1981 Hp 9. 7% Pp 25. 5% YHpD photodynamic therapy PDT PSD-007 HMME Hp HVD Pp 5 Roswell Park Dougherty Photofrin porfimer sodium HpD DHE 90% Photofrin

DOI:10.13480/j.issn1003-9430.2012.05.010 1* 1 2 3 4 2 2 1 5* CBMdisc 1980 ~ 2012 R454. 2 A 1003-9430 2012 05-0278 - 30 Photodynamic Therapy Clinical Research and Application in China LI Li-bo 1 LI Wen-ming 1 XIANG Hong-lei 2 QING Zhong-ping 3 WANG Luo-wei 4 LIN Jin-ran 2 MA Ying 2 HONG Zhen 5* 1. Oncology Department Nanfang Hospital Southern Medical University Guangzhou 510515 China 2. Dermatology Department Hua Shan Hospital 3. Hemangioma Characteristic Professional Subjects of Linyi City Tumor Hopital 4. Gastroenterology Department Changhai Hospital the Second Military Medical University 5. Radiation Oncology Department Colorado University Health Sciences Center ABSTRACT Photodynamic therapy PDT is a non-invasive or minimally-invasive technique combining medicines and devices. Clinical research and application of PDT have been carried out against a large variety of diseases and for a great number of patients in China over the past three decades. To support the study the CBMdisc database was searched and more than 600 clinical literatures on clinical PDT of malignant and non-malignant diseases were retrieved over the period from 1980 to 2011. Data about such issues as disease types case numbers photosensitizers used light sources follow - up dates efficacy and safety were collected analyzed and utilized to understand the history and current status of clinical PDT in China. Technical and clinical issues concerning PDT were discussed. This review will provide health care providers a valuable guidance on clinical PDT. Key words Photodynamic therapy Research Application Malignant disease Non-malignant disease 1. 510515 2. 3. 4. 5. 1964 ~ * 278

1981 Hp 9. 7% Pp 25. 5% YHpD photodynamic therapy PDT PSD-007 HMME Hp HVD Pp 5 Roswell Park Dougherty Photofrin porfimer sodium HpD DHE 90% Photofrin 1993 Photofrin Photofrin Photofrin Photosan Photogem HMME 3 8-1- -8 3-1- / Ⅸ reactive 6 oxygen species ROS 7 8 251 PDT 5- δ- 1-3 ALA Ⅸ Pp Ⅸ ALA hematoporphyrin derivative photodynamic diagnosis HpD 4 PDD 9 ALA Hp - HVD Pp BHpD 2001 630 nm a 630 ~ 650 nm b 650 ~ 680 nm 750 ~ 800 10 40. 7% DHE 20% HVD 14. 1% 279

e6 BPD-MA mthpc CPD4 CDHS801 HpD ZnPcS 2 P 2 1 PDT Tab. 1 Laser types in photodynamic therpy Laser types Wave nm 1 413 Kypton laser 2 3 510. 6 578. 2 Copper bromide laser LED LED Argon ion laser LED Copper vapor laser KTP KTP laser 510. 6 578. 2 488. 0 514. 5 YAG 630 Frequency doubled YAG dye laser 1 KTP 627. 8 Gold vapor laser PDT LP- PDL PDT He-Ne 632. 8 He-Ne laser 863 630 Argon ion pumped dye laser 243 330 ~ 1 660 Diode laser 177 ~ 5 000 Solid-state laser 11 MRI 12 PET 1. 2. 280 532

3. Paget 40 13-52 1984 WHO 32 4. 690 CR 573 83. 04% SR /PR 1 270 nm 89 12. 90% MR + NR 28 4. 05% HpD 221 ALA 655 HMME 31 Photofrin 8 He-Ne CBMdisc He-Ne 2000 1980-2011 ALA PDT 74% 20% 3 ~ 4 h 60 ~ 200 J /cm 2 ALA 8 BCC BCC BCC 1984 SCC 1984 CR 39 40 PDT 1 SR 28 50% 1 MR BHpD 5 mg /kg 6 ~ 72 h 50% 1 NR 120 ~ 150 mw /cm 2 WHO 120 ~ 200 J /cm 2 6 CR 1 100% 1 6 PR 40 ALA HpD > 50% 1 NR 1 PD PpⅨ 25% 30 13 95. 94% PDT PDD ALA /PpⅨ 38 PDT 1. PDT 30 53-78 PDT 9 259 235 Ⅰ 198 Ⅲ 1 Ⅳ 15 PDT 1981 45 1984 CR 128 49. 42% SR 98 281

37. 84% MR 32 12. 36% NR 1 0. 39% 87. 26% 226 /259 PDT 0. 5 cm 48 h 56 1987 1984 12 8 CR 0 SR 12 7 T1N0M0 1 T1N2M0 4 78. 6% 12 /15 0% 11 PDT 37. 5 1 He-Ne 75 PDT 3 1 141 ~ 173 mw /cm 2 HpD 5 mg /kg 48 72 h 251 ~ 314 J /cm 2 15 d HpD2. 5 mg /kg 2 ~ 7 4 33% CR 2 2. 8 67% SR 4 ~ 16 PDT 120 1984 32 71 26 6 YHpD 5 mg /kg 24 48 72 h Ⅳ 1 6 32 800 mw /cm 2 PDT CR 20 62. 5% SR 30 min 1984 10 31. 25% 93. 75% CR105 55. 0% SR66 34. 6% 89. 5% 171 /191 58 YHpD 6 2 ~ 9 5 T1N0M0 130 3 44. 6% 5 CR 1 T3N1M0 2 68 25. 4% PDT 69 16 Ⅰ 10 Ⅱ 6 PSD-007 Photosan 2 mg /kg 48 h 33 23 200 J /cm 2 72 ~ 96 h 10 1 CR12 SR4 CR15 45. 45% SR12 36. 36% MR6 18. 18% 81. 81% 27 /33 PSD-007 YHpD PSD- Photofrin 2 mg /kg 48 h 007 YHpD 64 1 ~ 3 PDT 5 60 63 191 58 68-70 75 62 4 Ⅰ 16 Ⅱ 7 Ⅲ 2 70 10 4 Ⅰ Ⅱ Ⅲ Ⅳ 1 6 100 ~ 150 J /cm 2 200 ~ 72 2006 15 300 J /cm 2 48 h Photofrin PDT 1 ~ 3 15 CR3 SR6 MR1 30 Ⅳ Photofrin 2 mg /kg 48 h PDT 200 ~ 300 J /cm 2 282

3. BHpD 48 HMME86 Photofrin104 Photosan15 PDT YAG He- 53 54 Ne 50 ~ 300 J /cm 2 67 PDT 5 24 h 71 73 74 76 54 4 40 118 1984 35 PDT 1 76. 27% 90 /118 2 31 54. 24% 64 /118 PDT 4 Ⅰ 2 Ⅱ 3 Ⅲ 16 Ⅳ 14 PDT CR9 SR20 MR6 25. 71% 82. 86% 71 28 PDT 5 26 4 1 Photosan 24 h Photofrin 2 mg /kg 2 mg /kg 48 h 50 ~ 100 J /cm 2 24 h 1 200 J /cm 2 Ommaya 8 mg 2 d 4 / 5 1 3 6 1 1 MRI PDT PDT 7. 1% 2 /28 23. 1% 74 6 /26 P < 0. 01 1 PDT 20 CR4 SR12 MR4 79-94 280 273 102 54 117 6 1 84 Photofrin 89. 3% 25 /28 65. 7% 17 /26 10 6 P < 0. 01 2 PDT 67. 9% 4 19 /28 38. 5% 10 /26P < 0. 01 80% PDT PDT PDT 89 HMME PDT 30 48 h HMME 2 mg /kg 100 J /cm 2 30 75 mg 6 28 d 1 5 d 23 d 1 76. 21% 2 58. 07% 79 1 56. 67% 2 42. 27% 1 83. 20 ± 5. 752 76. 20 ± 5. 16 13 PDT 1 71. 20 ± 5. 22 2 283

61. 20 ± 5. 11 P < 0. 05 91 HMME-PDT HMME 5 mg / kg 3-5 h 100 ~ PDT 200 J /cm 2 95 96 PDT 20 95-115 488 374 223 116 HMME 17 8 2 3 4 1 PDT 114 162 Ⅲ 96 Ⅳ 66 326 PDT HpD Photofrin Photosan PDT He-Ne 1984 268 CR97 36. 19% SR130 48. 51% MR32 11. 94% NR9 3. 36% 84. 70% PDT 227 /268 86 92 PDT Photofrin Photofrin Photosan 93 2005 113 Photofrin 28 48 h Photosan 14. 3% 90% 25 / CR4 14. 3% SR20 71. 5% MR4 4 28 15% 4 /28 40 75 100 Photosan2 mg /kg 15 200 J /cm 2 23 15 8 64 42 72 96 h 1 62 44 ~ 2 CR 11 47. 83% SR9 90. 9% 96. 8% 94. 3% 2 PDT PDT 39. 13% MR2 8. 70% 1 1 PDT 3 104 Photofrin Photosan 10 SR7 94 70% MR2 20% 10 8 ALA /PpⅨ 50% 105 Photo- Photosan 10 1 frin ~ 3 1984 70% 284

15% 8 10 9 61 3 878 50% 20% 1996 PDT PDT 15 98 CR10 66. 7% SR3 20% MR + NR2 13. 3% PDT YHpD-PDT 7 + HpD P < 0. 05 15 106 107 HpD Photo- ALA-PDT frin PDT 34 CR 5 14. 71% SR 26 76. 47% MR 3 114 91. 18% PDT Ⅰ 69 Ⅱ 36 Ⅲ 9 ALA P < 0. 01 111 PDT 60 mg /kg 6 h 15 min 3 146 18 CR4 ~ 4 157 22. 22% SR13 72. 22% MR1 5. 56% CR32 57. 1% SR21 37. 5% MR3 5. 4% 250 J /cm 2 70. 5% CR15% 22. 6% 56 5 2 5 142 167 2 3 PDT 347 PDT PsD-007 5 mg /kg 24 48 72 h PDT 350 mw /cm 2 420 J /cm 2 CR66 PDT 5% SR958 72% MR213 16% NR93 164 7% 77% 2007 165 Photofrin PDT BHpD 627. 8 nm 67 2003 ~ PDT 2007 Photofrin 630 nm 95 80 116-199 4757 Photofrin 2 mg /kg 12 ~ 72 h HpD PSD-007 3947 82. 97% Photofrin 424 8. 98% Photosan ALA HMME 59. 7% MR16 23. 9% NR6 9. 0% He-Ne Photofrin CR9 9. 5% SR58 61. 1% MR20 21. 1% NR8 8. 4% PDT PDT 2011 HMME 58 CR5 PDT 82 PDT 153 Photofrin- PDT 124 1994 1982 P < 0. 05 110 YAG 207 123 Photosan PDT 56 45 39 BHpD 5 mg /kg 72 h 200 ~ 139 2000 1991 987 1997 ~ 2003 BHpD 5 mg /kg 200 ~ 400 mw /cm 2 100 ~ 300 J /cm 2 BHpD CR5 7. 5% SR40 8. 6% PR33 56. 9% MR14 24. 1% 1. 2004 200 NR6 10. 3% 285

166 134 162 173 5-Fu 80% 100% 50% 12 PDT PDT PDT PDT 117 71 46 3. 22 Ⅲa 96 Ⅳ 21 Photofrin 2 mg /kg 36 ~ 48 200 J /cm 2 PDT 1997 Stooler 1 1996 2000 4 79 PDT 67. 52% 32 27. 35% 6 130 131 141 5. 13% 185 168 169 48 h HpD 5 mg /kgb MCT PDT - 18 G 48 93. 75% 6 12 18 24 98% 86% 70% 630 nm 1 cm 62% 126 PDT 300 ~ 350 mw 220 J 20 100% 1 1996 34 d 9 30 10 2. 2 30 52 PDT 14 10 6 PDT PDT 1 25 PR 1997 12 SR 13 1 PDT 1 PSD-007 PDT 6 52 WHO CR 1 PR 3 10 ~ 15 d MR 1 NR 1 66% 4 /6 132 2000 70 140 PDT 5 ~ 10 cm 26 11 ~ 15 cm 35 50 15 cm 9 170 1 CR 6 12% SR 22 44% MR 10 20% NR 12 24% 56% 10% 2 2 1 1 2 3 4 5 84% 76% 60% 52% 42% 190 1 11 Photofrin 2 mg /kg 630 nm 12 min Photofrin PDT 5 4 2 PDT 1 0 1 1 ~ 16 cm 17 7 ~ 10 cm 13 28 30 40 1 1 50% 2 8% 3 1 82% 2 50% 3 32% 3 5 18% 48 h ALT AST < 50 U 200 J2 d TBIL 1 ~ 5 CR 1 8. 3% PR 8 66. 7% 17% 3 ~ 4 d 30% MR 1 8. 3% NR 2 16. 7% 3 ~ 5 d 75% PDT PDT 286

4. 5 10% PDT PDT 2007 197 PDT 2 163 1 DSA PDT 1 PDT 5 mg /kg 48 h 100 J /cm 2 3 h 2 19 180 181 PDT 39 ~ 90 70. 3 3. 5 15 8 4 ~ 12 cm 2. 5 ~ 5 mg /kg 48 h PDT 7 ERCP 250 J /cm 2 PDT 2 ~ 5 mg /kg24 48 72 h 250 J /cm 2 5 mm 2 3 20% 12 80% 20 243 d 163 ~ 575 d PDT PDT 6 1 2 92. 3% 76. 9% 12. 0% 66. 7% 42. 3% 0% PDT 182 P < 0. 05 P > 0. 05 7 TBIL 183 6 P < 0. 05 1 PDT Photofrin 2 mg /kg 48 ~ 72 h CA125 CA199 200 ~ 250 J /cm 2 1 P < 0. 05 4 PDT 1 328 ± 75 μmol /L 83 ± 32 μmol / L TURBT PDT 2 50% ~ PDT 60% 1983 PDT PDT 201 PDT 198 199 39 4 cm 2 cm 10 mm 10 mm 7 CA199 25 201-225 800 5. 287

HpD 64. 28% P < 0. 01 224 PDT 212 1992 117 PDT 206 < 1 cm 86 1 ~ 2 103 6 8 1 3 2. 9% 2 ~ 5 15 14. 6% 6 ~ 8 13 12. 3% 30. 1% 1 ~ 2 cm PDT 2 ~ 4 HpD PDD cm 75 > 2 cm 45 ALA PDT PDD 103 86 14 3 220 34 ALA 9 T2 ALA ~ T3 2 ~ 3 h D-LIGHT BHpD3 ~ 5 mg /kg 48 ~ 72 h 500 mw / 31 cm 2 26 5 3 45 ~ 60 J /cm 2 2 1 11 2 48 h HpD 80 ~ 100 J /cm 2 < 2 cm 1 2 6l 2 ~ 4 cm 2 ~ 3 PDD 97. 6% 41 / 3 > 4 cm 6 42 47. 4% 9 /19 221 3 56 ALA PDD 56 155 64 8 83 64 63 98. 4% 83 6l 73. 5% cm 4 cm 26. 5% 78. 1% 50 /64 45. 8% 38 /83 54. 2% ALA PDD 217 1998 218 chlorophyl derivative CPD4 a ALA PDT 32 17 53. 13% 28 PDD 11 39. 29% P > 0. 05 PDT 2003 219 ALA CDHS801 PDD 2006 ALA PDT CDHS801 PDT TURBT 32 2 12. 5% TURBT + 28 2 288

8 11 226 227 PDT VIN PDT Bowens 228 226 227 234 HPV 15 HpD PDT 235 PDT CIN 12 229 ALA-PDT 21 1 98 ~ 2 CIN Ⅰ HPV 5 mg /kg 288 J /cm 2 1 ~ 10% ALA 4 h 635 nm 2 100% 96% 2 1 3 3 6 CIN 71. 4% 15 /21 85. 7% 18 /21 6 12 HPV 81. 0% 17 /21 90. 5% 19 /21 3 HPV 0. 5 ~ 1. 0 cm P < 0. 05 ALA-PDT CIN 1. 1 ~ 1. 3 cm HPV DNA 236 CEF 2 ~ 3 48 h 230 62 5 mg /kg CIN Ⅰ HPV 270 J /cm 2 48 77. 42% 1 1 1. 61% CEF /TAC 1 41 66. 13% ALA-PDT 3 ~ 12 HPV 4 ALA-PDT HPV PDT 231 237 ALA-PDT 7 CIN Ⅱ 238 CIN Ⅲ HPV 2 PDT 3 ~ 5 3 6 9 CIN Ⅱ HPV CIN Ⅲ 4 ~ 5 6 HPV PDT HPV Paget ALA-PDT 232 21 31 52 Paget PDT 25 39 43 48 Paget 1% PDT 233 Paget 13 PDT 289

PDT 255 PSD-007 130 PDT 256 630 239 PDT nm 600 ~ 700 nm PSD-007 11 257 413 nm 240 HMME PDT PSD-007 HpD PDT PWS PDT 1 cm 2 ~ 6 258 PDT PWS 27 11 5 2 35 6 4 2 PDT 259 2001 HMME 2 ~ 3 d BHpD HMME 241 HMME 242 2 ~ 3 d 1 216 1 632 93% 13. 2% 68. 3% 18. 4% BHpD BHpD PSD-007 858 port wine stain PWS HMME 774 3 ~ 7 mg /kg 50 ~ 100 mw /cm 2 90 ~ 540 J /cm 2 PDT 243 1991 244 PDT 9 BHpD PDT 13. 2% 44. 3% 50 36. 2% 6. 3% 0% HMME 6. 7% 3 000 34. 5% 53. 6% 5. 2% 0% 700 2000 296 P < 0. 01 BHpD HMME 2005 238 93. 7% vs 2009 462 245-249 94. 8% BHpD > 70% HpD PSD-007 HMME < 3% < 7% KTP 4 ~ 12 30 ~ 90 d 3 HMME < 50% < 1% < 3% PDT 4 ~ 16 7 ~ 14 d 1 PDT BHpD BHpD HMME 244 PWS 250 PSD-007 532 nm KTP 260 7 HMME 251-253 PSD-007 HMME BHpD PWS PSD-007 5 min PSD-007 532 nm KTP 254 HMME 1 /3 15 min 290

532 nm IPL 555 ~ 990 nm PDL 160 ~ 360 J /cm 2 80 ~ 100 mw /cm 2 585 nm PDT 30 ~ 60 min 3 PWS 1 PSD-007 585 nm PDL HMME-PDT 33. 3% HMME 6. 7% 100% 80% PSD-007 HMME 2 ~ 10 112 PDL 98 PDT 5 PDL HMME PWS 3. 07% 34. 36% PDT 37. 02% 42. 31% PDL 16. 07% 50. 89% PDT 23. 47% 38. 78% 40 PWS Ⅱa PDT PDL PDT 242 PDL PDT PDL 16 ~ 50 90% 18% PDL PDT PDL PDT 266 267 HMME 5 268 PDT PDL mg /kg 20 min 10 PDT KTP Nd YAG 532 nmpws PDL 20 min 80 ~ 100 mw /cm 2 96 ~ 120 J /cm 2 5min 30 min 144 ~ 180 J /cm 2 5 ~ 7 cm8 80% 95% 268 35% vs 20% 45% vs 65% PWS PDT 269 BPD-MA PDT PWS PDL 261 270 BPD-MA 246 HpD PDT PDL VEGF 271 PDT 270 VEGF 272 PDT PDT PWS 246 262 263 AMD CNV AMD 264 265 2006 VPW 18 ~ 30 163 PDL 208 PDT PDL PDT PDT 291

PDT Packer CNV PDT CSC PCV photoradiation therapy PRT CNV Miller ICGA OCT PDT BPD-MA 285 PDT CNV BPD-MA 286 LDL VEGF LDL CNV CNV CNV BPD-MA BPD-MA-PDT VEGF CNV AMD CNV 2000 4 PDT BPD-MA -PDT VEGF PDT AMD CNV 273 CNV -PDT CNV PDT 2 mg /ml 287 3 ml /min PDT 6 mg /m 2 15 min VEGF bevacizumab 689. 3 nm ranibizumab 288-291 CNV 600 mw /cm 2 50 J /cm 2 83 s CNV HPV 274 -PDT HPV 16 18 AMD -PDT CO 2 273-291 HPV 32 ALA-PDT 32 -PDT AMD ALA CNV 275 24 HPV Ⅸ CNV HPV CNV ALA- 276-281 PDT PDT 292-294 ALA-PDT PDT 282-284 PDT PDT 292

ALA He-Ne CO 2 WHO PDT PDT 292-322 CO 2 295 2000 300-303 ALA-PDT HPV 10% ALA 3 h He-Ne 304 305 632. 8 nm 100 mw /cm 2 ALA 100 J /cm 2 18 67 34 1 ~ 6 ALA PDT 6 6. 93% ALA- PDT CO 2 296 ALA 60 PDT 0. 5 1 3 5 10% ALA 5 306 1 3 5 7 h Ⅸ 1 5% 10% ALA Ⅸ 3 h Ⅸ 5h 7 h 3 h 307 CO 2 PDT ALA-PDT ALA 5% ~ 10% 3 ~ 5 h 297 453 308-313 PDT IL-6 IL-12 TNF-α 314 PDT 298 272 287 20% ALA 632. 8 nm He-Ne ALA-PDT ALA-PDT CO 2 315-320 321 322 > 98% > 99% 318 ALA-PDT 45 10. 77% CO 2 33. 33% 10% ALA 4 h 1 ~ 4 PDT 7. 67% 97. 8% 44 /45 3 53. 57% 6. 8% 3 /44 CO 2 14 /111 ALA-PDT ALA HPV CO 2 299 20% ALA 36 2 cm 2 h ALA-PDT HPV HPV DNA 320 2009 11 28 17 0. 5 ALA-PDT 321 cm 5 2 cm HPV PpⅨ 322 20% ALA 3 h ALA /PpⅨ HPV 100 ~ 172 J /cm 2 293

3 d PDT = + 100% 80% ~ 95% ALA PDT 326-338 326 2006 46 5% ALA 3h 633 nm 20 ~ 30 min 10% 126 J /cm 2 6 91. 3% ALA A 323 A 327-329 46% ~ 67% ALA-PDT A A 330 4 80% ~ 90% 70% ~ 89% 30 A 10% ALA 1 ~ 5 h PpⅨ 2 A 3% 5% 10% ALA 3 h PpⅨ ALA PDT ALA 10% ALA-PDT ALA ALA 1. 3 4. 3 5. 1 5. 8 Ⅸ PpⅨ PpⅨ 3 4 5 h 1 h 2 h P < 0. 05 3% 5% 10% ALA 3 h PpⅨ ALA-PDT P > 0. 05 ALA-PDT A 324 325 ALA-PDT ALA-PDT ALA 30 ALA 3% 3h 332 3% ~ 20% 0. 5 ~ 3 h 20 180 5% ~ 30 min 90% 10% 15% 20% ALA Shalita > ALA 90% 75% ~ 89% 1 4 50% ~ 74% 25% ~ 49% 2 1 3 6 < 25% 294 331 ALA

P < 0. 05 6 PDT SRP 79. 55% 88. 37% 95. 24% 97. 73% 60 SRP + 1 PDT SRP + 2 PDT SRP P < 0. 05 ALA PeriowavePDT 0. 01% w /w 670 nm 100 mw ALA-PDT PDT 5 mm 10% 0. 2 ml 10 s 1 min 15% ALA-PDT 2 PDT 1 6 12 ALA-PDT P. g T. f A. a PDT 333 P. g T. f 1 PDT 2 PDT PDT 334 SRP 335 IL-1β MMP-8 E PDT 336 337 343 420 nm 590 nm PDT ALA-PDT 338 PDT 5 mm 13 20% ALA 30 min 420 nm 4 344 20 ALA-PDT PDT ALA-PDT 339 ALA PDT - 8 4 μm 1 min 25 mw /cm 2 GCF GCF-AST 346 sonodynamic therapy SDT PDT 226 227 340 PDT 347 PACT photodynamic antimicrobial chemotherapy 341 342 2008 2 PDT 1 630 nm ZnPC-PL 670 nm P. g 345 P. g Photofrin PDT 1 295

1 PDT 353 8 PDT 242 275 298 301 348-350 PDT PDT HMME 5 mg /kg 2009 8 PDT 360 J /cm 2 PDT PDT PDT 226 227 PSD-007 532 nm 354 PDT PDT 351-243 2007 International Photodynamic Association IPA 11 355 1993 SPIE 1616 1991 10 42 48 49 356 78 102 108 115 International Conference on Photodynamic Therapy and Laser Medicine 246 261 262 357 292 323 20 PDT 3000 358 352 146 149 150 152 157 161 186 222 223 232 PDT 296

8 Ying Gu Huang NY Liang J et al. Clinical study of 1949 cases of port wine stains treated with vascular photodynam- 359 360 ic therapy Gu 's PDT J. Ann Dermatol Venereol 2007 134 241-244. PDT 9. 5- J. 2009 42 368-370. 10. HpD 100 nm 400 ~ 700 nm 10 J. 2005 40 920-923. 11 Huang Z Xu H Meyers AD et al. Photodynamic therapy for solid tumors-potential and technical challenges J. PDT Technol Cancer Res Treat 2008 7 309-320. 8 11 12 Huang Z. PDT J. 2009 39 PDT 676-683. 13. - 47 J. 1983 63 322-325. 14 Wang JB Gao ML Wen S et al. Photodynamic therapy for 50 patients with skin cancers or precancerous lesions J. Chin Med Sci J Engl 1991 6 163-165. 15. GLH 18 J. 1989 10 496-497. 16. 510. 6 nm J. 3. 32 185-186. 1. - 17. J. J. 1991 17 14-1996 7 23-24. 16. 18. 5-2. Bowen J. 1999 8 9-11. J. 2002 33 269-272. J. 2006 15 121-124. 4 Huang Z. Photodynamic therapy in China Over 25 years of unique clinical experience Part One-History and domestic photosensitizers J. Photodiagnosis Photodyn Ther 2006 3 3-10. 5. J. 2001 10b 44-47. 6. 23. 5- HMME J. 1993 2 3- J. 7. 2006 39 137-139. 7. - 24. ALA J. 1993 Bowen J. 2 235-236. 1991 11 191-193. 19. δ- J. 1999 20. J. 2000 27 95-96. 21 XU SZ WANG XL XU Wei et al. Evaluation of photodynamic therapy of skin cancers with δ-aminolaevulinic acid J. Chin Med J Engl 2002 115 1141-1145. 22. ALA J. 2005 19 209-210. 2006 39 420-421. 25. J. 2007 42 917-918. 297

26. 56. 1 J. 43. 5-2007 23 901-902. J. 27. 2010 39 57-59. J. 2007 44. 16 396-397. J. 2010 29 53. 28. 45. 5-6 J. 2008 17 ALA- PDT Bowen J. 248-250 303. 29. δ- 46. J. J. 2011 2008 14 309-311. 30. 47. 5-1 J. 2008 37 686. J. 31. δ- 2011 25 238. Paget 1 J. 2009 20 844-845. 32. 5- paget 13 J. J. 2011 16 404-405. 2009 38 538-539. 33. 5- - J. 2011 46 J. 1231-1232. 2009 37 791-792. 34. 5- J. J. 2011 18 1623-1624. 2009 38 605-606. 35. 5- J. 2011 15 1778-1779. J. 52 Wang XL Wang HW Guo MX et al. Treatment of skin 2009 8 245-246. cancer and pre-cancer using topical ALA-PDT - A single 36. δ-ala-pdt hospital experience J. Photodiagnosis Photodyn Ther Bowen J. 2008 5 127-133. 2009 7 145-146. 53. 37. J. 1985 20 8-11. J. 2009 54. 8 246-247. 104 J. 38. 1987 4 70. J. 2009 2 55. HpD- 41 160-162. J. 1986 21 96-98. J. 2010 25 55-40. ALA HPD 57. J. J. 1988 10 473-2009 29 548-555. 41. 5-58. J. J. 1991 5 34-35. 2010 16 217-219. 42. 5-1994 3 151-154. 39. 56. HpD Paget J. 2009 12 862- J. 863. 1987 22 137-141. 298 2011 959-960. 20 1417-1419. 48. 49. 50. 5-51. 72 475. 59. J. 60. 57

J.. 1990 12 120-122. 61. J. 1993 20 894-896. 137 J. 1992 14 81. 290-292. J. 2001 62. Ar + 6 213-215. 108 J. 1995 82. 14 368-370. J. 2004 20 30-32. 1996 5 134-136. 64. -Ar + J. 84. 1996 15 285-286. J. 65. 2005 25 116-118. J. 1997 12 123-124. 66. J. J. 2006 19 392-393. 2000 5 149-150. 67. 6 J. J. 2003 20 84-85. 2006 6 2209. 68. 87. J. 2005 26 962-963. J. 2006 69. 4 222-224. J. 2005. 88. 20 J. 2007 16 296-63. 83. 191 J. J. 2004 13 75-70. PHOTOFRIN J. 2008 31 25- J. 26. 2005 9 160-161. 40. 72. PHOTOFRIN 5 J. J. 2006 11 2010 15 80-82. 837-839. 73. 1 J. J. 2007 12 158. 74. - 92. 71. J. 2008 24 200-6 J. 2006 12 39-201. 298 340. 76. Photofrin 94. 5- J. 2010 5 1119-1122. J. 77. 2007 23 369-372. J. 2011 20 29-32. 78. ADV-TK /GCV J. J. 1983 10 329-331. 2011 17 1546-1548. 79. 21 J. J. 1984 5 31-37. 1986 2 80-84. 80. 77. 85. 86. 89. 90. 91. 2012 21 6-8. J. 1996 19 183-184. 93. 75. J. 15 J. 2005 43 2008 22 151-152 180. 334-338. 95. 96. 97. 299

J. 1987 9 50-52. 98. 116 Tian ME Qiu SL Ji Q. Preliminary result of hematoporphyrin derivative-laser treatment for 13 cases of J. 1996 9 48. early 99. esophageal carcinoma J. In Kessel D. ed. Methods J. 2003 9 65-66. in porphyrin photosensitization-advances in experimental 100. medicine and biology series 1985 193 21-25. J. 2004 11 117 Jin ML Yang BQ Li R et al. Analysis of haematoporphyrin derivative and laser photodynamic therapy of 247-249. up- 101. per gastrointestinal tumours in 52 cases J. Lasers Med J. Sci 1987 2 51-54. 2004 10 13-16. 102. 1986 3 2-4. J. 2004 21 65. 103. J. 1988 10 197- J. 2005 11 320. 199. 104. 120 Jin ML Yang BQ Zhang W et al. Photodynamic therapy for the treatment of advanced gastrointestinal J. 2005 12 tumours 1798-1799. 105. 121 Jin ML Yang BQ Zhang W et al. Review of photodynamic therapy for gastrointestinal tumours in the past 6 J. 2007 30 51-52. years in China J. J Photochem Photobiol B Biol 106. 1990 7 87-92. J. 122. - 2006 20 31-32 34. 50 J. 1986 13 64-66. 107. 123 Jin ML Yang BQ Zhang W et al. Evaluation of photodynamic therapy in advanced gastrointestinal - 34 cancer J. 2006 15 102-106. 108. J. 124 Jin ML Yang BQ Zhang W et al. Photodynamic therapy for upper gastrointestinal tumours over the past 10 2006 35 2198-2199. 109. years J. Semin Surg Oncol 1994 10 111-113. J. 2008 28 125. 709-711. 110. 126. J. J. 1994 14 195-196. 2008 14 525-527. 111. J. 1995 9 18 J. 2008 17 187-188. 973-975. 112. 1995 15 208-209. J. 129. 2009 32 546-547. J. 113. PHOTOFRIN 1995 22 570-572. J. 2009 130 Zeng CY Yang D Huang P et al. Ultrasound-guided 36 954-956. interventional PDT of liver cancer J. Proc SPIE 114. 1996 2887 68-72. T J. 2011 42 131. B 15-16. 30 J. 1996 5 115. 63-66. 300 J. 2011 30 151-152. 118. J. 119. - J. Lasers Med Sci 1989 4 183-186. J. J Clin Laser Med Surg 1991 9 45-48. J. 1998 3 62. 127. 128. J.

132. 150. J. 1997 4 J. 2005 19 1183-1185. 162-163. 133. Nd YAG J. 2009 33 531-532. 1997 6 109-110. 134. J. 2005 14 131-132. J. 153. J. 1998 7 198-201. 2005 14 270. 135. 154. J. 1999 16 38 J. 2006 222-224. 136. 155. 30 J. J. 1999 8 104. 137 Jin ML Yang BQ Zhang W. A study of photodynamic therapy for local recurrence of gastrointestinal cancers J. Gastrointest Endosc 1999 49 AB114. 138. 35 J. 2006 41 230-231. J. 2000 9 52. 158. 25 139. J. J. 2006 23 1343. 2000 21 68-69. 140. Nd YAG J. 2006 12 2622-2623. J. 160. / 2000 9 54-55. J. 141. 2006 12 1121-1124 1127. 142. 162. J. - 202 J. 2001 10 25-27. 143. 163. 110 J. 2001 21 291-293. J. 2007 31 81-82. 144. 164. 24 J. 2001 J. 2007 13 30-31. 145. 165. J. 2002 8 28-30. J. 146. 82 PDT 2007 12 27-29. J. 2002 17 759-760. 147. J. J. 2011 20 359-365. 2002 19 51-52. 151. J. 152. 148. J. 2007 16 J. 2003 12 54. 292-295. J. 2000 9 146-161. J. 149. 2007 4 51-52. 149. 168. J. - 2004 8 5518-5520. J. 2007 28 413-490. 2006 23 27-30. 156. J. 2006 14 530-532. 157. 114 159. 1 2007 27 441-444. 16 223-227. 166. 167. 301

415. 169. 186. J. 443 446. 170. J. 2010 19 10-12 67. J. 2007 28 90. 171. J. J. 2010 18 158-159. 2008 7 55-56 70. 8 320-322. 173. J. 2010 31 J. 737-739. 2008 28 454-457. 174. 14 J. 2011 9 175. J. 112 J. 2008 20 72-73. 176. J. 2011 13 21. J. 2007 16 357-361. 177. J. J. 2011 24 886-887. 2007 18 27-28. 178. 148 J. 2011 20 J. 2008 17 23-27 179. J. 2011 24 3863-3864. J. 2008 18 1136-1138. 180. 1999 6 384-386. J. 2007 198. 13 283-285. J. 181. 2011 5 120-123. J. 2008 25 199. 317-319. J. 182 Wang LW Li LB Li ZS et al. Self-expandable metal stents and trans-stent light delivery are metal stents and photodynamic therapy compatible J Lasers Surg Med 2008 40 651-659. J. 2007 16 441- J. 2008 59 15-18. 172. J. 2010 19 156- J. 2008 159. 183. 201. - 26 J. J. 1983 4 327-2009 18 88-91. 328. 184. 202. J. 2009 9 J. 1984 5 26 457. 2009 3 75-76. 2009 18 301-304. 187. 188. 30 189. 190. Photofrin 191. 132-134 150. 192. 2011 18 514-516. 193. DCF 194. 195. 354-358 405. 196. 10 197. J. 2011 18 514-516. 200. 3878 12 J. 2004. 8 1204-1207. 328-329. 185. 203. - 117 J. 21 J. 1985 7 302

113-115. 204 Prout Jr GR Lin CW Benson Jr R et al. Photodynamic therapy with hematoporphyrin derivative in the treatment of super cial transitional-cell carcinoma of the bladder J. N Engl J Med 1987 317 1251-1255. 205 Zhou CN Xu BZ Xie JG et al. An ultrastructural study of human bladder cancer treated by photodynamic therapy J. Lasers Med Sci 1988 3 87-92. 207. - 225. 65 J. 17 J. 1989 10 343-345. 208. 226 Qiang YG Zhang XP Li J et al. Photodynamic therapy for malignant and non-malignant diseases clinical in- 37 J. 1990 11 23-25. vestigation and application J. Chin Med J Engl 209. 2006 119 845-857. 210. Health Sci. 2009 2 73-92. 13 J. 1990 11 281. 211. J. 2003 17 J. 1992 14 379-381. 43-44. 212. 117 229. 5- J. 1992 30 415-416. I J. 213. 2011 5 4751-4755. J. 1994 34 10-11. 214. J. J. 2011 18 78-79. 1994 16 458-460. 206. 224. J. 1988 15 176- J. 2009 178. 36 2696-2699. J. 1990 12 75-76. 215. 7 J. J. 1995 22 317-2011 18 40-44 66. 320. 216. J. 2007 4 30-31. J. 233. 1997 19 463-465. J. 2006 217. 15 395-397. J. 234. 1998 18 15-17. J. 2005 27 1048-1050. 218. 235. J. 12 J. 2006 6 1532. 1998 20 69-71. 236. 219. CDHS 801 J. 2007 J. 2003 16 152-154. 26 306-308. J. 2004 25 619-621. 221. 5-56 J. 2006 11 158-160. 222. J. 2008 23 27-28. 223. 5-20 J. 2008 14 55-56. 1991 13 55-57. 227 Huang Z Li LB Wang HW et al. Photodynamic therapy - an update on clinical applications. J Innov Opt 228. PDT 230. 5-231. 232. 237. 220. 5- J. 34 2007 16 362-364. 303

238. 1996 5 201-204. J. 2008 16 581-582. 527. 241 Pu Y Chen W Yu Z. Research progress of Hemoporfin - Part one Preclinical study J. Photodiagnosis Photodyn Ther 2012 9 180-185. 242 Zhao Y Zhou Z Zhou G et al. Efficacy and safety of hemoporfin in photodynamic therapy for port-wine stain a multicenter and open-labeled phase IIa study J. Photodermatol Photoimmunol Photomed 2011 27 17-23. 243 Huang Z. Photodynamic therapy in China Over 25 years of unique clinical experience Part Two - Clinical experience J. Photodiagnosis Photodyn Ther 2006 3 239. PSD-007 J. 1994 1 126-127.. 2011 255 Lin XX Wang W Wu SF et al. Treatment of capillary 31 692-698. vascular malformation port-wine stains with photochemotherapy J. Plast Reconstr Surg 1997 99 1826-240. 45 J. 2006 18 489 1830. 71-84. J. 244. 2008 17 28-31. J. 1991 13 317. 261. 245 Qiu H Gu Y Wang Y Huang N. Twenty years of J. 1999 5 88- clinical experience with a new modality of vascular-targeted photodynamic therapy for port wine stains J. Der- 262. 91. matol Surg. 2011 37 1603-10. J.. 2005 6 188-189. 246 Yuan KH Gao JH Huang Z. Adverse effects associated with photodynamic therapy PDT of port-wine stain J. 263. PWS birthmarks J. Photodiagnosis Photodyn Ther. 2008 5 35-36. 2012 9 doi 10. 1016 /j. pdpdt. 2012. 03. 007 264. 247. J. J. 2000 21 65-66. 2011 34 779-780. 248. 265. 238 J. J. 2005 3 101-107. 249. 266 Yuan KH Li Q Yu WL et al. Comparison of photodynamic therapy and pulsed dye laser in patients with port 462 J. 2009 18 1146-1147. wine stain birthmarks A retrospective analysis J. 250. Photodiagnosis Photodyn Ther 2008 5 50-57. 40 J. 267. 1992 1 6-10. J. 251. KTP /532 2009 38 126-128. J. 1993 2 154-156. 254. 38 256. - J. 1998 14 163-165. 257. J. 2000 9 168-170. 258. J. 1995 4 151-154. 259. 1216 J. 2001 10 2 86-89. 260. 2006 15 319-322. 268. 252. J. 2006 50 J. 26 465-466 472. 1994 3 215-217. 269. 585 nm 253. J. J. 2009 20 731-733. 304

270. 285. J. 2010 43 J. 67-68. 2011 27 506-509. 271. 286. J. J. 2004 20 127-129. 2011 20 63-64. 272 Wang XL Wang HW Yuan KH et al. Combination of photodynamic therapy and immunomodulation for skin diseases-update of clinical aspects J. Photochem Photobiol Sci 2011 10 704-711. 273 Lam S. J J. 1999 1 115. 2007 23 13-16. 274. 289. J. 2000 Bevacizumab 16 213-216. 275. 2008 24 164-167. 290. PDT AVASTIN J. 2007 43 198- CNV J. 205. 2010 28 1009-1011. 276 Lam DS Chan WM Liu DT et al. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularisation of pathologic myopia in Chinese eyes a prospective series of 1 and 2 year follow up J. Br J Ophthalmol 2004 88 1315-1319. 277. J. J. 2009 23 54. 2004 20 275-279. 278. J. 2009 8 J. 827-828. 2007 23 9-12. 279. J. J. 2011 25 96-98. 2008 24 220-221. 280. J. J. 2000 14 103-104. 2009 25 279-282. 281. 101 J. J. 2003 32 479. 2010 19 227-232. 282. J. 2006 39 J. 685-688. 2007 7 362-363. 283. J. 2007 40 67-70. J. 2008 48 71-73 284. J. 2008 CSC J. 2009 41 296-300. 9 166-168. 287 Qiang YG Yow CM Huang Z. Combination of photodynamic therapy and immunomodulation current status and future trends J. Med Res Rev 2008 28 632-644. 288. J. 291. Ranibizumab J. 2011 13 84-87. 292. 5-293. 5-294. 5- - 295. δ- 296. δ- 297. 298. 299. 5-300. 5-305

CO2 J. 155. 2006 35 674-675. 316. 5-301 Liang J Lu XN Tang H et al. Evaluation of photodynamic therapy using topical aminolevulinic acid hydro- 10 218-219. J. 2010 chloride in the treatment of condylomata acuminata a 317. comparative randomized clinical trial J. Photodermatol Photoimmunol Photomed. 2009 25 293-297. 2010 J. 9 240-241. 302. ALA-PDT 318. 5- J. 2010 J. 24 1121-1122. 2011 3 359 364. 304. 5-339-343. J 320 Wang HW Zhang LL Miao F et al. Treatment of 2010 24 153-154 161. HPV infection-associated cervical condylomata acumina- 305. ta with 5-aminolevulinic acid-mediated photodynamic J. therapy J. Photochem Photobiol 2012 88 565-569. 2011 25 787-788. 306. 5- J CO 2 J. 2009 23 740 742. 2009 42 802-803. 307. - J. J. 2010 19 2009 23 751-752. 235-238. 308. - 2012 34 17-19. J. 324. 5-2010 19 13-16. J 309. 2010 39 417-419. 222 J. 2010 43 366-367. 310. 5- J. J. 2011 49 90-93. 2009 31 220-221. 311. J. 2008 J. 2011 33 17 1670-1671. 869-870. 312. 5- J. J. 2011 13 1129-1131. 313. ALA J. J. 2011 22 59-2010 19 363-365. 60. 329. 5-314. 5- CO 2 J. 2009 42 78-80. J 330. ALA-PDT 2011 25 785-786. 22 J. 2010 24 315 Liu YX Zheng HY Liu XR. 5-Aminolaevulinic acidphotodynamic therapy for the treatment of cervical condylomata acuminate J. Chin Med Sci J 2009 24 151-306 2010 43 694-697. 303. 5-319 Chen MK Luo DQ Zhou H et al. 5-aminolevulinic CO 2 J. acid-mediated photodynamic therapy on cervical condylomata acuminate J. Photomed Laser Surg 2011 29 321. ALA 322. 5-323. J. 325. 326. 5-327. 5% 5-2009 42 81-84. 328. 5-1107-1110. 331. 5- J.

2009 42 563-565. phthalocyanine as an antimicrobial photosensitizer for pe- 332. riodontitis treatment J. J. Porphyrins phthalocyanines 2011 J. 2010 15 293-299. 43 245-248. 333. 5-2011 4 628-630. J. 348 Li CZ Cheng LF Wang ZQ et al. Photodynamic therapy of esophageal varices experimental studies in ani- 2010 19 223-226. 334. ALA mal veins and first clinical cases J. Endoscopy J. 2003 35 1043-1048. 2010 19 1833-1834. 335. J. J. 2005 22 29-33. 2011 33 862-863. 350 Li CZ Cheng LF Wang ZQ et al. Attempt of photody- 336. namic therapy on esophageal varices J. Lasers Med J 2009 18 1136- Sci. 2009 24 167-71. 1139. 351 Qiu H Mao Y Gu Y et al. Vascular targeted photody- 337. 5- namic therapy for bleeding gastrointestinal mucosal vascular lesions A preliminary study J. J. Photodiagnosis 2011 44 667-668. 338. 352 Li JH. Photodynamic therapy in China J. SPIE Proc 339 photosensitizers in China J. Photodiagnosis Photodyn. 5- Ther 2008 5 285-287. J. 2011 44 75-76. 340. J. therapy J. Technol Cancer Res Treat 2005 4 283-2004 29 703-706. 293. J. 2009 29 359-360. 341. 355. J. 2008 24 740- J. 2007 16 386-389. 743. 356. 5-342. J. IL-1β MMP-8 J. 2010 24 1052-1053. 2008 17 10-14. 343.. 2007 14 62-63. J. 358. 2008 18 20-23. 344. 359. J. J. 2007 16 179-185. 2008 18 94-97. 345. upconverting nanoparticles for imaging and photodynamic J. 2006 therapy of liver cancer cells J. Chem Asian J. 2012 22 368-371. 346 Chen J Chen Z Zheng Y et al. Substituted zinc 347. J. 349. Photodyn Ther 2012 9 109-117. 1993 1616 11-13. 353 Huang Z. An update on the regulatory status of PDT 354 Huang Z. A review of progress in clinical photodynamic 357. J. 2009 23 1462-1463. 360 Zhao Z Han Y Lin C et al. Multifunctional core-shell 7 830-837. 2012-07-19 307