Table Of ContentMETHODS IN
PORPHYRIN
PHOTOSENSITIZATION
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
NICHOLAS R. DI LUZIO, Tulane University School of Medicine
EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science
DA VID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, Rockland Research Institute
RODOLFO PAOLETTI, University of Milan
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METHODS IN PORPHYRIN PHOTOSENSITIZATION
Edited by David Kessel
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METHODS IN
PORPHYRIN
PHOTOSENSITIZATION
Edited by
David Kessel
Wayne State University School of Medicine
Detroit, Michigan
PLENUM PRESS. NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Porphyrin Photosensitization Workshop (1984: Wayne State University)
Methods in porphyrin photosensitization.
"Proceedings of the Porphyrin Photosensitization Workshop, held July 6-7, 1984, in
Philadelphia, Pennsylvania" - T.p. verso.
Bibliography: p.
Includes index.
1. Photochemotherapy-Congresses. 2. Cancer-Radiotherapy-Congresses. 3. Por
phyrin and porphyrin compounds-Therapeutic use-Congresses. 4. Porphyrin and
porphyrin compounds - Diagnostic use -Congresses. 5. Photosensitization, Biological
-Congresses. I. Kessel, David. II. Title. III. Series. [DNLM: 1. Photochemotherapy
methods - congresses. 2. Porphyrins - pharmacodynamics - congresses. 3. Porphyrins
-therapeutic use-congresses. QU 110 P8372m 1984]
RC271. P43P67 1984 615.5'8 85-25627
ISBN-13: 978-1-4612-9276-0 e-ISBN-13: 978-1-4613-2165-1
DOl: 10.1007/978-1-4613-2165-1
Proceedings of the Porphyrin Photosensitization workshop, held July 6-7, 1984,
in Philadelphia, Pennsylvania
© 1985 Plenum Press, New York
Softcover reprint ofthe hardcover 1st edition 1985
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N. Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
Porphyrin localization in vitro
Photographs of L1210 cells obtained by fluorescence microscopy. Left: after 10 min
incubation with HPD, showing the diffuse peripheral fluorescence associated with
drug accumulation at membrane loci. Right: after 24 hr incubation with HPD
followed by washing to remove readily-diffusible porphyrins, showing intracellular
sites of sensitizer binding. For further details of this experiment, see p. 223.
PREFACE
The use of porphyrins for localization and photodynamic therapy of
neoplastic disease has been the topic of several international symposia,
reviews and books during the preceeding five years. The literature on
this topic has continued to grow, as have numbers of presentations at
national and international meetings relating to photobiology, chemistry,
and lasers. In this volume, it is the intention of the editor to provide
both information on current research projects, and detailed methodology
used in such investigations. A bibliography on the subjects of porphyrin
localization and therapy is included.
The manuscripts contained in this volume are based on reports given
at a Porphyrin Photosensitization Workshop which was held in Philadel
phia, July 6-7, 1984. This Workshop was supported by NIH grant CA
36746, together with funds from the Fogarty International Center.
Authors were requested to update their contributions to provide a summary
of progress to mid 1985. Manuscripts containing material not presented
in Philadelphia are also included, notably a series of articles describ
ing current clinical and pre-clinical results from China. Since the
Philadelphia Workshop, a meeting was held in Alghero, Sardinia (May,
1985), and additional conferences are now being planned; this attests to
the continued interest in photodynamic therapy involving porphyrin photo
sensitization.
The successful development of this modality has required communica
tion among a variety of workers in diverse fields. These include porphy
rin chemistry, photochemistry, and photobiology, analytical chemistry,
biophysics, pharmacology, surgery and medicine. While the clinical
progress in photodynamic therapy was a major objective, a byproduct has
been the mingling of workers from many different disciplines, with
resulting collaborations sometimes extending to unrelated topics.
The use of porphyrins for tumor-localization had its beginnings in
work reported by Lipson 25 years ago. This involved a collaborative ef
fort with Dr. Samuel Schwartz, at the Mayo Clinic, which yielded a por
phyrin product termed HPD (hematoporphyrin derivative) which was then,
and still remains, the most effective tumor photosensitizer known. This
work was of little initial interest to the biomedical field, since ap
propriate instrumentation for its exploitation was not available until
the development of lasers and optical fibers for light distribution. But
v
a small group of workers continued to examine porphyrin-tumor affinity
relationships, generally with little outside support.
The current cascade of research projects, literature reports and
conferences was initiated by a series of investigations by Dr. T.J.
Dougherty, at the Roswell Park Memorial Institute in Buffalo. Dougherty
provided a reliable source of drug, together with information on light
sources, clinical protocols, and other information to interested inves
tigators. A series of pioneering physicians, notably James Kennedy in
Ontario, Ian Forbes in Australia, Oscar Balchum in Los Angeles, Yoshihiro
Hayata in Japan, and Denis Cortese at the Mayo Clinic, provided the early
results which stimulated additional research. Because of this concerted
effort, many of the fundamentals of porphyrin photosensitization have
been reported, and guidelines for further work are clearly visible. This
volume is intended to provide a reference for further studies in the
field of porphyrin phototherapy, as well as an description of the current
status of selected fields of research.
David Kessel
CONTENTS
HEMATOPORPHYRIN PHOTODYNAMIC THERAPY FOR TRANSITIONAL
CELL CARCINOMA OF THE BLADDER - AN UPDATE ••...•. 3
R.C. Benson, Jr.
PHOTODYNAMIC THERAPY IN THE MANAGEMENT OF CANCER:
AN ANALYSIS OF 114 CASES •.••.••.••••. 13
W-M. Cai, Y. Yang, N-W. Zhang, J-G. Xie, X. Zhang,
X-J. Fan, H. Shen, X-J. Hu, and X-W. Ha
PRELIMINARY RESULTS OF HEMATOPORPHYRIN DERIVATIVE-LASER TREATMENT
FOR 13 CASES OF EARLY ESOPHAGEAL CARCINOMA. . • • . . • • . . . 21
M-E. Tian, S-L. Qui and Q. Ji
OPTIMALIZATION OF THE DEPTH OF SELECTIVE RESPONSE
OF NEOPLASTIC TISSUE ......•...•...• 27
L.O. Svaasand
DOSIMETRY METHODS IN PHOTORADIATION THERAPY 35
A.E. Profio, L.R. Wudl and J. Sarnaik
FLUORESCENCE DIAGNOSIS OF CANCER 43
A.E. Profio and O.J. Balchum
STUDIES OF HPD AND RADIOLABELLED HPD IN VIVO AND IN VITRO 51
W.P. Jeeves, B.C. Wilson, G. Firnau and~ Brown
PHOTODYNAMIC EFFECTS AND HYPERTHERMIA IN VITRO. 69
T. Christensen, L. Smedshammer, A. Wahl and J. Moan
PRELIMINARY STUDIES WITH IMPLANTED POLYVINYL ALCOHOL SPONGES AS A
MODEL FOR STUDYING THE ROLE OF NEOINTERSTITIAL AND NEOVASCULAR
COMPARTMENTS OF TUMORS IN THE LOCALIZATION, RETENTION AND
PHOTODYNAMIC EFFECTS OF PHOTOSENSITIZERS • . . . . . • • . • . 77
R.C. Straight and J.D. Spikes
vii
QUANTITATIVE STUDIES OF TETRAPHENYLPORPHINESULFONATE AND HEMATO-
PORPHYRIN DERIVATIVE DISTRIBUTION IN ANIMAL TUMOR SYSTEMS 91
J.W. Winkelman
~ORRELATION OF TUMOR BLOOD FLOW TO TUMOR REGRESSION AFTER HEMATO
PORPHYRIN DERIVATIVE (HPD) PHOTODYNAMIC THERAPY TO TRANSPLANTABLE
BLADDER TUMORS . . . . . . . . . . . • . . • • . . 97
S.H Selman, M. Kreimer-Birnbaum, R.W. Keck, A.J. Mi Iligan,
P.J. Goldblatt and S. Britton
THE BIOLOGICAL EFFECTS OF PHOTODYNAMIC THERAPY ON NORMAL SKIN IN
MICE-I. A LIGHT MICROSCOPIC STUDY. • . . . . • • . • 105
C. Zhou, W. Yang, Z. Ding, Y. Wang, H. Shen, X. Fan and X. Ha
THE BIOLOGICAL EFFECTS OF PHOTODYNAMIC THERAPY ON NORMAL SKIN IN
MICE-II. AN ELECTRON MICROSCOPIC STUDY . . . . • . • III
C. Zhou, W. Yang, Z. Ding, Y. Wang, H. Shen, X. Fan and X. Ha
STUDIES ON HEMATOPORPHYRIN PHOTOSENSITIZED EFFECTS ON
HUMAN CANCER CELLS IN VITRO: TEM AND SEM OBSERVATIONS 117
A-L. Ning and Q-Q. Pan
PHOTODYNAMIC EFFECT OF HEMATOPORPHYRIN ON HUMAN CANCER CELLS
AND NORMAL DIPLOID FIBROBLASTS IN VITRO " . • . . . 123
Q. Pan, M. Fu and X. Zhao
PHOTOTOXIC EFFECTS OF HEMATOPORPHYRIN DERIVATIVE AND ITS
CHROMATOGRAPHIC FRACTIONS ON HORMONE-PRODUCING MALIGNANT
TROPHOBLAST CELLS IN VITRO .•............. 129
A.W. Girotti and R.O. Huses
EXAMINATION OF POTENTILLY LETHAL DAMAGE IN CELLS TREATED WITH
HEMATOPORPHYRIN DERIVATIVE AND RED LIGHT. . • . • . • . 147
C.J. Gomer, N. Rucker and A.L. Murphree
PORPHYRIN PHOTOSENSITIZATION OF BACTERIA. 155
B. Kjeldstad, T. Christensen and A. Johnsson
PHOTOSENSITIZATION OF MITOCHONDRIAL ADENOSINE-TRIPHOSPHATE
AND ADENYLATE KINASE BY HEMATOPORPHYRIN DERIVATIVE IN VIVO 161
N.W. Fu, S.Y. Yeh, C. Chang, X.H. Zhao and L.S. Chang
PORPHYRIN-MEMBRANE INTERACTIONS: STRUCTURAL, KINETIC AND
THERMODYNAMIC ASPECTS STUDIED USING FLUORESCENCE TECHNIQUES 169
R.C. Chatelier, W.H. Sawyer, A.G. Swincer and A.D. Ward
PHOTOPHYSICS AND PHOTOCHEMISTRY OF HEMATOPORPHYRIN,
HEMATOPORPHYRIN DERIVATIVE AND UROPORPHYRIN I 181
L. I. Grossweiner, A. Blum and G.C. Goyal
BINDING OF PORPHYRINS TO SERUM PROTEINS .... 193
J. Moan, C. Rimington, J.F. Evensen and A. Western
SEPARATION OF DIFFERENT FRACTIONS OF HEMATOPORPHYRIN
DERIVATIVE BY A TWO-PHASE EXTRACTION SYSTEM • 207
S. Sommer, J. Moan and C. Rimington
CHEMICAL, BIOLOGIC AND BIOPHYSICAL STUDIES ON
'HEMATOPORPHYRIN DERIVATIVE' .....• 213
D. Kessel, C.K. Chang and B. Musselman
viii
SOME PREPARATIONS AND PROPERTIES OF PORPHYRINS. . • . • . • •• 229
T.P. Wijesekera and D. Dolphin
THE STRUCTURE OF PROTOPORPHYRIN AND OF THE AGGREGATE FRACTION
OF HAEMATOPORPHYRIN DERIVATIVE IN SOLUTION. • • • . • • • . • 267
A.D. Ward and A.G. Swincer
CHEMICAL MANIPULATION OF THE VINYL GROUPS IN PROTOPORPHYRIN-IX 277
K. M. Smi th
AGGREGATION EFFECTS ON THE PHOTOPHYSICAL PROPERTIES OF PORPHYRINS
IN RELATION TO MECHANISMS INVOLVED IN PHOTODYNAMIC THERAPY. •. 293
R.W. Redmond, E.J. Land and T.G. Truscott
STUDIES ON THE SOLVOPHOBIC NATURE OF PORPHYRIN SELF AGGREGATION
VS. THE LIPOPHILIC NATURE OF PORPHYRIN-MEMBRANE BINDING. . . .. 303
R. Marga1it, S. Cohen and M. Rotenberg
PHOTODYNAMIC THERAPY 313
T.J. Dougherty
BIBLIOGRAPHY 329
D. Kessel
INDEX •••. 351
ix
