Photodynamic Medicine

Herwig Kostron; Tayyaba Hasan

BOOK

Photodynamic Medicine

Herwig Kostron | Tayyaba Hasan

(2016)

Additional Information

Book Details

ISBN: 978-1-78262-682-4
Edition: 1
Language: English
Pages: 650
Subjects: Medical diagnosis
Medical imaging
Medicinal chemistry
Physical chemistry
Nuclear chemistry, photochemistry & radiation

Abstract

Photodynamic therapy (PDT) is increasingly being used amongst health practitioners in combating a variety of diseases. This book reviews the current state of development of PDT, and also presents the foreseeable advancements of the field in the next decade. Practitioners in biological sciences, biotechnology and medicinal and pharmaceutical chemistry will find this book an invaluable source of information.
Chapters are drawn from research discussed at the 10th International Symposium on Photodynamic Therapy and Photodiagnosis in Clinical Practice in Brixen and are written and edited by leaders in the field. Mirroring the philosophy of that meeting, this book contains an informative balance of the basic science and clinical applications of PDT. Following an introduction to PDT, its history, and how techniques have developed, chapters serve as a practical guide for practitioners, covering topics such as sensitizer dosage and light dosage, and examples of relevant studies. The text goes further to explore areas outside the medical field, such as the impact of PDT on society and the environment, and the economics of therapies.
This book is dedicated to the memory of Professor Giulio Jori, an expert in this field, who sadly passed away on the 23rd December 2014.

Section Title	Page	Action	Price
Cover	Cover
COMPREHENSIVE SERIES IN PHOTOCHEMICAL AND PHOTOBIOLOGICAL SCIENCE	i
Preface	vii
Biographies	xi
Contents	xxv
Chapter 1 - The Journey of PDT Throughout History: PDT from Pharos to Present	1
1.1.\rIntroduction	3
1.2.\rThe PDT Tree	3
1.2.1.\rThe Tree Roots (Origins of PDT)	3
1.3.\rDevelopment of PDT	6
1.4.\rDevelopment of PSs	8
1.5.\rLight Sources	12
1.6.\rRecent Trends in PDT Applications	13
1.6.1.\rTherapeutic Combinations in Which PDT Is the Core Therapeutic Partner	13
1.6.1.2.\rPDT and Chemotherapy	13
1.6.1.3.\rPDT and Radiation Therapy.Radiation therapy or RT is a treatment modality that utilizes ionizing radiation in order to d...	14
1.6.1.4.\rPDT and Immunotherapy.Any cancer treatment modality should not only destroy the tumor at its primary site, but also acti...	15
1.6.1.5.\rAngiogenesis Inhibitors.PDT may induce direct vascular damage and subsequently more extensive injury due to internalizat...	15
1.6.1.6.\rPDT and Antioxidants.The well-known mechanism of PDT action on tumorous and non-tumorous cells can be simplified by the ...	16
1.6.1.7.\rPDT and Receptor Inhibition.Cell growth is mediated through different receptors and downstream cell signaling cascades. ...	16
1.6.2.\rNanotechnology-Based PDT	17
1.6.2.2.\rNanovehicles Acting Only As PS Carriers.Nanovesicles, namely liposomes, transferosomes, niosomes and others, are tiny ve...	17
1.7.\rOther Significant Applications of PDT	18
References	18
Chapter 2 - Photosensitisers for Photodynamic Therapy: State of the Art and Perspectives	23
2.1.\rIntroduction to Photosensitisation	25
2.2.\rClinical PSs	26
2.2.1.\rPSs for Cancer Therapy	26
2.2.2.\rPSs for Antimicrobial PDT	31
2.2.3.\rPSs for Other Indications	31
2.3.\rPreclinical PSs of Natural Origin	31
2.3.1.\rTetrapyrroles	31
2.3.2.\rFlavins	35
2.3.3.\rPhenalenones	35
2.3.4.\rPerylenequinones	36
2.3.5.\rOther Families	36
2.4.\rPreclinical Synthetic PSs	36
2.4.1.\rPorphyrinoids	37
2.4.2.\rNon-Porphyrinoid PSs	38
2.5.\rActivatable PSs	39
2.5.1.\rActivation by Molecular Recognition	40
2.5.2.\rEnzyme Activation	40
2.5.3.\rpH-Sensitive PSs	40
2.5.4.\rSmall-Molecule Activation	41
2.5.5.\rPhotoactivatable PSs	41
2.5.6.\rPolarity-Sensitive PSs	41
2.5.7.\rMulti-Stimulus Responsive PSs	42
2.6.\rPhotoimmunoconjugates	42
2.6.1.\rBioconjugation Strategies	42
2.6.2.\rEarly Conjugates	43
2.6.3.\rRecent Trends	43
2.6.4.\rFluorogenic and Chromogenic Theranostic PICs	44
2.7.\rGenetically Encoded PSs	45
2.7.1.\rGFP Homologues	45
2.7.2.\rFlavin-Binding FPs	46
2.8.\rPhotosensitising Nanomaterials	46
2.8.1.\rNanomaterials as Novel Types of PSs	46
2.8.1.1.\rCarbon Nanostructures.The era of carbon nanostructures started in 1985 with the discovery of buckminsterfullerene (C60),...	47
2.8.1.2.\rPorous Silicon Nanoparticles.Among all of the metalloid materials that have been isolated as nanostructures, silicon nan...	47
2.8.1.3.\rMetal Oxide Nanoparticles.Several metal oxide nanoparticles have been reported so far as producing different ROS under i...	47
2.8.1.4.\rPlasmonic Nanoparticles.Plasmonic nanoparticles are metal nanoparticles (MNPs) with diameters of over 2–5 nm that can su...	48
2.8.2.\rNanomaterials as Light Antennas	48
2.8.2.1.\rQuantum Dots.Quantum dots (QDs) have been proposed and explored as antennas for PDT treatments given their efficiency as...	48
2.8.2.2.\rUp-Conversion Nanoparticles.Up-conversion nanoparticles (UNCs) are nanometre-sized materials composed of host lattices o...	49
2.8.2.3.\rPlasmonic Nanoparticles.The last decade has witnessed the birth and exponential growth of nanoplasmonics, whereby the un...	49
2.9.\rConclusions and Outlook	50
References	51
Chapter 3 - Basic Biological Mechanisms of Photodynamic Diagnosis/Photodynamic Therapy	63
3.1.\rIntroduction	65
3.2.\rDelivery and Transport	65
3.3.\rTumor-Selective Accumulation	66
3.4.\rCellular Uptake and Intracellular (Re)localization	66
3.5.\rEffects of the PS under Dark Conditions	68
3.6.\rPrimary Interaction of the Photoactivated PS with Cells	69
3.7.\rSurvival After PDT	70
3.8.\rCell Death After PDT	70
References	72
Chapter 4 - The Story of ALA Photodynamic Therapy: A Cancer Enigma	75
4.1.\rIntroduction	77
4.2.\rAnomalous Energy Metabolism in Tumors Is Correlated with Disturbed Heme Synthesis Pathway	77
4.2.1.\rEnergy Production in Cancer	77
4.2.2.\rDisturbed Heme Synthesis Pathway in Neoplasms	78
4.2.3.\rSpontaneous Accumulation of Porphyrins in Neoplastic Tissues	79
4.3.\rExogenous ALA Induces PpIX Synthesis and Enables Phototherapy of Tumors	79
4.3.1.\rExogenous ALA Stimulates the Synthesis of Protoporphrin IX	79
4.3.2.\rThe Activity and Expression of ALAD, PBGD and FeCh in Cancer	81
4.3.3.\rNuclear Localization of PBGD	82
4.4.\rThe Past and Future of ALA-PDT	82
References	85
Chapter 5 - The Tumor Microenvironment Modulates Responsiveness to Photodynamic Therapy	87
5.1.\rIntroduction—Remembering Giulio Jori, a True Gentleman and a Scholar	89
5.2.\rGetting PDT Research Started with In vitro and In vivo Studies	89
5.3.\rPDT Activation of Early-Response Genes	91
5.4.\rInduction of Stress Proteins Following PDT	92
5.5.\rPDT and the Tumor Vasculature-Induced Expression of VEGF	94
5.6.\rCOX-2 and the Inflammatory Response Induced by PDT	95
5.7.\rModulating PDT by Targeting HSP-90—The Role of HSP-90 Client Proteins in PDT Responsiveness	97
5.8.\rConclusions and Next Steps	98
References	98
Chapter 6 - Multifunctional Nanoparticles for Theranostic or X-Ray-Induced Photodynamic Therapy	101
6.1.\rIntroduction	103
6.2.\rState of the Art	103
6.3.\rImproving Our Strategy: The Use of Multifunctional Nanoparticles	105
6.4.\rA New Strategy: The Interest in X-Ray-Excitable Nanoparticles	107
6.5.\rConclusion	110
References	111
Chapter 7 - Metallic Nanoparticles for Targeted Delivery of Photosensitisers for Photodynamic Therapy	113
7.1.\rIntroduction	115
7.2.\rGold Nanoparticles	115
7.3.\rMagnetic Nanoparticles	127
7.4.\rConclusions	132
References	133
Chapter 8 - Targeted Photodynamic Therapy—An Assimilation of Successes, Challenges and Future Directions	137
8.1.\rIntroduction	139
8.2.\rFunctional Targeting	139
8.2.1.\rThe Enhanced Permeability and Retention Effect	139
8.2.2.\rpH and Redox Targeting	144
8.2.3.\rEnzymatic Targeting	145
8.2.4.\rTargeted Receptor Inhibition	146
8.3.\rTargeted Delivery	147
8.3.1.\rPhotoimmunoconjugates	147
8.3.2.\rTargeted Nanocarriers	149
8.4.\rTargeting Through Tissue Modulation	154
8.5.\rConclusions	157
References	157
Chapter 9 - Photochemical Internalization-Enhanced Targeting of Vasculature and Cancer Stem Cells—Present and Future Perspectives	161
9.1.\rBackground	163
9.1.1.\rGeneral Physicochemical Properties of Anticancer Drugs: Benefits and Limitations	163
9.1.2.\rMechanisms of Cellular Uptake and Intracellular Localization of Drugs	163
9.1.2.1.\rEndocytosis.There are several types of endocytosis, including pinocytosis, adsorptive endocytosis, phagocytosis and rece...	164
9.1.3.\rMethods for Endosomal Escape of Entrapped Drugs	165
9.1.3.1.\rPhotochemical Internalization.PCI is based on highly amphiphilic PSs such as the clinical used disulfonated tetraphenyl ...	165
9.2.\rPCI May Overcome Current Limitations of Anticancer Therapeutics	166
9.2.1.\rPCI of Targeted Toxins, a Strategy for Efficient and Specific Targeting of the Tumor Parenchyma	167
9.2.2.\rRapid and Specific Tumor Vascular Shutdown by PCI of VEGFR-Targeting Therapeutics	167
9.2.3.\rPCI of CSC-Targeting Toxins	168
9.2.4.\rPCI Meets Treatment Challenges with Inter- and Intra-Tumor Heterogeneity	172
9.2.4.1.\rPhotochemical Reactions Induced by the PS and Light.This mechanism of antitumor activity is the same as that induced by ...	174
9.2.4.2.\rPhotochemical Activation of a Cytotoxic Drug Within the Target Cell.This mechanism will be represented in all tumors cel...	174
9.2.4.3.\rTargeting and Disrupting the Tumor Vasculature.The tumor vasculature has recently been indicated as an important target ...	174
9.2.4.4.\rInducing an Anti-Tumor Immunological Response.The combination of a PS and light (PDT) has previously been shown to induc...	174
9.2.5.\rPCI of Drug-Resistant Cancers	174
9.3.\rFuture Challenges	174
9.3.1.\rFuture Challenges with PCI and Vascular Targeting	175
9.3.2.\rFuture Challenges with PCI and CSC Targeting	175
9.3.3.\rFuture Challenges of Using PCI to Harness the Immune System	176
9.4.\rConclusion	176
References	176
Chapter 10 - Photochemical Internalization – A Technology for Intracellular Drug Delivery: The Bleomycin Case	181
10.1.\rBackground	183
10.2.\rThe BLM Case	183
10.2.1.\rBLM Structure and Function	184
10.2.2.\rCellular Uptake Mechanisms of BLM	187
10.2.3.\rPCI for Enhancing the Therapeutic Effects of BLM	188
10.2.4.\rBLM – Adverse Effects	193
10.3.\rConclusions	193
References	194
Chapter 11 - Mind the Gap: 3D Models in Photodynamic Therapy	197
11.1.\rIntroduction	199
11.2.\r3D Models for Evaluating PDT Dose Parameters	200
11.2.1.\rPS Delivery and Distribution	200
11.2.2.\rHypoxia and Oxygen Gradients	202
11.2.3.\rPhotobleaching	203
11.3.\r3D Models to Evaluate PDT Efficacy	204
11.3.1.\rPDT Response in 2D Versus 3D Models	204
11.3.2.\rPDT-Based Combinations in 3D Models	207
11.4.\rAnalysis Framework to Quantify PDT Response	209
11.4.1.\rAnalysis Techniques	210
11.4.2.\rTreatment Response Metrics	211
11.5.\rFuture Directions and Perspectives	214
Acknowledgements	216
References	217
Chapter 12 - Instrumentation for Clinical Photodynamic Therapy and Photodynamic Diagnosis	223
12.1.\rIntroduction	225
12.2.\rPDT Instrumentation	226
12.2.1.\rLight Sources and Delivery	226
12.2.2.\rTreatment Planning and Dosimetry	229
12.2.3.\rTreatment Response Monitoring	232
12.3.\rPDD Instrumentation	234
12.3.1.\rWide-Field Fluorescence Instruments	235
12.3.2.\rEndoscopic Fluorescence Imaging Instruments	235
12.3.3.\rPoint Fluorescence Instruments	237
12.3.4.\rMulti/Hyper-Spectral and Quantitative FDD Instrumentation	237
12.3.5.\rQuantitative Fluorescence Imaging	238
12.3.6.\rMultimodal PDD Instrumentation	238
12.3.7.\rInstrumentation for NP-Enabled Diagnostics	239
12.4.\rConclusions	240
References	241
Chapter 13 - Optical Guidance for Therapeutic Interventions	245
13.1.\rIntroduction	247
13.2.\rOptical Guidance in PDT	247
13.3.\rBeyond Photodynamics	248
13.4.\rBeyond PDT and Surgical Guidance	250
13.5.\rBeyond Cancer Guidance	253
13.6.\rNanoparticles in Optical-Guided Interventions	253
13.7.\rConclusions	254
Acknowledgements	254
References	255
Chapter 14 - Photodynamic Therapy Within the Global Treatment of Thoracic Cancers	259
14.1.\rIntroduction	261
14.2.\rHistorical Review	261
14.2.1.\rSurgery	261
14.2.2.\rRadiotherapy	262
14.2.3.\rChemotherapy	262
14.3.\rReview of Photodynamic Therapy in Thoracic Cancers	262
14.3.1.\rSources of Material for the Review	263
14.3.2.\rMethods	263
14.4.\rResults of the Review	264
14.4.1.\rPDT for Lung Cancer	264
14.4.1.1.\rFacts and Figures on Lung Cancer.Surgical resection is the primary treatment for lung cancer, which claims near 1.4 mil...	264
14.4.1.2.\rPDT as MonoModalilty Therapy vs. PDT as MultiModality Therapy in Lung Cancer.Table 14.2 shows the results of our review...	266
14.4.2.\rCancer of the Oesophagus	268
14.4.2.1.\rFacts and Figures.Cancer of the oesophagus affects over 450000 individuals per annum in the world, and despite consider...	268
14.4.2.2.\r“Standard Methods” of Treatment for Oesophageal Cancer.In most countries of the world, surgery, radiotherapy and chemot...	268
14.4.2.3.\rRole of PDT in Oesophageal Cancer: MonMT vs. MulMT	269
14.5.\rMalignant Pleural Mesothelioma	271
14.5.1.\rStandard Treatment for MPM	271
14.6.\rConclusions	273
References	273
Chapter 15 - Methyl-Aminolevulinate/Aminolevulinic Acid Photodynamic Therapy: State of the Art in Dermatology and Possible Developments	279
15.1.\rIntroduction	281
15.2.\rApproved Oncological Indications	281
15.2.1.\rActinic Keratosis	282
15.2.2.\rBasal Cell Carcinoma	283
15.2.3.\rBowen’s Disease	283
15.3.\rOff-Label Indications	283
15.4.\rSkin Cancers Other Than AK, BCC and BD	284
15.5.\rDiseases of the Pilosebaceous Unit	284
15.6.\rMiscellaneous Inflammatory Skin Diseases	284
15.7.\rCutaneous Infections	284
15.8.\rConclusions	285
References	285
Chapter 16 - Photodynamic Therapy and Schizophrenia	289
16.1.\rIntroduction	291
16.2.\rHistorical Perspective	291
16.3.\rSymptom 1: Caught Between Chairs	291
16.4.\rSymptom 2: The Generation Gap	292
16.5.\rSymptom 3: On Not Being a “Business Case”	292
16.6.\rSymptom 4: Bedside and the Ivory Tower	293
16.7.\rSymptom 5: What to License	293
16.8.\rSymptom 6: Persistent Misperception of a Disease	294
16.9.\rSymptom 7: “Vicious Cirulitis”	294
16.10.\rSymptom 8: Short Sightedness 1	294
16.11.\rSymptom 9: Short Sightedness 2	295
16.12.\rConclusions	295
References	296
Chapter 17 - Photodynamic Therapy in Aesthetic Dermatology	299
17.1.\rIntroduction	301
17.2.\rSigns of Skin Aging	301
17.3.\rSkin Rejuvenation Following PDT	302
17.4.\rIPL-PDT	302
17.5.\rPDT with Blue Light	304
17.6.\rPDT with Red Light	304
Conflict of Interest	305
References	307
Chapter 18 - Perspectives of Non-Methyl-Aminolevulinate/Aminolevulinic Acid Photodynamic Therapy in Dermatology	309
18.1.\rIntroduction	311
18.2.\rHematoporphyrin Derivative	311
18.3.\rVerteporfin	313
18.4.\rTemoporfin	313
18.5.\rRostaporfin	314
18.6.\rMeso-Tetraphenylporphinesulfonate Tetrasodium Salt	315
18.7.\rTalaporfin	315
18.8.\rPhthalocyanine Pc 4	315
18.9.\rHypericin	316
18.10.\rIndocyanine Green	316
18.11.\rAdditional Indications	316
18.12.\rConclusion	317
References	318
Chapter 19 - Pre-Clinical Models for Glioma Photodynamic Therapy	321
19.1.\rIntroduction	323
19.2.\rPDT Response Definition	324
19.2.1.\rPDT Dose: Definition and Dose-Quantifying Models	325
19.2.2.\rQuantifying the PDT Dose In vivo for Tissues in the Murine Cranial Cavity	328
19.3.\rCell Lines and In vivo Models	331
19.3.1.\rTechniques for PDT Glioma Therapies Demonstrated in Preclinical Models	336
19.3.2.\rQuantification of Response Post-PDT	337
19.4.\rConclusions	343
References	345
Chapter 20 - Photodynamic Medicine in Neurosurgery: Biochemical, Technical and Clinical Aspects	353
20.1.\rIntroduction	355
20.2.\rPhotosensitisers	355
20.2.1.\rPorphyrin Metabolism and Accumulation in Malignant Glioma Cells	357
20.2.2.\rThe Amount of Intracellular PpIX Increases Exponentially with Malignancy	362
20.3.\rPDT Mechanisms	362
20.4.\rPDT and Normal Brain	363
20.4.1.\rEffect of PDT on Normal Brain	363
20.4.2.\rSelectivity of Phototoxicity	363
20.5.\rImmunology	363
20.5.1.\rGlioma Cancer Stem Cells	364
20.5.2.\rImmune Stimulation	365
20.6.\rOptical Parameters of Brain (Tumour) Tissue	365
20.7.\rPhysics and Instrumentation	365
20.7.1.\rGeneral Remarks Regarding Physics and Instrumentation	365
20.7.2.\rRadial Diffuser	366
20.7.3.\rTreatment Planning for Interstitial 5-ALA-Based PDT	366
20.7.4.\rPost-Surgical PDT	367
20.7.5.\rIntraoperative Integral Irradiation	368
20.7.6.\rIntra-Operative Interstitial PDT	368
20.7.7.\rStereotactic Interstitial PDT	369
20.7.8.\rIrradiation and Intraoperative Measurements	369
20.7.9.\rFractionation	370
20.7.10.\rMetronomic Irradiation	375
20.8.\rMethods and Patients	376
20.8.1.\rMethods and Patients	376
20.8.2.\rAnaesthesia and Oxygen Breathing	376
20.9.\rPDD and FGR	377
20.9.1.\rTechniques	377
20.9.2.\rClinical Aspects	377
20.9.2.1.\r5-ALA-FGR Gross Total Resection.Gross total resection (GTR) was defined in most studies as the absence of contrast enha...	379
20.9.2.2.\r5-ALA-FGR PFS.PFS should always be considered the primary endpoint of any study of HGG treatment. Three studies reporte...	379
20.9.2.3.\r5-ALA-FGR Overall Survival.Overall survival in HGG is an inappropriate primary endpoint because patients and surgeons f...	379
20.9.2.4.\r5-ALA-FGR Specificity.Specificity was defined as the percentage of specimens that were fluorescence negative and contai...	379
20.9.2.5.\r5-ALA-FGR Sensitivity.Sensitivity was defined as the percentage of specimens of HGG that fluoresced using 5-ALA-FGR ver...	382
20.10.\rPhotodynamic Therapy	383
20.10.1.\rConclusions	388
20.11.\rInteraction with Adjuvant Therapies (Chemotherapy and Radiation)	388
20.12.\rDiscussion	389
20.12.1.\rClinical Considerations	389
20.12.2.\rFGR	391
20.12.3.\rLight Dosimetry: Technical Aspects	392
20.13.\rConclusion	394
Acknowledgements	394
References	394
Chapter 21 - Present Status of Photodynamic Therapy for Lung Cancer in Japan	405
21.1.\rIntroduction	407
21.2.\rIndications of PDT for Lung Cancer	408
21.3.\rPDT Using Porfimer Sodium and Excimer-Dye Laser for ESLC	408
21.4.\rPDT Using Talaporfin Sodium and Diode Lasers for ESLC	409
21.4.1.\rDevelopment of Talaporfin Sodium	409
21.4.2.\rDevelopment of the Diode Laser System	410
21.4.3.\rPreclinical Study	412
21.4.4.\rPhase I Clinical Study	412
21.4.5.\rPhase II Clinical Study	413
21.5.\rEvaluation of the Accuracy of PDT	418
21.6.\rPerspectives of PDT for Lung Cancer	419
References	419
Chapter 22 - Contrast-Enhanced Imaging of Photodynamic Therapy in Pancreatic Cancer: From Mouse to Man	421
22.1.\rIntroduction	423
22.2.\rMouse: Preclinical Studies	425
22.2.1.\rDirect Measurement of Verteporfin Uptake in Orthotopic Xenograft Tumors with Fluorescence Imaging	425
22.2.2.\rIndirect Measurement of Verteporfin Uptake Correlates with MRI Contrast in Orthotopic Mouse Tumors	426
22.2.3.\rImaging Verteporfin PDT Outcomes in the Mouse	427
22.3.\rRabbit: Preclinical Studies	430
22.4.\rHuman: CT Imaging Predicts Necrotic Volume in PDT of PaC	431
22.4.1.\rVERTPAC-01 Clinical Study Details	433
22.4.2.\rCT-Derived Venous Blood Content Inversely Correlates with Dose-Normalized Necrotic Volume: An Empirical Approach to Dosim...	433
22.4.3.\rTowards Spatially Resolved Treatment Planning Using CT Imaging and Light Propagation Modeling: Can a Radiation Therapy-Li...	435
22.4.4.\rClinical Experience Summary	436
22.5.\rConclusions and Future Initiatives	436
Acknowledgements	437
References	437
Chapter 23 - Photodynamic Therapy in Gastroenterology	441
23.1.\rIntroduction	443
23.2.\rPalliative PDT for Cholangiocarcinoma	443
23.3.\rCurative PDT for Superficial (Early) Esophageal Cancer	444
23.4.\rSevere Dysplasia in Barrett’s Esophagus	445
23.5.\rConclusion	446
References	446
Chapter 24 - Head and Neck Photodynamic Therapy	449
24.1.\rIntroduction	451
24.2.\rSafety Studies	451
24.3.\rDrugs Used in Head and Neck PDT	452
24.4.\rDevelopment of Lasers for Head and Neck Cancer Treatment	453
24.5.\rClinical Studies	453
24.5.1.\rPrimary Squamous Cell Carcinoma of the Head and Neck	453
24.5.2.\rAdvanced Squamous Cell Carcinoma of the Head and Neck	454
24.6.\rAdjunctive Intra-Operative PDT	455
24.7.\rComplications	455
24.8.\rOther Oncological Applications	456
24.9.\rNon-Oncological Applications	456
24.10.\rNew Drugs	457
References	458
Chapter 25 - Vascular-Targeted Photodynamic Therapy in Prostate Cancer: From Bench to Clinic	461
25.1.\rIntroduction	463
25.1.1.\rPDT and VTP: Mechanisms of Action	463
25.1.2.\rRecent Paradigm Shifts in Cancer Management Have Provided New Opportunities for PDT	465
25.2.\rPathophysiology and Standard of Care in Managing Localized Prostate Cancer (LPCa)	466
25.2.1.\rPathophysiology	466
25.2.2.\rStandard of Care in the Management of LPCa at Early to Intermediate Stages	467
25.3.\rEarly Attempts to Treat LPCa by PDT	468
25.3.1.\rPDT and VTP Applications Aiming at Whole-Gland Ablation	468
25.3.2.\rThe Dilemma of Overtreatment Versus No Treatment of Early-Stage, Low-Risk PCa	469
25.4.\rFocal Ablation of LPCa Tumors at the Early Stages: a New Emerging Approach	470
25.4.1.\rIndex Lesion (IL) Tumors in Prostate As a Treatment Target	470
25.4.2.\rApplication of VTP As a Local Treatment Modality for PCa and the Replacement of Tookad® with Tookad® Soluble	470
25.4.3.\rWST11 VTP Treatment of Tumors in the Prostate: Hemi-Ablation Rather Than Ablation of the IL Only	471
25.4.3.1.\rTreatment Planning and Execution.In a recent publication, Azzouzi et al. provided a detailed description of the standar...	472
25.4.3.3.\rPhase III Clinical Trial Results in the First Approval for Use of Tookad® Soluble VTP.Forty seven in eleven European co...	476
25.5.\rNew Clinical Indications for WST11 VTP	477
25.6.\rConclusion	477
Acknowledgements	477
References	478
Chapter 26 - Photodynamic Therapy in Gynaecology: The Long Way from Bench to Bedside—Photodynamic Therapy for Cervical Dysplasia	481
26.1.\rPhotodynamic Therapy for Cervical Dysplasia	483
26.1.1.\rHuman Papillomavirus Infection, Cervical Intraepithelial Neoplasia and Cervical Cancer	483
26.1.2.\rStandard Treatment of CIN: Conisation	484
26.1.3.\rPhotodynamic Diagnosis of CIN	484
26.1.4.\rPDT of CIN	485
26.1.5.\rConclusion	493
26.2.\rPDD and PDT in Ovarian Cancer	494
26.2.1.\rApplications of PDD	494
26.2.2.\rApplication of PDT	495
26.2.3.\rConclusion	496
References	496
Chapter 27 - The New Possibilities of Autofluorescence Diagnosis in Clinical Practice	503
27.1.\rIntroduction	505
27.2.\rThe Role of Image Processing in AFI	505
27.3.\rClinical Utility of Diagnosis with the Use of AFI	507
27.4.\rAims of Autofluorescence Detection in the Clinic	509
27.5.\rClinical Indications for Autofluorescence Diagnosis	510
References	513
Chapter 28 - Antimicrobial Photodynamic Therapy: A Decade of Development and Clinical Study	519
28.1.\rIntroduction	521
28.1.1.\rAntimicrobial Photodynamics	521
28.1.2.\rMethylene Blue	523
28.1.3.\rAnti-Inflammatory Effects	524
28.2.\rClinical Development	525
28.2.1.\rApplication: Chronic Adult Periodontitis	525
28.2.1.1.\rEffect on CRP.A clinical study of the Periowave photo-disinfection system in 28 systemically healthy patients demonstra...	526
28.2.1.2.\rEffect on Host Cytokines.Periowave aPDT was demonstrated to directly inactivate pro-inflammatory cytokines35 in a well-...	526
28.2.1.3.\rEffects on Innate Immunity (aPDT “Vaccination”).In an important and recent development building upon similar observatio...	527
28.2.1.4.\rClinical Outcomes.aPDT may be deployed as a clinical adjunct to mechanical debridement (scaling and root planing) or as...	528
Case 1 (Provided by J. Andary, DDS)	530
Case 2 (Provided by L. Carlson, RDH)	531
Case 3 (Provided by C. Fairfield, RDH)	531
Case 4 (Provided by V. Benhamou, DDS)	531
Case 5 (Provided by V. Benhamou, DDS)	532
Case 6: Oral Lichen Planus (Provided by L. Carlson, RDH)	533
28.2.2.\rSummary	534
28.3.\rApplication: Anterior Nares Decolonization	535
28.3.1.\rClinical Practice	537
28.3.2.\rHistorical Control Study	538
28.4.\rApplication: Chronic Rhinosinusitis	540
28.4.1.\rClinical Practice	541
28.4.1.1.\rRandomized Controlled Study.A randomized controlled study was designed in order to test the effectiveness of aPDT in 47...	543
28.5.\rConclusion	545
References	546
Chapter 29 - Antimicrobial Photodynamic Therapy: New Anti-Infectives in the Age of Resistance	549
29.1.\rIntroduction	551
29.2.\rAntimicrobial Photosensitizers	551
29.2.1.\rProperties of an Ideal Photosensitizer for Cancer and for Infection	551
29.2.2.\rImportance of Cationic Charge for Antimicrobial PSs	552
29.2.3.\rType I and Type II Photochemistry	554
29.3.\rResistance and Susceptibility	555
29.3.1.\rBroad-Spectrum Antimicrobials	555
29.3.2.\rPlanktonic Versus Biofilm Growth	556
29.3.3.\rDifferences between species and strains	556
29.4.\rIn vivo Studies	556
29.4.1.\rWounds and Burns	556
29.4.2.\rDental/Oral Infections	557
29.4.3.\rOsteomyelitis	557
29.4.4.\rOtitis Media	558
29.4.5.\rFungal Infections	558
29.4.6.\rLeishmania	558
29.4.7.\rTuberculosis	559
29.5.\rClinical Studies	559
29.5.1.\rDental Infections	559
29.5.1.1.\rPeriodontitis.Periodontitis is accompanied by inflammation of connective tissue in the dental pocket and resorption of ...	560
29.5.1.2 .Peri-Implantitis.Although there are many similarities between peri-implantitis and periodontitis, due to the reduced va...	560
29.5.1.3.\rEndodontics.Root canals are commonly infected by bacteria, the most common of which being the biofilm-forming Enterococ...	561
29.5.1.4.\rWhole-Mouth Disinfection.Curcumin is a natural product isolated from Curcumina longa from which the spice turmeric is o...	561
29.5.2.\rNasal Decontamination	561
29.5.3.\rChronic Sinusitis	562
29.5.4.\rEndotracheal Tubes	562
29.5.5.\rWound and Ulcer Infections	562
29.5.6.\rLeishmaniasis	563
29.5.7.\rFungal Infections	563
29.5.7.1.\rOnychomycosis.Onychomycosis is a very common fungal infection of the nails (particularly the nail plate of toenails). T...	563
29.5.7.2.\rCutaneous Infections.Cutaneous mycoses are often caused by Trichophyton spp. when they are called tinea. Interdigital m...	563
29.5.7.3.\rOral Candidiasis.Denture stomatitis (DS) is an inflammatory lesion of the palatal mucosa under complete or partial remo...	563
29.5.8.\rHelicobacter Pylori Infection	564
29.6.\rFuture Directions	564
29.6.1.\rNanotechnology	564
29.6.2.\rPotentiation by Inorganic Salts	565
29.6.3.\rPotentiation by Efflux Pump Inhibitors (EPI)	565
29.6.4.\rActivation of the Host Immune System	566
29.6.5.\rWearable Light Sources	566
29.7.\rConclusions	567
29.7.1.\rAdvantages	567
29.7.2.\rDisadvantages	567
Acknowledgements	567
References	567
Chapter 30 - Photodynamic Therapy for Vector-Borne Diseases†	573
30.1.\rIntroduction	575
30.2.\rInfectious Diseases: Overall Considerations on Global Climate Change and Health	575
30.3.\rVector-Borne Diseases	576
30.3.1.\rVBDs Caused by Protozoa and Metazoa	579
30.3.2.\rVBDs: PDT and Pathogenic Protozoa and Metazoa	580
30.3.3.\rVBDs: PDT and Arthropod Vector Control	582
30.3.4.\rInvasive Mosquito Species in Europe and Control by PDT	585
30.4.\rConclusions	587
References	587
Chapter 31 - Photodynamic Reactions As a Marker of Cerebral Vascular Diseases	591
31.1.\rIntroduction	593
31.2.\rPatients, Materials and Methods	593
31.3.\rResults	594
31.4.\rDiscussion	594
31.5.\rConclusions	598
References	599
Chapter 32 - Photodynamic Therapy in Clinical Cancer Care	601
32.1.\rBackground	603
32.1.1.\rLinking Brixen to Mainstream Clinical Cancer Care	603
32.1.2.\rLinking PDT Enthusiasts to Cancer Research Funders	603
32.2.\rThe London Workshop—The Future of PDT (July 17, 2014)	605
32.2.1.\rIntroduction and Aims	605
32.2.1.1.\rIntroduction by the Chairman.The meeting was chaired by Professor Peter Johnson (Chief Clinician, CRUK) and Professor M...	605
32.2.1.2.\rCurrent Status of PDT—Professor Laurence Lovat.The key strengths of PDT are the nature of the biological effect (differ...	605
32.2.1.3.\rPatient Focus—Professor George Smith.Professor George Smith is an eminent emeritus professor of materials at Oxford Uni...	605
32.2.1.4.\rStructure of Workshop.The remainder of the morning session was devoted to a review of PDT across oncology	606
32.2.2.\rPDT Across the Specialities	606
32.2.2.1.\rSkin Cancer and Pre-Cancer: Dr John Lear.Skin cancers and pre-cancers are very common. Almost everyone in Australia ove...	606
32.2.2.2.\rIntraepithelial Neoplasia (Pre-Cancer): Dr John Lear.Intraepithelial neoplasia (pre-cancer) at muco-cutaneous junctions...	607
32.2.2.3.\rHead and Neck Cancer—Mr Colin Hopper.There is a substantial body of published work on PDT for head and neck cancer, par...	608
32.2.2.4.\rLung Cancer—Professor Sam Janes.PDT using porfimer sodium (Photofrin) is approved for the treatment of early lung cance...	610
32.2.2.5.\rOesophageal Cancer—Professor Laurence Lovat.Most recent interest in oesophageal PDT has been in the treatment of high-g...	610
32.2.2.6.\rBladder Cancer—Miss Joanne Cresswell.Photodiagnosis (PD) is an approved procedure in the UK for detecting dysplasia (pr...	611
32.2.2.7.\rColorectal Cancer and Liver Metastases—Professor David Jayne.Several trials have been undertaken on liver metastases,33...	612
32.2.2.8.\rProstate Cancer—Professor Mark Emberton.Focal therapy for localised disease is being tested as a means of avoiding the ...	613
32.2.2.9.\rPancreatic and Biliary Tract Cancer—Professor Stephen Pereira.A meta-analysis of PDT for biliary tract cancer suggested...	613
32.2.2.10.\rBreast Cancer—Professor Mo Keshtgar.Skin metastases from breast cancer have long been a target for PDT, as these lesio...	614
32.2.2.11.\rBone Tumours—Professor Tim Briggs.The first UK PDT centre for musculoskeletal disease is underway at the Royal Nationa...	614
32.2.2.12.\rBrain Tumours—Dr Herbert Stepp.ALA fluorescence-guided surgical resection of glioblastomas is established as a routine...	615
32.2.2.13.\rGynaecological Cancer: Professor Peter Hillemanns.Fluorescence from topical hexyl aminolevulinate (Hexvix) can define ...	615
32.3.\rFuture Developments and General Aspects Considered at the Workshop	616
32.3.1.\rNew Developments—Professor Stephen Bown	616
32.3.1.1.\rPhotochemical Internalisation (PCI).The principle of photosensitiser plus light is used to break down intracellular mem...	616
32.3.1.2.\rTumour Immunology.It has been shown experimentally that the breakdown products of cells killed by PDT can act as a vacc...	616
32.3.1.3.\rBioluminescence-Activated PDT.It has been shown experimentally that light generated chemically (luciferase plus lucifer...	616
32.3.2.\rCommercial Perspectives	616
32.3.2.1.\rPharmaceutical Company Perspectives—Dr Per Walday and Dr Dirk Huttenberger.PCI Biotech (Per Walday) and Apocare Pharma ...	616
32.3.2.2.\rCRUK Drug Development Office Perspective—Dr Paul Jones.There was further reiteration of the significant regulatory hurd...	617
32.3.2.3.\rThe Small Charity Perspective—Mr David Longman (Killing Cancer).David Longman described the work of Killing Cancer and ...	617
32.4.\rClosing Remarks—Professor Peter Johnson and Professor Matt Seymour	617
Acknowledgements	618
References	618
Chapter 33 - Summary and Perspectives	623
Professor Giulio Jori—by Herwig Kostron	627
Remembering Giulio Jori: A True Gentleman and a Scholar—by Chuck Gomer	628
I Met Giulio Jori—by Thierry Patrice	629
Reflections on the Brixen Symposium and Giulio Jori—by Roy Pottier	629
Giulio Jori—by Stephen G. Bown	630
Subject Index	633

Photodynamic Medicine

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