Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice.
Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.
Megerian
C A
CA
Department of Otolaryngology-Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University, OH 44106.
Zaidi
S I
SI
Sprecher
R C
RC
Setrakian
S
S
Stepnick
D W
DW
Oleinick
N L
NL
Mukhtar
H
H
D000535:Aluminum / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D002455:Cell Division; D017323:Dihematoporphyrin Ether / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D017646:Organosilicon Compounds; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D012821:Silanes; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous; D014316:Tritium; D014407:Tumor Cells, Cultured
D007211:Indoles; D009942:Organometallic Compounds; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D012821:Silanes; D014316:Tritium; C052736:chloroaluminum tetrasulfophthalocyanine; C082854:silicon phthalocyanine; C052464:bis(tri-n-hexylsiloxy)(2,3-naphthalocyaninato)silicon; D017323:Dihematoporphyrin Ether; D000535:Aluminum; D013936:Thymidine