influenza) detection. In the second part, advances in SERS, which is another ultra-sensitive optical diagnostic technique for various cancer detection applications in pre-clinical and clinical settings, are reviewed.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"26 1","pages":"119 - 149"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84092021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sensors in diagnostics and monitoring","authors":"J. Helfmann, U. Netz","doi":"10.1515/plm-2015-0012","DOIUrl":"https://doi.org/10.1515/plm-2015-0012","url":null,"abstract":"","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"17 1","pages":"107 - 109"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78673956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background and objective: To evaluate a novel skin tone meter (STM) to categorize skin tones into one of the six categories of the Fitzpatrick skin type (FST) classification system, thus optimizing safety in light-based dermatological procedures. This numerical classification method measures several components; principally the reaction of human skin to ultraviolet (UV) light exposure, which is used to help predict skin response in laser and intense pulsed light (IPL) treatments. Materials and methods: Two-hundred twenty volunteers of varying ethnic origin, age and gender were enrolled in a preliminary study. The subjects’ Fitzpatrick skin type was ascertained by a standardized questionnaire that determined their reaction to significant sunlight exposure. A calibrated prototype STM device (consisting of an optical head at 460 nm, detector, microprocessor, and a liquid crystal display) was used to measure the subjects’ inner arm skin; which typically has little UV exposure and minimal hair, and compared the obtained value with measurements taken from a skin color chart and digital photographs. To evaluate device performance (within subject) across different skin states, a section of skin from the inner arm of a sub-group of eight volunteers was marked into test areas using a template. The skin in each area was then prepared (i) with a control area, (ii) by degreasing with acetone for 1 min to represent dry skin, (iii) with a fine layer of coupling gel to represent hydrated skin, (iv) with a thin layer of petrolatum (Vaseline) to represent oily skin, and (v) with saline solution applied then dried to represent dried perspiration. Results: There was a consistent trend between the STM prototype and the assessed skin tone derived from a proprietary skin color chart against the measurement on skin across a range of skin conditions. Conclusion: The presented preliminary study demonstrated the subjective nature of the FST classification system and the weakness of skin tone self-assessment by an individual, as judged by expert assessors. The FST classification requires an objective measurement to replace the textual description for each skin tone. It may significantly decrease the risk of potential side effects through overtreatment, and extend treatment to a wider patient population with light-based dermatological procedures.
{"title":"Evaluation of a novel skin tone meter and the correlation between Fitzpatrick skin type and skin color","authors":"C. Ash, G. Town, P. Bjerring, Samuel Webster","doi":"10.1515/plm-2013-0056","DOIUrl":"https://doi.org/10.1515/plm-2013-0056","url":null,"abstract":"Abstract Background and objective: To evaluate a novel skin tone meter (STM) to categorize skin tones into one of the six categories of the Fitzpatrick skin type (FST) classification system, thus optimizing safety in light-based dermatological procedures. This numerical classification method measures several components; principally the reaction of human skin to ultraviolet (UV) light exposure, which is used to help predict skin response in laser and intense pulsed light (IPL) treatments. Materials and methods: Two-hundred twenty volunteers of varying ethnic origin, age and gender were enrolled in a preliminary study. The subjects’ Fitzpatrick skin type was ascertained by a standardized questionnaire that determined their reaction to significant sunlight exposure. A calibrated prototype STM device (consisting of an optical head at 460 nm, detector, microprocessor, and a liquid crystal display) was used to measure the subjects’ inner arm skin; which typically has little UV exposure and minimal hair, and compared the obtained value with measurements taken from a skin color chart and digital photographs. To evaluate device performance (within subject) across different skin states, a section of skin from the inner arm of a sub-group of eight volunteers was marked into test areas using a template. The skin in each area was then prepared (i) with a control area, (ii) by degreasing with acetone for 1 min to represent dry skin, (iii) with a fine layer of coupling gel to represent hydrated skin, (iv) with a thin layer of petrolatum (Vaseline) to represent oily skin, and (v) with saline solution applied then dried to represent dried perspiration. Results: There was a consistent trend between the STM prototype and the assessed skin tone derived from a proprietary skin color chart against the measurement on skin across a range of skin conditions. Conclusion: The presented preliminary study demonstrated the subjective nature of the FST classification system and the weakness of skin tone self-assessment by an individual, as judged by expert assessors. The FST classification requires an objective measurement to replace the textual description for each skin tone. It may significantly decrease the risk of potential side effects through overtreatment, and extend treatment to a wider patient population with light-based dermatological procedures.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"80 1","pages":"177 - 186"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83836396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background and objective: Enamel irradiation with an erbium,chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has been reported to cause micromorphological alterations within resin-enamel interfaces and subsurface enamel. The present study was conducted to evaluate the effects of different output power/pulse repetition rate parameter combinations of Er,Cr:YSGG laser on the micromorphology of resin-enamel interfaces and subsurface enamel. Materials and methods: Thirty-five bovine incisors were used in the present study. Er,Cr:YSGG laser was used on enamel with different output power/pulse repetition rate parameter combinations as follows: 6 W/20 Hz, 6 W/35 Hz, 6 W/50 Hz, 3 W/20 Hz, 3 W/35 Hz, 3 W/50 Hz. Following adhesive and composite procedures, specimens were sectioned and either acid-etched with 37% phosphoric acid for 1 min or immersed in 55% nitric acid for 12 h. Then the resin-enamel interfaces were investigated by scanning electron microscopy (SEM). Results: Micromorphological findings by SEM revealed that when enamel surfaces were irradiated with all 6-W groups and 3 W/20 Hz-combinations, large resin structures indicating subsurface microcracks were generally evident within interfaces and subsurface enamel. However, when irradiated with 3 W/35 Hz and 3 W/50 Hz-combinations, the observed resin-enamel interfaces were similar to those of the acid-etched only group. Conclusion: Deploying Er,Cr:YSGG laser with lower power and high pulse repetition rate combinations may reduce damage to resin-enamel interfaces and subsurface enamel. However, assessment of the relationship between these findings and bond strength requires further study.
{"title":"Evaluation of resin-enamel interface micromorphology in respect of different Er,Cr:YSGG laser parameters","authors":"M. Ayar","doi":"10.1515/plm-2014-0029","DOIUrl":"https://doi.org/10.1515/plm-2014-0029","url":null,"abstract":"Abstract Background and objective: Enamel irradiation with an erbium,chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has been reported to cause micromorphological alterations within resin-enamel interfaces and subsurface enamel. The present study was conducted to evaluate the effects of different output power/pulse repetition rate parameter combinations of Er,Cr:YSGG laser on the micromorphology of resin-enamel interfaces and subsurface enamel. Materials and methods: Thirty-five bovine incisors were used in the present study. Er,Cr:YSGG laser was used on enamel with different output power/pulse repetition rate parameter combinations as follows: 6 W/20 Hz, 6 W/35 Hz, 6 W/50 Hz, 3 W/20 Hz, 3 W/35 Hz, 3 W/50 Hz. Following adhesive and composite procedures, specimens were sectioned and either acid-etched with 37% phosphoric acid for 1 min or immersed in 55% nitric acid for 12 h. Then the resin-enamel interfaces were investigated by scanning electron microscopy (SEM). Results: Micromorphological findings by SEM revealed that when enamel surfaces were irradiated with all 6-W groups and 3 W/20 Hz-combinations, large resin structures indicating subsurface microcracks were generally evident within interfaces and subsurface enamel. However, when irradiated with 3 W/35 Hz and 3 W/50 Hz-combinations, the observed resin-enamel interfaces were similar to those of the acid-etched only group. Conclusion: Deploying Er,Cr:YSGG laser with lower power and high pulse repetition rate combinations may reduce damage to resin-enamel interfaces and subsurface enamel. However, assessment of the relationship between these findings and bond strength requires further study.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"104 1","pages":"102 - 93"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82511184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract 5-Aminolevulinic acid (ALA)-induced photodynamic therapy (ALA-PDT) has achieved remarkable research accomplishments over the past 30 years, yet its application in medical oncology still awaits clear recognition as a valid alternative therapeutic modality. It is well documented that topical ALA-PDT enables the treatment of multiple skin lesions simultaneously, and provides excellent cosmetic results with no acquired multi-drug resistance (MDR). Furthermore, upon disease recurrence the treatment can be repeated resulting in the same therapeutic efficacy. Additionally, in oncological surgery, ALA fluorescence-guided resection is a practical and simple method for visualizing intra-operative brain and urological tumors with millimeter accuracy. The urgent challenge is to direct future research of ALA-phototherapy and fluorescence diagnosis to the maturation of their medical status in oncology. Therefore, the future objectives are to amplify critical evidence-based results of ALA-PDT safety and efficacy and to validate its unique advantages over other technologies. Strong statistical PDT documentation and the positive predictive values of protoporphyrin IX (PpIX)-guided surgery will persuade the medical community to implement ALA-based therapeutics into standard clinical and surgical oncology practice. Research must address the phenomenon that no MDR develops as a consequence of PDT, since MDR is the major stumbling block in oncological therapeutics. A feasible goal should be to improve ALA administration protocols based on recent knowledge that preactivation of the enzyme porphobilinogen deaminase enhances PpIX accumulation in cancer cells and photodestruction. Moreover the recent introduction of multifunctional ALA prodrugs that maximize photosensitizer biosynthesis, targeting multiple sub-cellular targets, may increase PDT anti-cancer efficacy in additional disease settings. In conclusion, well-documented clinical results, new ALA delivery protocols, and novel multifunctional ALA prodrugs may advance ALA-PDT to becoming a front-line cancer therapy.
{"title":"Pros, cons and future prospects of ALA-photodiagnosis, phototherapy and pharmacology in cancer therapy – A mini review","authors":"Z. Malik","doi":"10.1515/plm-2014-0036","DOIUrl":"https://doi.org/10.1515/plm-2014-0036","url":null,"abstract":"Abstract 5-Aminolevulinic acid (ALA)-induced photodynamic therapy (ALA-PDT) has achieved remarkable research accomplishments over the past 30 years, yet its application in medical oncology still awaits clear recognition as a valid alternative therapeutic modality. It is well documented that topical ALA-PDT enables the treatment of multiple skin lesions simultaneously, and provides excellent cosmetic results with no acquired multi-drug resistance (MDR). Furthermore, upon disease recurrence the treatment can be repeated resulting in the same therapeutic efficacy. Additionally, in oncological surgery, ALA fluorescence-guided resection is a practical and simple method for visualizing intra-operative brain and urological tumors with millimeter accuracy. The urgent challenge is to direct future research of ALA-phototherapy and fluorescence diagnosis to the maturation of their medical status in oncology. Therefore, the future objectives are to amplify critical evidence-based results of ALA-PDT safety and efficacy and to validate its unique advantages over other technologies. Strong statistical PDT documentation and the positive predictive values of protoporphyrin IX (PpIX)-guided surgery will persuade the medical community to implement ALA-based therapeutics into standard clinical and surgical oncology practice. Research must address the phenomenon that no MDR develops as a consequence of PDT, since MDR is the major stumbling block in oncological therapeutics. A feasible goal should be to improve ALA administration protocols based on recent knowledge that preactivation of the enzyme porphobilinogen deaminase enhances PpIX accumulation in cancer cells and photodestruction. Moreover the recent introduction of multifunctional ALA prodrugs that maximize photosensitizer biosynthesis, targeting multiple sub-cellular targets, may increase PDT anti-cancer efficacy in additional disease settings. In conclusion, well-documented clinical results, new ALA delivery protocols, and novel multifunctional ALA prodrugs may advance ALA-PDT to becoming a front-line cancer therapy.","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"14 1","pages":"19 - 26"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81854274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background: Protoporphyrin IX (PpIX)-induced photodynamic therapy (PDT) is being utilised as a topical method of localised ablation of certain non-melanoma skin cancers and precancers. Standardised protocols have been implemented to good effect when the disease remains superficial but improvement is required to treat thicker or acrally located conditions. Concurrent administration of an iron chelator during PpIX-PDT has been demonstrated to increase cellular accumulation of PpIX by reducing its bioconversion to haem (an iron dependent process) thus increasing cell kill on subsequent irradiation. Iron however, can also play a role in reactive oxygen species (ROS) generation and limiting its availability via chemical chelation could theoretically reduce the efficacy of PpIX-PDT, so that a response less than that maximally feasible is produced. Materials and methods: The effects of iron availability and chelation on PpIX-PDT have therefore been investigated via fluorescence quantification of PpIX accumulation, single-cell gel electrophoresis (comet assay) measurement of ROS-induced DNA damage and trypan blue exclusion assessment of cell viability. Cultured human cells were utilised and incubated in standardised iron conditions with the PpIX precursor’s aminolaevulinic acid (ALA) or its methyl ester (MAL) in the presence or absence of either of the iron chelating agents desferrioxamine (DFO) or hydroxypyridinone (CP94), or alternatively iron sulphate as a source of iron. Results: ALA or MAL incubation was found to significantly increase cellular PpIX accumulation pre-irradiation as anticipated and this observation correlated with both significantly increased DNA damage and reduced cellular viability following irradiation. Co-incubation with either of the iron chelators investigated (DFO or CP94) significantly increased pre-irradiation PpIX accumulation as well as DNA damage and cell death on irradiation indicating the positive effect of iron chelation on the effectiveness of PpIX-induced PDT. The opposite effects were observed however, when the cells were co-incubated with iron sulphate, with significant reductions in pre-irradiation PpIX accumulation (ALA only) and DNA damage (ALA and MAL) being recorded indicating the negative effects excessive iron can have on PpIX-PDT effectiveness. Some dark toxicity produced by iron sulphate administration in non-irradiated control groups was also observed. Conclusion: Iron chelation and availability have therefore been observed to positively and adversely affect the PpIX-PDT process respectively and it is concluded that the effects of increased PpIX accumulation pre-irradiation produced via iron chelation outweigh any limitations reduced iron availability may have on the ability of iron to catalyse ROS generation/cascades following PpIX-induced PDT. Further investigation of iron chelation within dermatological applications where enhanced PpIX-PDT treatment effects would be beneficial is therefore warr
{"title":"The importance of iron chelation and iron availability during PpIX-induced photodynamic therapy","authors":"A. Curnow, A. Pye","doi":"10.1515/plm-2014-0034","DOIUrl":"https://doi.org/10.1515/plm-2014-0034","url":null,"abstract":"Abstract Background: Protoporphyrin IX (PpIX)-induced photodynamic therapy (PDT) is being utilised as a topical method of localised ablation of certain non-melanoma skin cancers and precancers. Standardised protocols have been implemented to good effect when the disease remains superficial but improvement is required to treat thicker or acrally located conditions. Concurrent administration of an iron chelator during PpIX-PDT has been demonstrated to increase cellular accumulation of PpIX by reducing its bioconversion to haem (an iron dependent process) thus increasing cell kill on subsequent irradiation. Iron however, can also play a role in reactive oxygen species (ROS) generation and limiting its availability via chemical chelation could theoretically reduce the efficacy of PpIX-PDT, so that a response less than that maximally feasible is produced. Materials and methods: The effects of iron availability and chelation on PpIX-PDT have therefore been investigated via fluorescence quantification of PpIX accumulation, single-cell gel electrophoresis (comet assay) measurement of ROS-induced DNA damage and trypan blue exclusion assessment of cell viability. Cultured human cells were utilised and incubated in standardised iron conditions with the PpIX precursor’s aminolaevulinic acid (ALA) or its methyl ester (MAL) in the presence or absence of either of the iron chelating agents desferrioxamine (DFO) or hydroxypyridinone (CP94), or alternatively iron sulphate as a source of iron. Results: ALA or MAL incubation was found to significantly increase cellular PpIX accumulation pre-irradiation as anticipated and this observation correlated with both significantly increased DNA damage and reduced cellular viability following irradiation. Co-incubation with either of the iron chelators investigated (DFO or CP94) significantly increased pre-irradiation PpIX accumulation as well as DNA damage and cell death on irradiation indicating the positive effect of iron chelation on the effectiveness of PpIX-induced PDT. The opposite effects were observed however, when the cells were co-incubated with iron sulphate, with significant reductions in pre-irradiation PpIX accumulation (ALA only) and DNA damage (ALA and MAL) being recorded indicating the negative effects excessive iron can have on PpIX-PDT effectiveness. Some dark toxicity produced by iron sulphate administration in non-irradiated control groups was also observed. Conclusion: Iron chelation and availability have therefore been observed to positively and adversely affect the PpIX-PDT process respectively and it is concluded that the effects of increased PpIX accumulation pre-irradiation produced via iron chelation outweigh any limitations reduced iron availability may have on the ability of iron to catalyse ROS generation/cascades following PpIX-induced PDT. Further investigation of iron chelation within dermatological applications where enhanced PpIX-PDT treatment effects would be beneficial is therefore warr","PeriodicalId":20126,"journal":{"name":"Photonics & Lasers in Medicine","volume":"18 1","pages":"39 - 58"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80967695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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