Light delivery and light dosimetry for photodynamic therapy - RePub

160 Pages·2009·4 MB·English

Light delivery and light dosimetry
for photodynamic therapy of
bronchogenic carcinoma
Lars H.P. Murrer
Cover: Light dosimetry and thermometry device developed by the author
and Jerry van del' Ploeg for (pre- )clinical measurements.
Light delivery and light dosimetry
for photodynamic therapy of
bronchogenic carcinoma
Lichtapplicatie en lichtdosimetrie voor fotodynamische therapie van
kanker van de bovenste luchtwegen
Proefschrift
Ter verkrijging van de graad van doctor
aan de Erasmus Universiteit Rotterdam
op gezag van de rector magnificus
Prof. dr P.W.C. Akkermans M.A.
en volgens het besluit van het college voor promoties.
De openbare verdediging zal plaatsvinden op
woensdag 4 februari 1998 om 1345 uur
door
Lars Henri Petra Murrer
geboren 12 april 1966 te Maastricht
Promotiecommissie
Promotor Prof. dl' P.C. Levendag
Overige Leden Prof. dl' ir M.J.C. Van Gemert
Prof. dl' B. Löwenberg
Dl' ir G.J. Puppels
Co-Promotor Dl' W.M. Star
Voor Allll en Stijn
This thesis has been prepared at:
Department of Clinical Physics
Daniel den Hoed Cancel' Centre
University Hospital Rotterdam
The Netherlands
This work was kindly sponsored by:
+ OUTCH CANCER SOCIETY
RARE EARTH MEDICAL, INC.
Q!tantaNova
Address for correspolldence:
Lars HP MUITer
Dept. of Clinical Physics
Dalliel den Hoed Cancer Centre
University Hospital Rotterdam
PO Box 5201
3008 AE Rotterdam
Thc Netherlallds
Phone: [phone]
Fax: [phone]
E-mail:
Contents
1 General Introduction 3
2 Ex vivo light dosimetry and Monte Cat'lo simulations for
endobronchial Photodynamic Therapy 11
3 Light distribution by linear diffusing sources for Photody-
namic Therapy 29
4 Note: Improvements in the design of linear diffusers for
Photodynamic Therapy 45
5 Applicatol' for light delivery and in situ light dosimetry
during endobronchial Photodynamic Therapy: fh'st measu-
rements in hu mans 51
6 Monte Carlo simulations for EndoBronchial PhotoDynamic
Therapy: The influence of variations in optical and geome-
trical properties and of realistic and eccentric light sources, 65
7 Short- and long-term normal tissue damage with Photo-
dynamic therapy in pig trachea: A fluence-response study
comparing Photofrin and mTHPC 89
8 Photodynamic Therapy as Adjuvant Therapy in Surgically
Treated Pleural Malignancies 117
Summary and Concluding Remarks 139
1
2 CONTENTS
Samenvatting 145
List of publications 152
Nawoord 153
Curriculum Vitre 154
Chapter 1
General Introduction
3
4 Ligllt delivel'Y and dosimetJT [OT EndoBronchial PDT
Photodynamic Therapy
Photodynamic tllel'apy (PDT) is a treatment modality for malignant (and
benign) diseases that combines administration of a chemical compound
(photosensitiser) and irradiation with (visible) light of the proper wave-
length and fluence to induce tissue necrosis. The mechanisms by. which
PDT induces cell death are not yet fully understood. The basic principle
is that the iIIumination of the sensitiser causes excitation of the oxygen
present in the tissue to the very reactive singlet state that induces damage
to the tissue. The oxygen supply in the treated tissue is therefore of para-
mount importance for the final damage induced. Two types of damage are
thought to be most important for the induced necrosis. Firstly, important
(tumour)cell structures such as mitochondrial and cellular membranes are
damaged with consequent direct cell death. Secondly, through damage of
the endothelium of the blood vessels vascular stasis occurs which causes
tissue damage as a secondary process.
The photosensitiser can be one single molecule like mTHPC (meta-Tetra-
Hydroxy-Phenyl-Chlorin) or a mixture of several photo-active compounds
as is the case with Photofrin. Instead of using exogenous photosensitisers,
photosensitivity can also be generated in the living tissue by the induc-
tion of the formation of an endogenous photosensitiser ProtoPorphyrin IX
(PPIX). This is achieved by administering ALA (5-amino-levulinic-acid),
which intervenes in a feedback mechanism of the cycle of haem synthesis,
thereby inducing excess fOl'mation of PPIX, which can then be used for
photodynamic therapy.
The majority of the sensitisers is activated with red light ("" 630 nm for
PPIX and Photofrin, 652 nm for mTHPC). Sometimes green light (514 nm)
is also applied because some sensitisers (eg. Photofrin, PPIX) have stronger
absorption at that wavelengtil. The penetration of green light in tissue is
very limited ("" 1 mm) becanse of the strong absorption by blood. For the
treatment of thick lesions this is a disadvantage but for the treatment of
the superficiallesions in the oesophagus, however, the Iimited penetration
depth of the green light is an advantage because it prevents perforations.
In the ideal case, the photosensitiser accumulates preferentially in the target
tissue, and selective treatment of the target (tumour) tissue is possible.
U nfortunately, most photosensitisers do not show these ideal localisation
properties. A drawback of the use of photosensitisers is the fact that the
clearance of the compound from the body can take some time (up to months
with Photofrin), and during this period precautions most be taken to avoid