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Photodynamic therapy and laser-based diagnostic studies of malignant tumours

Wang, Ingrid LU (1999)
Abstract
Two non-thermal regimens of light interaction with biological tissue, that are in a natural way connected, are discussed in the present thesis. These are photodynamic therapy (PDT) for the treatment of malignant tumours and laser-induced fluorescence (LIF) for tissue characterization.



In PDT, a photochemical reaction is induced by non-ionizing electromagnetic irradiation in tissue where photosensitizing agents and oxygen are present. Instead of using pre-formed photosensitizers for intravenous administration, a new way of sensitization was exploited. A porphyrin precursor, (delta)-aminolevulinic acid (ALA) was utilized for the induction of protoporphyrin IX (PpIX). Photodynamic therapy was used in the treatment of... (More)
Two non-thermal regimens of light interaction with biological tissue, that are in a natural way connected, are discussed in the present thesis. These are photodynamic therapy (PDT) for the treatment of malignant tumours and laser-induced fluorescence (LIF) for tissue characterization.



In PDT, a photochemical reaction is induced by non-ionizing electromagnetic irradiation in tissue where photosensitizing agents and oxygen are present. Instead of using pre-formed photosensitizers for intravenous administration, a new way of sensitization was exploited. A porphyrin precursor, (delta)-aminolevulinic acid (ALA) was utilized for the induction of protoporphyrin IX (PpIX). Photodynamic therapy was used in the treatment of non-melanoma malignant skin tumours, mainly basal cell carcinomas (BCCs). A randomized, clinical trial was conducted in the treatment of BCCs, where PDT was compared to cryosurgery.



Laser-induced fluorescence (LIF) can be applied for non-invasive, real time spectroscopic tissue characterization. Laser light is used for fluorescence excitation. The fluorescence signal in pre-malignant and malignant tissue exhibits some characteristics that deviate from those of normal tissue. In addition, the contrast can be increased by employing fluorescent tumour markers. Laser-induced fluorescence measurements were performed in malignancies of the skin and benign, pre-malignant and malignant lesions in the head-and-neck region. Again, ALA-induced PpIX was used. The build-up and the photodegradation of PpIX were also studied.



Another non-invasive, real time method for tissue diagnostics is laser-Doppler imaging (LDI), for detection of the blood perfusion in superficial tissue. In the present work, the modality was used in connection with ALA-PDT of non-melanoma malignant skin tumours, for identifying lesions, characterize the vascular effects induced by the PDT and follow the healing process after treatment. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Två icke-termiska modaliteter utnyttjande ljusets växelverkan med biologisk vävnad beskrivs i den aktuella avhandlingen. De två modaliteterna är fotodynamisk tumörterapi (PDT) och laser-inducerad fluorescens (LIF) för vävnadsdiagnostik.



Fotodynamisk tumörterapi är en behandlingsform där ett tillfört fotosensibiliserande ämne reagerar med icke-joniserande strålning och genererar vävnadsskada i närvaro av syre. Traditionellt sett har porfyrinderivat använts som fotosensibiliserare, vilka framförallt har administrerats intravenöst. En ny metod för att sensibilisera vävnad har utnyttjats i de aktuella arbetena. En icke-fotoaktiv aminosyra, (delta)-aminolevulinsyra (ALA), tillförs... (More)
Popular Abstract in Swedish

Två icke-termiska modaliteter utnyttjande ljusets växelverkan med biologisk vävnad beskrivs i den aktuella avhandlingen. De två modaliteterna är fotodynamisk tumörterapi (PDT) och laser-inducerad fluorescens (LIF) för vävnadsdiagnostik.



Fotodynamisk tumörterapi är en behandlingsform där ett tillfört fotosensibiliserande ämne reagerar med icke-joniserande strålning och genererar vävnadsskada i närvaro av syre. Traditionellt sett har porfyrinderivat använts som fotosensibiliserare, vilka framförallt har administrerats intravenöst. En ny metod för att sensibilisera vävnad har utnyttjats i de aktuella arbetena. En icke-fotoaktiv aminosyra, (delta)-aminolevulinsyra (ALA), tillförs topiskt eller peroralt. Aminosyran ALA utgör ett förstadium till hem, inom samma syntes, där protoporfyrin IX (PpIX) utgör sista steget innan hem bildas. Protoporfyrin IX är ett fotoaktivt ämne som ansamlas i malign vävnad om ALA tillförs i överskott. Farmakokinetiken för ALA, hem och dess intermediärer är snabb och tillåter ett utnyttjande av denna form av fotosensibilisering under de första timmarna efter dosering, beroende på given dos och administreringsform. Fotodynamisk tumörterapi användes i behandlingen av olika sorters hudförändringar, framförallt basalcellscancer (BCC). En klinisk Fas III studie har utförts, där fotodynamisk tumörterapi utnyttjande ALA-inducerad PpIX jämförs med frysbehandling, en konventionell behandlingsform.



Laser-inducerad fluorescens (LIF) är en icke-invasiv metod för att karakterisera biologisk vävnad i real-tid. Laserljus i UV/nära UV området används för att excitera fluorescens i vävnaden. Fluorescenssignalen från pre-maligna och maligna förändringar skiljer sig från den i normal vävnad. Dessutom kan man tillföra starkt fluorescerande ämnen, tumörmarkörer, som till viss grad ansamlas selektivt i pre-maligna och maligna förändringar och ger ökad kontrast avseende tumör-till-normal vävnad. Mätningar utnyttjande laser-inducerad fluorescens har utförts på maligna hudtumörer samt godartade, pre-maligna och maligna förändringar i huvud-hals regionen. Som tumörmarkör har även här ALA-inducerad PpIX utnyttjats. Kinetiken avseende bildningen av PpIX från ALA har detekterats med hjälp av LIF mätningar. Protoporfyrin IX fotodegraderas under fotodynamisk tumörterapi, vilket har konsekvenser för behandlingsdosen som ges. Denna fotodegradering har också studerats utnyttjande LIF teknik.



Ytterligare en metod för att diagnostisera vävnad i real-tid med hjälp av laserljus är laser-Doppler imaging (LDI). Med LDI mäts blodgenomströmningen i de ytliga vävnadslagren genom att detektera laserljus som Doppler skiftas (frekvensen ändras) när det sprids mot röda blodkroppar i rörelse. Metoden har använts i samband med ALA-PDT och frysbehandling av hudtumörer för att identifiera förändringarna. Hur behandlingen påverkade blodflödet studerades också. Under uppföljningen av patienterna användes metoden för att följa läkningsprocessen, vilket i samband med den kliniska studien utnyttjades som ett objektivt mått på läkningstid. Samtidigt kunde eventuell kvarvarande tumörväxt identifieras. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Moan, Johan, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo
organization
publishing date
type
Thesis
publication status
published
subject
keywords
protoporphyrin IX (PpIX), (delta)-aminolevulinic acid (ALA), photosensitizer, basal cell carcinoma (BCC), Photodynamic therapy (PDT), laser-induced fluorescence (LIF), Cytology, oncology, cancerology, Cytologi, onkologi, cancer
pages
210 pages
publisher
Lund University Medical Laser Centre, Department of Oncology, Lund University Hospital
defense location
The Lecture Hall, Department of Oncology, Lund University Hospital
defense date
1999-02-18 13:15:00
external identifiers
  • other:ISRN: LUMEDW/MEOK-1025-SE
ISBN
91-628-3352-9
language
English
LU publication?
yes
additional info
Article: I. I. Wang, S. Andersson-Engels, G.E. Nilsson, K. Wårdell and K. Svanberg, Superficial blood flow following photodynamic therapy of malignant skin tumours measured by laser Doppler perfusion imaging, Br. J. Dermatol. 136, 184-189 (1997). Article: II. I. Wang, B. Bauer, S. Andersson-Engels, S. Svanberg and K. Svanberg, Photodynamic therapy utilising topical (delta)-aminolevulinic acid in non-melanoma skin malignancies of the eyelid and the periocular skin, Acta Ophthalmol. Scand. 77, in press (1999). Article: III. K. Svanberg, T. Andersson, D. Killander, I. Wang, U. Stenram, S. Andersson-Engels, R. Berg, J. Johansson and S. Svanberg, Photodynamic therapy of non-melanoma malignant tumours of the skin using topical (delta)-amino levulinic acid sensitization and laser irradiation, Br. J. Dermatol. 130, 743-751 (1994). Article: IV. I. Wang, L. Pais Clemente, R.M.G. Pratas, E. Cardoso, M. Pais Clemente, S. Montán, S. Svanberg and K. Svanberg, Fluorescence diagnostics and kinetic studies in the head and neck region utilising low-dose (delta)-aminolevulinic acid sensitisation, Cancer Letters 135, 11-19, (1999). Article: V. I. Wang, N. Bendsoe, C. af Klinteberg, A.M.K. Enejder, S. Andersson-Engels, S. Svanberg and K. Svanberg, Photodynamic therapy versus cryosurgery of basal cell carcinomas; results of a Phase III randomized clinical trial, Manuscript (1999). Article: VI. C. af Klinteberg, I. Wang, A.M.K. Enejder, S. Andersson-Engels, S. Svanberg and K. Svanberg, (delta)-Aminolevulinic acid-induced protoporphyrin IX fluorescence in basal cell carcinomas of the skin, Manuscript (1999). Article: VII. C. af Klinteberg, A.M.K. Enejder, I. Wang, S. Andersson-Engels, S. Svanberg and K. Svanberg, Kinetic fluorescence studies of (delta)-aminolevulinic acid-induced protoporphyrin IX in basal cell carcinomas, Submitted (1999). Article: VIII. A.M.K. Enejder, C. af Klinteberg, I. Wang, S. Andersson-Engels, N. Bendsoe, S. Svanberg and K. Svanberg, Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic- and cryotherapy employing laser-Doppler imaging, Submitted (1999).
id
3d1fd709-5a3a-4d09-92aa-a865544da86a (old id 39280)
date added to LUP
2016-04-04 10:44:28
date last changed
2018-11-21 21:00:32
@phdthesis{3d1fd709-5a3a-4d09-92aa-a865544da86a,
  abstract     = {Two non-thermal regimens of light interaction with biological tissue, that are in a natural way connected, are discussed in the present thesis. These are photodynamic therapy (PDT) for the treatment of malignant tumours and laser-induced fluorescence (LIF) for tissue characterization.<br/><br>
<br/><br>
In PDT, a photochemical reaction is induced by non-ionizing electromagnetic irradiation in tissue where photosensitizing agents and oxygen are present. Instead of using pre-formed photosensitizers for intravenous administration, a new way of sensitization was exploited. A porphyrin precursor, (delta)-aminolevulinic acid (ALA) was utilized for the induction of protoporphyrin IX (PpIX). Photodynamic therapy was used in the treatment of non-melanoma malignant skin tumours, mainly basal cell carcinomas (BCCs). A randomized, clinical trial was conducted in the treatment of BCCs, where PDT was compared to cryosurgery.<br/><br>
<br/><br>
Laser-induced fluorescence (LIF) can be applied for non-invasive, real time spectroscopic tissue characterization. Laser light is used for fluorescence excitation. The fluorescence signal in pre-malignant and malignant tissue exhibits some characteristics that deviate from those of normal tissue. In addition, the contrast can be increased by employing fluorescent tumour markers. Laser-induced fluorescence measurements were performed in malignancies of the skin and benign, pre-malignant and malignant lesions in the head-and-neck region. Again, ALA-induced PpIX was used. The build-up and the photodegradation of PpIX were also studied.<br/><br>
<br/><br>
Another non-invasive, real time method for tissue diagnostics is laser-Doppler imaging (LDI), for detection of the blood perfusion in superficial tissue. In the present work, the modality was used in connection with ALA-PDT of non-melanoma malignant skin tumours, for identifying lesions, characterize the vascular effects induced by the PDT and follow the healing process after treatment.},
  author       = {Wang, Ingrid},
  isbn         = {91-628-3352-9},
  language     = {eng},
  publisher    = {Lund University Medical Laser Centre, Department of Oncology, Lund University Hospital},
  school       = {Lund University},
  title        = {Photodynamic therapy and laser-based diagnostic studies of malignant tumours},
  url          = {https://lup.lub.lu.se/search/ws/files/5610871/2371689.pdf},
  year         = {1999},
}