Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.
HuangZ.A review of progress in clinical photodynamic therapy. Technol Cancer Res Treat4, 283–294 (2005).
2.
SelmanS. H.Photodynamic therapy for prostate cancer: One urologist's perspective. Photodiag Photodyn Ther4, 26–30 (2007).
3.
MullerP. J.WilsonB. C.Photodynamic therapy of brain tumors — a work in progress. Lasers Surg Med38, 384–389 (2006).
4.
HuangZ.Photodynamic therapy in China: 25 years of unique history — Part two: clinical experience. Photodiag Photodyn Ther3, 71–84 (2006).
5.
BielM.Advances in photodynamic therapy for the treatment of head and neck cancers. Lasers Surg Med38, 349–355 (2006).
6.
HautmannH.PichlerJ. P.SteppH.In-vivo kinetics of inhaled 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in bronchial tissue. Respir Res8, 33 (2007).
7.
ArensC.ReussnerD.WoenkhausJ.Indirect fluorescence laryngoscopy in the diagnosis of precancerous and cancerous laryngeal lesions. Eur Arch Otorhinolaryngol264, 621–626 (2007).
MoserJ. G.Definitions and general properties of 2nd & 3rd generation photosensitizers, In: Photodynamic Tumor Therapy – 2nd & 3rd Generation Photosensitizers, pp. 3–8. Ed., Moser, J. G. Harwood Academic Publishers, London (1997).
JankunJ.LilgeL.DouplikA.Optical characteristics of the canine prostate at 665 nm sensitized with tin etiopurpurin dichloride: Need for real-time monitoring of photodynamic therapy. J Urol172, 739–743 (2004).
12.
DuK. L.MickR.BuschT. M.Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer. Lasers Surg Med38, 427–434 (2006).
13.
Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group.Photodynamic therapy of subfoveal choroidal neovascularisation in age-related macular degeneration with verteporfin. Two year results of two randomized clinical trials — TAP report 2. Arch Ophthalmol119, 198–207 (2001).
14.
YuanK. H.LiQ.YuW. L.Comparison of photodynamic therapy and pulsed dye laser in patients with port wine stain birthmarks: A retrospective analysis. Photodiagn Photodyn Ther 5.50–57 (2008).
15.
HuangZ.ChenQ.LuckD.Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer. Lasers Surg Med36, 390–397 (2005).
16.
TrachtenbergJ.BogaardsA.WeersinkR. A.Vascular Targeted Photodynamic Therapy With Palladium-Bacteriopheophorbide Photosensitizer for Recurrent Prostate Cancer Following Definitive Radiation Therapy: Assessment of Safety and Treatment Response. J Urol178, 1974–1979 (2007).
17.
BrandisA.MazorO.NeumarkE.Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: Synthesis, solubility, phototoxicity and the effect of serum proteins. Photochem Photobiol81, 983–993 (2005).
18.
PreiseD.MazorO.KoudinovaN.Bypass of tumor drug resistance by antivascular therapy. Neoplasia5, 475–480 (2003).
19.
WilsonB. C.WeersinkR. A.LilgeL.Fluorescence in Photodynamic Therapy Dosimetry. In: Handbook of Biomedical Fluorescence, pp. 529–561. Eds., MycekM.PogueB. W.. Marcel Dekker, Inc., New York (2003).
20.
TaggR.Asadi-ZeydabadiM.MeyersA. D.Biophotonic and other physical methods for characterizing oral mucosa. Otolaryngol Clin North Am38, 215–240 (2005).
21.
JankunJ.KeckR. W.Skrzypczak-JankunE.LilgeL.SelmanS. H.Diverse optical characteristic of the prostate and light delivery system: Implications for computer modelling of prostatic photodynamic therapy. BJU Int95, 1237–1244 (2005).
22.
WilsonB. C.MullerP. J.YanchJ. C.Instrumentation and light dosimetry for intra-operative photodynamic therapy (PDT) of malignant brain tumours. Phys Med Biol31, 125–133 (1986).
23.
RocheJ. V. E.WhitehurstC.WattP.MooreJ. V.KrasnerN.Photodynamic Therapy (PDT) of Gastrointestinal Tumours: A New Light Delivery System. Lasers Med Sci13, 137–142 (1998).
24.
RendonA.BeckJ. C.LilgeL.Treatment planning using tailored and standard cylindrical light diffusers for photodynamic therapy of the prostate. Phys Med Biol53, 1131–1149 (2008).
25.
NystH. J.vanVeenR. L.TanI. B.Performance of a dedicated light delivery and dosimetry device for photodynamic therapy of nasopharyngeal carcinoma: Phantom and volunteer experiments. Lasers Surg Med39, 647–653 (2007).
26.
WeersinkR. A.BogaardsA.GertnerM.Techniques for delivery and monitoring of TOOKAD (WST09)-mediated photodynamic therapy of the prostate: Clinical experience and practicalities. J Photochem Photobiol B79, 211–222 (2005).
27.
SamkoeK. S.ClancyA. A.KarotkiA.WilsonB. C.CrambD. T.Complete blood vessel occlusion in the chick chorioallantoic membrane using two-photon excitation photodynamic therapy: Implications for treatment of wet age-related macular degeneration. J Biomed Opt12, 034025 (2007).
28.
DrobizhevM.MakarovN. S.StepanenkoY.RebaneA.Near-infrared two-photon absorption in phthalocyanines: Enhancement of lowest gerade-gerade transition by symmetrical electron-accepting substitution. J Chem Phys124, 224701 (2006).
29.
JuzenieneA.JuzenasP.MaL. W.IaniV.MoanJ.Effectiveness of different light sources for 5-aminolevulinic acid photodynamic therapy. Lasers Med Sci19, 139–149 (2004).
30.
MangT. S.Lasers and light sources for PDT: Past, present and future. Photodiag Photodyn Ther1, 43–48 (2004).
31.
SchmidtM. H.BajicD. M.ReichertK. W.II. Light-emitting diodes as a light source for intraoperative photodynamic therapy. Neurosurgery38, 552–556 (1996).
32.
LustigR. A.VoglT. J.FrommD.A multicenter Phase I safety study of intratumoral photoactivation of talaporfin sodium in patients with refractory solid tumors. Cancer98, 1767–1771 (2003).
33.
ChenJ.KeltnerL.ChristophersenJ.New technology for deep light distribution in tissue for phototherapy. Cancer J8, 154–163 (2002).
34.
MartinN. E.HahnS. M.Interstitial photodynamic therapy for prostate cancer: A developing modality. Photodiag Photodyn Ther1, 123–136 (2004).
35.
JohanssonA.AxelssonJ.Andersson-EngelsS.SwartlingJ.Realtime light dosimetry software tools for interstitial photodynamic therapy of the human prostate. Med Phys34, 4309–4321 (2007).
36.
LiJ.ZhuT. C.Determination of in vivo light fluence distribution in a heterogeneous prostate during photodynamic therapy. Phys Med Biol53, 2103–2114 (2008).
37.
HuangZ.ChenQ.ShakilA.Hyperoxygenation enhances the tumor cell killing of Photofrin-mediated photodynamic therapy. Photochem Photobiol78, 496–502 (2003).
38.
ChenQ.HuangZ.ChenH.BeckersJ.HetzelF. W.Improvement of tumor response by manipulation of tumor oxygenation during photodynamic therapy. Photochem Photobiol76, 197–203 (2002).
39.
Vakrat-HagliliY.WeinerL.BrumfeldV.The microenvironment effect on the generation of reactive oxygen species by Pd-bacteriopheophorbide. J Am Chem Soc127, 6487–6497 (2005).
40.
VaupelP.MayerA.Hypoxia in cancer: Significance and impact on clinical outcome. Cancer Metastasis Rev26, 225–239 (2007).
41.
HutchisonG. J.ValentineH. R.LoncasterJ. A.Hypoxiainducible factor 1alpha expression as an intrinsic marker of hypoxia: Correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. Clin Cancer Res10, 8405–8412 (2004).
42.
WoodhamsJ. H.MacrobertA. J.BownS. G.The role of oxygen monitoring during photodynamic therapy and its potential for treatment dosimetry. Photochem Photobiol Sci6, 1246–1256 (2007).
43.
VaupelP.HöckelM.MayerA.Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal9, 1221–1235 (2007).
44.
Tempel-BramiC.PinkasI.ScherzA.SalomonY.Detection of light images by simple tissues as visualized by photosensitized magnetic resonance imaging. PLoS ONE2, e1191 (2007).
45.
GrossS.GileadA.ScherzA.NeemanM.SalomonY.Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI. Nat Med9, 1327–1331 (2003).
46.
SitnikT. M.HamptonJ. A.HendersonB. W.Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. Br J Cancer77, 1386–1394 (1998).
47.
HendersonB. W.BuschT. W.VaughanL. A.Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res60, 525–529 (2000).
48.
CurnowA.HallerJ. C.BownS. G.Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes. Photochem Photbiol B58, 149–155 (2000).
49.
MaierA.AneggU.FellB.Effect of photodynamic therapy in a multimodal approach for advanced carcinoma of the gastroesophageal junction. Lasers Surg Med26, 461–466 (2000).
50.
MaierA.TomaselliF.AneggU.Combined photodynamic therapy and hyperbaric oxygenation in carcinoma of the esophagus and the esophago-gastric junction. Eur J Cardiothorac Surg18, 649–654 (2000).
51.
TomaselliF.MaierA.SankinO.Acute effects of combined photodynamic therapy and hyperbaric oxygenation in lung cancer — a clinical pilot study. Lasers Surg Med28, 399–403 (2001).
52.
TomaselliF.MaierA.PinterH.StranzlH.Smolle-JuttnerF. M.Photodynamic therapy enhanced by hyperbaric oxygen in acute endoluminal palliation of malignant bronchial stenosis (clinical pilot study in 40 patients). Eur J Cardiothorac Surg5, 549–554 (2001).
53.
BislandS. K.LilgeL.LinA.RusnovR.WilsonB. C.Metronomic photodynamic therapy as a new paradigm for photodynamic therapy: Rationale and preclinical evaluation of technical feasibility for treating malignant brain tumors. Photochem Photobiol80, 22–30 (2004).
54.
ChiuS. M.XueL. Y.AzizuddinK.OleinickN. L.Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression. Apoptosis10, 1357–1368 (2005).
55.
GomerC. J.LunaM.FerrarioA.Cellular targets and molecular responses associated with photodynamic therapy. J Clin Laser Med Surg14, 315–321 (1996).
KesselD.ReinersJ. J.Jr. Apoptosis and autophagy after mitochondrial or endoplasmic reticulum photodamage. Photochem Photobiol83, 1024–1028 (2007).
58.
XueL. Y.ChiuS. M.AzizuddinK.JosephS.OleinickN. L.Protection by Bcl-2 against apoptotic but not autophagic cell death after photodynamic therapy. Autophagy4, 125–127 (2008).
59.
StarW. M.MarijnissenJ. P.van den Berg-BlokA. E.ReinholdH. S.Destructive effect of photoradiation on the microcirculation of a rat mammary tumor growing in “sandwich” observation chambers. Prog Clin Biol Res170, 637–645 (1984).
60.
HendersonB. W.FingarV. H.Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor. Cancer Res47, 3110–3114 (1987).
61.
FingarV. H.Vascular effects of photodynamic therapy. J. Clin. Laser Med Surg14, 323–328 (1996).
62.
AbelsC.Targeting of the vascular system of solid tumours by photodynamic therapy (PDT). Photochem Photobiol Sci3, 765–771 (2004).
63.
ChenB.PogueB. W.HoopesP. J.HasanT.Vascular and cellular targeting for photodynamic therapy. Crit Rev Eukaryot Gene Expr16, 279–305 (2006).
64.
HuangZ.ChenQ.LuckD.Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer. Lasers Surg Med36, 390–397 (2005).
65.
KorbelikM.Induction of tumor immunity by photodynamic therapy. J Clin Laser Med Surg14, 329–334 (1996).
66.
CantiG.De SimoneA.KorbelikM.Photodynamic therapy and the immune system in experimental oncology. Photochem Photobiol Sci1, 79–80 (2002).
67.
van DuijnhovenF. H.AalbersR. I. J. M.RoversJ. P.TerpstraO. T.KuppenP. J. K.The immunological consequences of photodynamic treatment of cancer, a literature review. Immunobiol207, 105–113 (2003).
68.
NowisD.StoklosaT.LegatM.The influence of photodynamic therapy on the immune response. Photodiag Photodyn Ther2, 283–298 (2005).
69.
YamamotoN.HommaS.SeryT. W.DonosoT. W.HooberJ. K.Photodynamic immunopotentiation: In vitro activation of macrophages by treatment of mouse peritoneal cells with haematoporphyrin derivative and light. Eur J Cancer27, 467–471 (1991).
70.
KroslG.KorbelikM.DoughertyG. J.Induction of immune cell infiltration into murine SCCVII tumour by photofrin-based photodynamic therapy. Br J Cancer71, 549–555 (1995).
71.
KorbelikM.KroslG.KroslJ.DoughertyG. J.The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy. Cancer Res15, 5647–5652 (1996).
72.
GollnickS. O.EvansS. S.BaumannH.Role of cytokines in photodynamic therapy-induced local and systemic inflammation. Br J Cancer42, 1772–1779 (2003).
Abdel-HadyE. S.Martin-HirschP.Duggan-KeenM.Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. Cancer Res61, 192–196 (2001).
75.
KorbelikM.SunJ.CecicI.SerranoK.Adjuvant treatment for complement activation increases the effectiveness of photodynamic therapy of solid tumors. Photochem Photobiol Sci3, 812–816 (2004).
76.
GollnickS. O.VaughanL.HendersonB. W.Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res62, 1604–1608 (2002).
77.
QiangY. G.YowC. M. N.HuangZ.Combination of photodynamic therapy and immunomodulation — current status and future trends. Med Res Rev28, 632–644 (2008).
78.
StarW. M.Light dosimetryin vivo. Phys Med Biol42, 763–787 (1997).
79.
PattersonM. S.WilsonB. C.Photodynamic therapy, In: The modern technology of radiation oncology, Chap. 23. Ed., VanDyk, J. Medical Physics Publishing, Madison, Wisconsin (1999).
80.
AAPM Report No. 88, Photodynamic therapy dosimetry, AAPM task group report of the general medical physics committee of the science council.Medical Physics Publishing. (2005).
81.
WilsonB. C.PattersonM. S.LilgeL.Implicit and explicit dosimetry in photodynamic theory: A new paradigm. Lasers Med Sci12, 182–199 (1997).
82.
NiedreM. J.SecordA. J.PattersonM. S.WilsonB. C.In vitro tests of the validity of singlet oxygen luminescence measurements as a dose metric in photodynamic therapy. Cancer Res63, 7986–7994 (2003).
83.
DavisS. J.ZhuL.MinhajA.Ultra-senstitive, diode laser based monitor for singlet oxygen. Proc SPIE4952, 140–148 (2003).
84.
YeungW. T.LeeT. Y.Del MaestroR. F.KozakR.BrownT.In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors. J Neurooncol14, 177–187 (1992).
85.
HermanM. A.FrommD.KesselD.Tumor blood-flow changes following protoporphyrin IX-based photodynamic therapy in mice and humans. J Photochem Photobiol52, 99–104 (1999).
86.
BerardV.LecomteR.van LierJ. E.Positron emission tomography imaging of tumor response after photodynamic therapy. J Environ Pathol Toxicol Oncol25, 239–250 (2006).
87.
MolckovskyA.WilsonB. C.Monitoring of cell and tissue responses to photodynamic therapy by electrical impedance spectroscopy. Phys Med Biol46, 983–1002 (2001).
88.
MoriyamaE. H.BislandS. K.LilgeL.WilsonB. C.Bioluminescence imaging of the response of rat gliosarcoma to ALA-PpIX-mediated photodynamic therapy. Photochem Photobiol80, 242–249 (2004).
89.
PogueB. W.PittsJ. D.MycekM. A.In vivo NADH fluorescence monitoring as an assay for cellular damage in photodynamic therapy. Photochem Photobiol74, 817–824 (2001).
90.
DysartJ. S.SinghG.PattersonM. S.Calculation of singlet oxygen dose from photosensitizer fluorescence emission and photobleaching during mTHPC photodynamic therapy of MLL cells. Photochem Photobiol81, 196–205 (2005).
91.
FinlayJ. C.MitraS.PattersonM. S.FosterT. H.Photobleaching kinetics of Photofrin in vivo and in multicell tumor spheroids indicate two simultaneous bleaching mechanisms. Phys Med Biol49, 4837–4860 (2004).
92.
DysartJ. S.PattersonM. S.Photobleaching kinetics, photoproduct formation and dose estimation during ALA induced PpIX PDT of MLL cells under well oxygenated and hypoxic conditions. Photochemical and Photobiological Sciences5, 73–81 (2006).
93.
SvaasandL. O.PotterW. R.The implications of photobleaching for photodynamic therapy, In: Photodynamic therapy: Basic principles and clinical applications, pp, 369–385. Eds., HendersonB.W.DoughertyT.J., Marcel Dekker, New York (1992).
94.
TanI. B.OppelaarH.RuevekampM. C.The importance of in situ light dosimetry for photodynamic therapy of oral cavity tumors. Head Neck21, 434–441 (1999).
95.
EljamelM. S.New light on the brain: The role of photosensitizing agents and laser light in the management of invasive intracranial tumors. Technol Cancer Res Treat2, 303–309 (2003).
FieldingD. I.BuonaccorsiG. A.MacRobertA. J.Fine-needle interstitial photodynamic therapy of the lung parenchyma: Photosensitizer distribution and morphologic effects of treatment. Chest115, 502–510 (1999).
98.
BownS. G.RogowskaA. Z.WhitelawD. E.Photodynamic therapy for cancer of the pancreas. Gut50, 549–557 (2002).
99.
ZhuT. C.FinlayJ. C.HhanS. M.Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy. J Photochem Photobiol B79, 231–241 (2005).
ZhuT. C.HahnS. M.KapatkinA. S.In vivo optical properties of normal canine prostate at 732 nm using motexafin lutetium-mediated photodynamic therapy. Photochem Photobiol77, 81–88 (2003).
FinlayJ. C.ZhuT. C.DimofteA.Interstitial fluorescence spectroscopy in the human prostate during motexafin lutetium-mediated photodynamic therapy. Photochem Photobiol82, 1270–1278 (2006).
104.
WangK. K.MitraS.FosterT. H.A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy. Med Phys34, 282–293 (2007).
105.
ThompsonM. S.JohanssonA.JohanssonT.Clinical system for interstitial photodynamic therapy with combined on-line dosimetry measurements. Appl Opt44, 4023–4031 (2005).
106.
WoodhamsJ. H.MacRobertA. J.NovelliM.BownS. G.Photodynamic therapy with WST09 (Tookad): Quantitative studies in normal colon and transplanted tumours. Int J Cancer118, 477–482 (2006).
107.
BorleF.RaduA.MonnierP.van den BerghH.WagnieresG.Evaluation of the photosensitizer Tookad for photodynamic therapy on the Syrian golden hamster cheek pouch model: Light dose, drug dose and drug light interval effects. Photchem Photbiol78, 377–383 (2003).
108.
HuangZ.ChenQ.DoleK. C.The effect of Tookad-mediated photodynamic ablation of the prostate gland on adjacent tissues — in vivo study in a canine model. Photochem Photobiol Sci6, 1318–1324 (2007).
109.
RendonA.WeersinkR.LotharL.Towards conformal light delivery using tailored cylindrical diffusers: Attainable light dose distributions. Phys Med Biol51, 5967–5975 (2006).
110.
HuangN.ChengG.LiX.Influence of drug-light-interval on photodynamic therapy of port wine stains — Simulation and validation of mathematic models. Photodiag Photodyn Ther5, 120–126 (2008).
111.
XuH.PattersonM. S.Determination of the optical properties of tissue-simulating phantoms from interstitial frequency domain measurements of relative fluence and phase difference. Optics Express14, 6485–6501 (2006).
112.
AllisonR. R.BagnatoV. S.CuencaR.DownieG. H.SibataC. H.The future of photodynamic therapy in oncology. Future Oncol 2.53–71 (2006).
