ORIGINAL ARTICLE

Histological Responses of Cutaneous Vascular Lesions Following
Photodynamic Therapy with Talaporfin Sodium:
A Chicken Comb Model
Takafumi Ohshiro, Tatsuo Nakajima, Hisao Ogata and Kazuo Kishi

Department of Plastic and Reconstructive Surgery, School of Medicine, Keio University, Tokyo, Japan(Received for publication on May 29, 2009)(Revised for publication on June 25, 2009)(Accepted for publication on July 16, 2009)

Abstract
Background : Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and iscurrently being used in photodynamic therapy for various malignant tumors in combination
with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is thatthe skin photosensitivity after injection of this agent disappears faster than any other existing
photosensitizers. This study examined the vascular events that occurred postirradiation in thechicken comb as a capillary malformation model after photosensitization with Talaporfin sodium.
Materials and Methods : A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiatedwith a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14
days after photodynamic therapy. For the histological examination, HE, PTAH and Azan
stained sections were analyzed.
Results : All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of thecapillaries in the target area, moderate invasion of inflammatory cells and a slight increase in
the stroma were observed.
Conclusions : In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could bea feasible method to treat dermal hypervascular lesions. (Keio J Med 58 (3) : 176－184, September 2009)

Keywords: photodynamic therapy, Mono-L-aspartyl chlorin e6, Talaporfin sodium, port-wine stains,vascular occlusion

Introduction
Capillary malformations, the so-called port-wine stains(PWS), are a congenital vasculopathy consisting of anabnormal network of capillaries in the upper dermis withan overlying normal epidermis. PWS has no tendency toresolve spontaneously. The flashlamp-pumped pulsed

dye laser (PDL) at a wavelength of 585 nm and a pulse
duration of 0.45 ms has been used for the treatment of
PWS since the 1980s. This treatment is based on a photothermal reaction based on the principle of selective
photothermolysis, first proposed by Anderson and Parrish.1 Since 2000, a long pulse-duration PDL has beendeveloped. This machine emits laser energy at a wave-

Reprint requests to: Takafumi Ohshiro, MD, Deparfment of Plastic and Reconstructive Surgery, School of Medicine, Keio University, 35 Shinanomachi,
Shinjuku-ku, Tokyo 160-8582, Japan, TEL: +81-3-3352-0046, FAX: +81-3-3354-1103, E-mail: ttoo@ohshiro.com
176

Keio J Med 2009; 58 (3): 176－184

length of 585/595 nm and has pulse durations from 0.45
to 40 ms, enabling the treatment of larger diameter vessels and those more deeply located in the skin. Currently
the PDL is the ‘gold standard’ for treatment of PWS
worldwide.2-6 However it is difficult to achieve successful results in deeper and thick lesions, and larger diameter vessels, with multiple treatment sessions being required to obtain good results.
On the contrary, photodynamic therapy (PDT) is an
evolving selective cancer treatment which has been reported as being highly successful for treatment of malignant neoplasms since the 1970s.7-9 PDT has a two step
process. The photosensitizer is injected and allowed tocirculate throughout the body, and is selectively taken up
by the cells in highly mitotic tissues including tumors.
The target tissue is then athermally irradiated with lightat a wavelength specific to the photosensitizer. The
athermal photoactivation of the photosensitizer inducesan oxygen-dependent process that results in the generation of highly cytotoxic reactive oxygen species (ROS)
including singlet oxygen. The release of these reactive
molecules results in damage to both the tumor cells containing the photosensitizer and their microenvironment.
There are several photosensitizers which have presently
passed or are under clinical investigation. Hematoporphyrin derivatives (HpDs) such as Photofrin® (Porfimer
sodium) have been approved for use against gastrointestinal cancer and early lung cancer.10-12
From the early 1990s, in addition to the use of PDT for
tumors, PDT with HpDs (HpDs-PDT) activated with red
or green laser (510-630 nm) has been studied for thetreatment of cutaneous vascular lesions.1 3-1 5 PDT for
PWS is based on a photochemical reaction, and not athermal reaction. HpDs-PDT has not been used worldwide because of the prolonged photosensitivity of theskin of patients who have been treated with HpDs. Patients must avoid direct exposure to sunlight or evenstrong artificial light in the longer visible wavebands for
3 to 4 weeks after PDT.
Mono-L-aspartyl chlorin e6 (Talaporfin sodium, Meijiseika Kaisha Ltd., Tokyo, Japan) is a novel photosensitizer, and is currently being used in PDT for various malignant tumors, activated with a 664 nm laser.
The objective of the present study was to ascertain thefeasibility of PDT with Talaporfin (Talaporfin-PDT) in
the treatment of PWS. The main focus of the study concerned the vascular events that occurred postirradiationin the chicken comb as a capillary malformation model
after sensitization with Talaporfin sodium.
Materials and Methods
Animal Model
The chicken comb was chosen as the model, because
its histoanatomy is analogous to that found in hypervas-

177

cular dermal lesions. Adult male chickens weighing between 1.8-2.1 kg were used. After injection of the photosensitizer, the rest of the experiment, including housingof the animals, was conducted in the dark to avoid photoactivation of the photosensitizer other than by the laser.
Photosensitizer and Laser System
Talaporfin sodium is a hydrophilic compound manufactured by coupling aspartic acid and chlorin, which is
extracted and refined from plant chlorophyll. The drug
was reconstituted as a 5.0 mg/ml solution in physiological saline immediately before administration in order toavoid degradation by light due to photochemical activity.
Talaporfin sodium is maximally activated at 410 nmwith a significantly lesser peak at 664 nm. The 664 nm
laser has been used in PDT. As a laser light delivery system in the present study, an aluminum gallium indium
phosphorus (GaAlInP) diode laser was used, (Panalas
6450, Panasonic Ltd., Osaka, Japan), emitting at 664 nm.
The laser wavelength was set at 664 nm and the output
was variable in the range of 50-500 mW at the fiber tip
in continuous wave mode.
Experimental Procedures
Adult cockerels received a single intravenous bolus injection of Talaporfin sodium 2.5 or 5.0 mg/kg. A 1 cm
diameter area of the comb of each animal was irradiatedwith 664 nm laser light. The total light dose was 25 or 50
J/cm2 at a power density of 127 mW/cm2.
Study 1
The first part of the study was to determine the optimal
time for laser irradiation after injection of the photosensitizer and to determine the optimal laser dosimetry todestroy the comb microvasculature, as the metabolism of
Talaporfin sodium in the chicken model had not been reported. Four cockerels were given intravenous injectionsof Talaporfin sodium at the above-mentioned doses. Immediately and at 30 minutes after injection, the combs
were irradiated with laser light (Fig. 1) at a total dose of
25 or 50 J/cm2, with a power density of 127 mW/cm2.
There were another two controls, one which received
photosensitizer without laser irradiation, and the otherwhich received laser irradiation without the photosensitizer. The irradiated areas were recorded daily with macrophotography for 2 weeks. All chickens were histologically examined at 14 days after PDT.
Study 2The objective of the second part of this study was toanalyze how Talaporfin-PDT injured the microvasculature and affected the connective tissues surrounding the

178

Ohshiro T, et al: PDT with Talaporfin for Cutaneous Vascular Lesions

Fig. 1 Experimental schema.
1: Irradiation area immediately after injection.
2: Irradiation area 30 min after injection.

Fig. 2 Chicken comb (subject no. 4) 14 days after PDT.
1: The area immediately after injection was clearly blanched,equaling the irradiated area.
2: The area 30 min after injection showed no remarkable findings.

Table 1 Results of macroscopic findings in Study 1
SubjectNo.

Doseadministered

Irradiation immediately
after injection

Irradiation 30min
after injection

1
2
3
4
5
6

5 mg/kg
5 mg/kg
2.5 mg/kg
2.5 mg/kg
5 mg/kg
0 mg/kg○:50 J/cm2○:25 J/cm2○:50 J/cm2○:25 J/cm2
×:0 J/cm2
×:25 J/cm2

×:50 J/cm2
×:25 J/cm2
×:50 J/cm2
×:25 J/cm2
×:0 J/cm2
×:50 J/cm2

Blanching was observed only in the area irradiated immediately after injection.
○:Blanching was demonstrated.
× :No change was observed.

destroyed vessels.
Eight cockerels received a single intravenous bolus injection of Talaporfin sodium 2.5 mg/kg, and immediately
after injection a 1 cm diameter area of the comb was irradiated with 664 nm laser light at the same parameters.
Another two control cockerels were used as in Study 1.
The gross changes in the chicken combs were recorded
for 7 days after PDT. Tissue specimens were routinely
processed for histological evaluation. Hematoxylin-eosin(HE), phosphotungstic acid hematoxylin (PTAH), andAzan stained sections were analyzed at 3 and 7 days after PDT to observe the histological changes associatedwith the blanching.
Results
Optimal timing for irradiation
Table 1 shows the results of the macroscopic findings.

From Study 1, blanching was observed only in the area
irradiated immediately after injection (Fig. 2). Figure 3
shows the normal microvasculature of the chicken comb.
The microvasculature under the epidermis consists ofmultiple capillaries lined with flat, elongated endothelial
cells and filled with erythrocytes. Figure 4 shows thehistological changes in the area irradiated immediately
after injection at 14 days after PDT. In the HE stained
sections the normal microvasculature was destroyed but
the overlying epidermis remained intact. However, in thearea 30 min after injection, there were no significantly
different histological findings, as compared with the normal vasculature of the chicken comb. Furthermore thecontrol animals, which received photosensitizer without
irradiation or irradiation without photosensitizer, showed
the normal comb vasculature.
Following both the Talaporfin injections of 2.5 mg/kg
or 5.0 mg/kg, selective destruction of the microvasculature was observed, but no difference was seen in the de-Keio J Med 2009; 58 (3): 176－184

179

Fig. 3 Normal histological findings of the chicken comb.
The microvasculature under the epidermis consists of multiple
capillaries lined with flat, elongated endothelial cells and filledwith erythrocytes.

Fig. 4 Histological findings of an area irradiated immediately
after injection 14 days after PDT (subject No 4) (HE staining, ×100).
Normal microvasculature cannot be seen under a normal intact
epidermis.

Table 2 Results of macroscopic findings in Study 2
SubjectNo.

Doseadministered

Total irradiation dose
25J/cm2

Total irradiation dose
50J/cm2

1
2
3
4
5
6
7
8
9
10

2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
2.5 mg/kg
0 mg/kg

○
○
○
○
○
○
○
○
×:0 J/cm2
×:25 J/cm2

○
○
○
○
◎
○
◎
○
×:0 J/cm2
×:50 J/cm2

All irradiated areas were blanched 7 days after PDT. Superficial epidermal necrosis was observed on the No.5 and No.7 chicken combs
which had been irradiated with 50 J/cm2.
○: Blanching was demonstrated.
◎: Blanching was achieved, but slight Talaporfin-PDT-mediated epithelial injury was observed.
× : No change was observed.

gree of destruction between the two doses of both thedrug and the irradiation. Our study results suggest that atleast a single bolus injection of Talaporfin 2.5 mg/kg activated with 644 nm laser at 25 J/cm 2 is required toachieve selective destruction of the microvasculature.
In this chicken combs model, it is recognized that thedamaged blood vessels will be regenerated and revascularization will occur due to the nature of the comb, so it
may turn out to be impossible to achieve permanent
blanching. From the macroscopic and histological findings in Study 1, the revascularization was not confirmed
until day 14.

The 2 main points shown by Study 1 were that the selective destruction of the microvasculature in the superficial dermis could be achieved with Talaporfin-PDT under a normal intact epidermis, and that irradiation should
be started immediately after administration.
Gross observations
Table 2 shows the results of Study 2. Talaporfin-PDT
could achieve blanching of the chicken combs. Immediately after PDT, all area appeared darkened following laser irradiation at both 25 J/cm2 and 50 J/cm2 (Fig. 5).

180

Ohshiro T, et al: PDT with Talaporfin for Cutaneous Vascular Lesions

Fig. 5 Macroscopic changes immediately after PDT (subject No 3).
The entire area appears darkened. A: 644 nm laser, 25 J/cm2, B:
644 nm laser, 50 J/cm2.

Fig. 6 Macroscopic changes 7 days after PDT (subject No 3).
Blanching is seen in all areas. A: 644 nm laser, 25 J/cm2, B: 644
nm laser, 50 J/cm2.

The darkened phase continued for 3 or 4 days, pronounced blanching appeared in all irradiated areas until
7 days after PDT (Fig. 6).
Macroscopically there were no differences in the degree of blanching at both light doses, but crust formation
due to partial epidermal necrosis appeared in some of the
50 J/cm2 group.

peared in the irradiated area.

Histopathological evaluation
Figure 7 shows the histological findings 3 days after
PDT. In the darkened area, HE and PTAH stained sections showed that the capillaries were filled with thrombus and degeneration of the endothelial cells, whereas
the overlying epidermis was intact. Moderate lymphocytic infiltration was moreover observed around the degenerated vessels (Fig. 7a, b). Azan staining showedslight stromal increase, especially in collagen fibers
around the degenerated vessels (Fig. 7c, d).
Figure 8 shows the histological findings 7 days after
PDT. HE stained sections showed that the capillaries
were destroyed and had disappeared (Fig. 8a). The lumen of the larger caliber capillaries was occluded withfibrin (Fig. 8b). Normal endothelial cells were not seen.
Azan stained sections showed that the stroma under theepithelium had increased in the upper dermis, collagenfibers had increased in number and were arranged irregularly (Fig. 8c, d). In some cases, partial epidermal necrosis was observed in the areas with stronger irradiation.
In the histological sections, normal microvasculature
consisted of microvessels smaller than 120 μm in thechicken combs. 3 days after PDT, the thrombus of thecapillaries were confirmed to the depth of more than1600 μm from the dermoepidermal junction. 7 days after
PDT, the microvasculature was destroyed and had disap-

Discussion
Talaporfin sodium is a second generation photosensitizer that has been shown to be effective in preclinicaland clinical studies including the treatment of various
malignant tumors and age-related macular degeneration.1 6- 2 0 Talaporfin sodium has a strong absorption
peak at 664 nm and produces high yields of triplet oxygen when excited. This absorption peak at the longer visible red wavelength provides deeper penetration of lightinto the target tissue than at shorter wavelengths such as
green or yellow light which have competing chromophores, namely melanin and hemoglobin. A significant
advantage of PDT with Talaporfin sodium is the reduced
duration of skin photosensitivity as compared with otherphotosensitizers such as Photofrin®, one of the wellknown HpDs. Kessel demonstrated that the kinetics ofTalaporfin elimination from plasma is consistent with ahalf life (T1 / 2 β) of approximately 134 hours, which ismuch shorter than the approximately 250 hours of Photofrin®. Talaporfin is eliminated almost twice as rapidly
as Photofrin®.21 We therefore considered the applicationof Talaporfin-PDT for cutaneous vascular disorders.
From our study, the results of Talaporfin-PDT for PWS
using the chicken comb model demonstrated that selective destruction of the superficial dermal microvasculature could be achieved with PDT, leaving the overlying
epidermis intact. This demonstrates the potential efficacy
of Talaporfin-PDT as a novel modality for the treatmentof PWS.
In Study 1, the optimum timing of irradiation after
photosensitization was determined. Blanching was observed only in the area irradiated immediately after in-Keio J Med 2009; 58 (3): 176－184

181

a

b

c

d

Fig. 7 Histological findings at 3 days after Talaporfin-PDT (subject No 4).
A darkened area of the comb is seen following Talaporfin injection 2.5 mg/kg and irradiation with the 644 nm laser at 25 J/cm2.
(a): Capillaries are filled with erythrocytes and the endothelial cells have degenerated, whereas the overlying epidermis is intact (HEstaining ×400).
(b): Capillary lumina are blocked with thrombus (PTAH staining ×400).
(c): Under the intact epidermis, a mild stromal increase, especially of collagen fibers around degenerated vessels, can be observed(Azan staining ×100).
(d): Chicken comb of subject No 9 as control (AZAN staining ×100).

jection. The pharmacokinetics of Talaporfin sodium inthe chicken model are not clear, but it is considered thatthe concentration of the drug in the vascular component
is associated with the selective destruction of the microvasculature. A longer time period after intravenous injection would allow diffusion of the photosensitizer fromthe targeted microvessels into the interstitial components. It is suggested that a minimum interval is necessary for adequate concentration of the photosensitizer tobe distributed in the microvasculature. PDT under condi-

tions of high plasma photosensitizer levels in the targeted
microvessels implies a photodynamic-mediated vascularmechanism of selective destruction.
After Talaporfin-PDT, the irradiated areas changed
from being dark-colored to blanched. During the darkening phase, the capillaries were filled with thrombus andthe endothelial cells had degenerated, but under a normal
and intact epidermis. In the blanching phase, the capillaries were destroyed, and the lumen of the larger caliber
capillaries was occluded with fibrin. Normal endothelialOhshiro T, et al: PDT with Talaporfin for Cutaneous Vascular Lesions

182

a

b

c

d

Fig. 8 Histological findings at 7 days after Talaporfin-PDT (subject No 3).
A blanched area of the comb can be seen following Talaporfin injection 2.5 mg/kg and irradiation with the 644 nm laser at 25 J/cm2.
(a): The capillaries have been destroyed and have disappeared: normal endothelial cells cannot be observed (HE staining ×400).
(b): The lumen of the larger caliber capillaries remains occluded with fibrin (PTAH staining ×400).
(c): The stroma under the epithelium has increased in the upper dermis and an irregular linear arrangement of the increased collagenfibers can be observed (Azan staining ×100).
(d): Chicken comb of subject No 9 as control (AZAN staining ×100).

cells were not seen in the superficial part of the upper
dermis. Several recent reports have concluded that tumor
destruction after PDT using Talaporfin sodium is dependent on vascular damage and blood flow stasis.22-24 McMahon et al. reported that blood flow stasis was the result of platelet aggregation and mechanical obstructionof the flow rather than vessel constriction after Talaporfin-PDT in a tumor model. Our study suggested the samemechanism occurred in a cutaneous vascular model.
Limited local ischemia caused by erythrocyte congestion

and thrombi formation after Talaporfin-PDT leads to thedegeneration of endothelial cells, and the selective destruction of microvasculature can be achieved.
As a result of Talaporfin-PDT, the stroma around themicrovasculature increased slightly in the upper dermis.
Previous reports have not referred to the microenvironment around the target microvasculature after PDT, but
the results of the present study suggest that TalaporfinPDT for PWS could possibly allow selective destructionof the microvasculature, but with minimal injury to theKeio J Med 2009; 58 (3): 176－184

tissues around the target vessels.
In Talaporfin-PDT for PWS in our animal model, theadequate regimen to achieve the destruction of the microvasculature was a single intravenous bolus of Talaporfin 2.5 mg/kg activated with 25 J/cm2 of 644 nm laser
light. When 25 J/cm2 was compared with 50 J/cm2, partial epidermal necrosis was observed in some of the 50
J/cm2 group, suggesting that this dose was too strong.
Although our results indicate that the degree of photodynamic reaction in both epidermis and dermis is dependent on the PDT dose, more research is required to precisely define conditions such as the dosimetry for boththe photosensitizer and light.
PDT is different from a photothermal treatment suchas PDL. Using an athermal photochemical reaction, Talaporfin-PDT was able to selectively destroy the microvasculature in the upper dermis in our chicken comb
model. According to the measurement of the histologicalsections, Talaporfin-PDT could destroy the microvasculature at a depth of more than 1600 μm from the dermoepidermal junction and consisted of microvessels with adiameter of 20-120 μm. Although there are histologicaldifferences between human skin and chicken comb, ourfindings suggest that Talaporfin-PDT has the possibility
to treat the deeper part of dermis. The greater penetration caused by the longer visible red wavelength (644nm > 585/595 nm) would make it ideal for the treatmentof capillary malformations which are more deeply located and consist of microvessels with various diameters.
Furthermore, a clinical trial of Talaporfin-PDT for cutaneous vascular malformation in humans is currently
underway having received permission from the Institutional Review Board of Keio University School of Medicine in 2007.
Conclusions
In conclusion, Talaporfin-PDT effectively achieved theselective destruction of the microvasculature under an
intact and normal epidermis in the chicken comb model.
It is thought that the PDT mechanism resulted in vascular occlusion by thrombosis caused by a photochemical
reaction, but the interaction between vascular endothelial
cells and the photosensitizer has yet to be elucidated.
Further study is warranted to determine the optimum
conditions, namely the optimum dosimetry of both thephotosensitizer and laser irradiation. The results from thepresent study show that photodynamic therapy with Talaporfin sodium may be a feasible method to treat benign
hypervascular dermal lesions in humans.
Acknowledgements
The authors thank Dr. T Ohshiro, S Imai and A Kaneda
for expert assistance with the experimental planning, andDr. M Sakamoto and Dr. T Yamada for their advisory183

comments on the histopathological analysis.
References
1. Anderson RR, Parrish JA: Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science
1983; 220: 524－527
2. Morelli JG, Tan OT, Garden J, Margolis R, Seki Y, Boll J, Carney
JM, Anderson RR, Furumoto H, Parrish JA: Tunable dye laser(577) treatment of port-wine stains. Lasers Surg Med 1986; 6:94－
99
3. Tan OT, Morrison P, Kurban AK: 585nm for the treatment of portwine stains. Plast Reconstr Surg 1990; 86: 1112－1117
4. Dover JS, Arndt KA: New approaches to the treatment of vascularlesions. Lasers Surg Med 2000; 26: 158－163
5. Laube S, Taibjee S, Lanigan S: Treatment of resistant port wine
stains with V Beam pulsed dye laser. Lasers Surg Med 2003; 33:
282－287
6. Bernstein EF, Brown DB: Efficacy of 1.5ms pulse-duration,
585nm, pulsed-dye laser for treating port-wine stains. Lasers Surg
Med 2005; 36: 341－346
7. Dougherty TJ, Kaufmann JE, Goldfarb A, Weishaupt KR, Boyle
D, Mittelman A: Cancer Res 1978; 38: 2628－2635
8. Dougherty TJ, Lawence G, Kaufmann JH, Boyle D, Weishaupt
KR, Goldfarb A: Photoradiation in the treatment of recurrent
breast carcinoma. J Natl Inst 1979; 62: 231－237
9. Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kassel D, Korbelik M, Moan J, Peng Q: Review: Photodynamic therapy. J NatlInst 1998; 90: 889－905
10. Lightdale CJ, Heier SK, Marcon NE, McCoughan JS Jr, Gerdes
H, Overholt BF, Sivak MV Jr, Stiegmann GV, Nava HR: Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd: YAG laser for palliation of esophageal cancer: multicenter randomized trial. Gastrointest Endosc 1995; 42: 507－512
11. Edell ES, CorteseDA: Photodynamic therapy in the managementof early superficial squamous cell carcinoma as an alternative tosurgical resection. Chest 1992; 102: 1319－1322
12. Kato H, Okunaka T, Shimatani H: Photodynamic therapy for earlystage bronchogenic carcinoma. J Clin Laser Med Surg 1996; 14:235－238
13. Orenstein A, Nelson JS, Liaw LH, Kaplan R, Kimel S, Berns
MW: Photochemotherapy of hypervascular dermal lesions: A possible alternative to photothermal therapy. Lasers Surg Med 1990;
10: 334－343
14. Lin X, Wang W, Wu SF, Yang C, Chang TS: Treatment of capillary vascular malformation (Port-Wine Stains) with photochemotherapy. Plast Reconstr Surg 1997; 99: 1826－1830
15. Chang CJ, Sun CH, Liaw LH, Berns MW, Nelson JS: In vitro andin vivo photosensitizing capabilities of 5-ALA versus Photofrin in
vascular endothelial cells. Lasers Surg Med 1999; 24: 178－186
16. Kobayashi W, Liu Q, Nakagawa H, Sasaki H, The B, Matsumiya
T, Yoshida H, Imaizumi T, Satoh K, Kimura H: Photodynamic
therapy with mono-L-aspartyl chlorine e6 can cause necrosis ofsquamous cell carcinoma of tongue: experiment study on an animal model of nude mouse. Oral Oncol 2006; 42: 46－50
17. Mori K, Yoneya S, Anzail K, Kabasawa S, Sodeyama T, Peyman
GA , Moshfeghi DM: Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer:
mono-L-aspartyl chlorine e6. Retina 2001; 21: 499－508
18. Furukawa K, Okunaka T, Tsuchida T, Kawate N, Konaka C, Kato
H: A phaseⅠclinical study of photodynamic therapy for earlystage lung carcinoma using ME2906 and a diode laser system.
Porphyrins 1998; 7: 199－206
19. Kato H, Furukawa K, Sato M, Okunaka T, Kusunoki Y, Kawahara
M, Fukuoka M, Miyazawa T, Yana T, Matsui K, Shiraishi T, Hori-

184

Ohshiro T, et al: PDT with Talaporfin for Cutaneous Vascular Lesions

nouchi H: PhaseⅡclinical study of photodynamic therapy using
mono-L-aspartyl chlorin e6 and diode laser for early superficial
squamous cell carcinoma of the lung. Lung Cancer 2003; 42: 103－111
20. Taber SW, Fingar VH, Coots CT, Wieman TJ: Photodynamic therapy using mono-L-aspartyl chlorine e6 for the treatment of cutaneous disease: a phase 1 clinical study. Clinical Cancer Research
1998; 4: 2741－2746
21. Kessel D: Pharmacokinetics of N-aspartyl chlorin e6 in cancer patients. J Photochem Photobiol B 1997; 39: 81－83
22. Nelson JS, Liaw LH, Oreistein A, Robert WG, Berns M: Mechanism of tomor destruction following photodynamic therapy withhematoporphyrin derivative, chlorin, and phthalocyanine. J NatlInst 1988; 80: 1599－1605
23. McMahon KS, Wieman TJ, Moore PH, Finger VH: Effect of photodynamic therapy using mono-L-aspartyl chlorine e6 on vessel
constriction, vessel leakage and tumor response. Cancer Res 1994;
54: 5370－5374
24. Shibuya H, Aizawa K, Okunaka T, Konaka C, Saito K, Kato H:
Acute microvascular response to photodynamic therapy withmono-L-aspartyl chlorin e6 and a diode laser: observation undermodified operation microscope. J Tokyo Med Univ 1999; 57: 136－144