Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice.
We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.
Jin
Z H
ZH
Department of Dermatology, Fukui Medical University, Japan.
Miyoshi
N
N
Ishiguro
K
K
Umemura
S
S
Kawabata
K
K
Yumita
N
N
Sakata
I
I
Takaoka
K
K
Udagawa
T
T
Nakajima
S
S
Tajiri
H
H
Ueda
K
K
Fukuda
M
M
Kumakiri
M
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D005708:Gallium / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use; D011897:Random Allocation; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D014464:Ultrasonic Therapy
C110704:PH-1126; D017319:Photosensitizing Agents; D011166:Porphyrins; C081908:ATX 70; D002734:Chlorophyll; D005708:Gallium