aluminum-tetrasulfophthalocyanine and Carcinoma--Squamous-Cell

The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and head and neck squamous cell carcinoma (HNSCC).. From 1985 to 2015, PubMed/Medline, Google Scholar, EMBASE, and ISI Web of Knowledge were searched using different combinations of the following key words: PDT, oral precancer, leukoplakia, erythroplakia, erythroleukoplakia, verrucous hyperplasia, oral submucous fibrosis, and HNSCC. Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded.. Twenty-six studies were included in the present study. The number of patients ranged from 2 to 147, with a mean age of 50-67 years. The reported numbers of PMDS and HNSCC ranged between 5 and 225. Photosensitizers used were aminolevulinic acid, meta-tetrahydroxyphenylchlorin, Foscan, hematoporphyrin derivatives, Photofrin, Photosan, and chlorine-e6. Laser wavelength, power density, irradiation duration were 585-652 nm, 50-500 mW/cm. PDT is effective in the management of PMDS and HNSCC.

Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Chlorophyllides; Databases, Factual; Dihematoporphyrin Ether; Erythroplasia; Head and Neck Neoplasms; Hematoporphyrins; Humans; Hyperplasia; Indoles; Laser Therapy; Lasers; Leukoplakia; Leukoplakia, Oral; Mesoporphyrins; Oral Submucous Fibrosis; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome

Background Material and Methods Results Conclusions.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Carcinoma, Squamous Cell; Cell Line, Tumor; Female; Head and Neck Neoplasms; HeLa Cells; Humans; Indoles; Isoindoles; Liposomes; Mouth Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Uterine Cervical Neoplasms; Zinc Compounds

A challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb-conjugates with the hydrophobic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AlPcS(4)). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC-bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 425. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of mTHPC-MAb and AlPcS(4)-MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AlPcS(4) (IC(50) > or = 700 nM), MAb-conjugated AlPcS(4) was found to be highly phototoxic in PDT in all 5 cell lines. AlPcS(4)-BIWA 4 was most consistently effective with IC(50) values ranging from 0.06-5.4 nM. mTHPC-MAb conjugates were in general hardly effective. Phototoxicity (log IC(50)) of the AlPcS(4)-MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AlPcS(4)-MAb conjugates in comparison to mTHPC-MAb conjugates for use in PDT.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Division; Head and Neck Neoplasms; Humans; Immunoconjugates; Indoles; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured

The use of monoclonal antibodies (MAbs) directed against tumor-associated antigens for targeting of photosensitizers is an interesting option to improve the selectivity of photodynamic therapy (PDT). Hydrophilic photosensitizers are most suitable for conjugation to MAbs because of their water solubility. The photosensitizer aluminum (III) phthalocyanine tetrasulfonate [AlPc(SO3H)4] has many ideal photochemical properties; however, because of its hydrophilicity, the free form of this sensitizer does not readily reach the critical intracellular target and, therefore, is ineffective in PDT. On the basis of our previous studies, we hypothesized that AlPc(SO3H)4 might be suitable for PDT when coupled to internalizing tumor-selective MAbs. In this study, a reproducible procedure is presented for coupling of AlPc(SO3H)4 to MAbs via the tetra-glycine derivative AlPc(SO2Ngly)4. Conjugation was performed to chimeric MAb (cMAb) U36 and murine MAbs (mMAb) E48 and 425 using a labile ester. Conjugates showed preservation of integrity and immunoreactivity and full stability in serum in vitro. At molar ratios >4, the solubility of the conjugates decreased. Data on the in vitro efficacy of PDT showed that in the chosen experimental setup the internalizing AlPc(SO2Ngly)4-mMAb 425 conjugate was about 7500 times more toxic to A431 cells than the free sensitizer (IC50s, 0.12 nM versus 900 nM). The AlPc(SO2Ngly)4-mMAb 425 conjugate was also more toxic than meta-tetrahydroxyphenylchlorin-mMAb 425 conjugates and free meta-tetrahydroxyphenylchlorin that had been tested previously (M. B. Vrouenraets et al., Cancer Res., 59: 1505-1513, 1999) in the same system (IC50s, 7.3 nm and 2.0 nM, respectively). Biodistribution analysis of AlPc(SO2Ngly)4-125I-labeled cMAb U36 conjugates with different sensitizer:MAb ratios in squamous cell carcinoma-bearing nude mice revealed selective accumulation in the tumor, although to a lesser extent than for the unconjugated 125I-labeled cMAb U36, whereas tumor:blood ratios were similar. These findings indicate that AlPc(SO3H)4 has high potential for use in PDT when coupled to internalizing tumor-selective MAbs.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunoconjugates; Immunotherapy; Indoles; Mice; Mice, Nude; Organometallic Compounds; Photochemotherapy; Quality Control; Radiation-Sensitizing Agents; Reproducibility of Results; Tissue Distribution; Xenograft Model Antitumor Assays

Eighteen random-bred cats with a total of 19 nasal or aural squamous cell carcinomas were treated with photodynamic therapy, using aluminum phthalocyanine tetrasulfonate as the photosensitizer. Cats were irradiated at power densities of 100 mW/cm2 and energy densities of 100 J/cm2. Successful outcome was obtained in 10 tumors after 1 treatment, and 2 more tumors had complete responses after 1 or 2 additional treatments. Treatments were more effective in tumors of stage T2 or earlier. Five tumors had partial responses, and the response of 2 tumors could not be evaluated. The treatment was safe and well tolerated by most cats, although we found that cats should be kept out of sunlight for 2 weeks after treatment.

Topics: Animals; Carcinoma, Squamous Cell; Cat Diseases; Cats; Ear Neoplasms; Ear, External; Female; Indoles; Male; Nose Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Treatment Outcome

The purpose of this study was to examine the effects of photodynamic therapy utilizing aluminum phthalocyanine tetrasulfonate in vitro on several human malignant and normal cell types, with or without hyperthermia. Cells examined included normal skin fibroblasts, HT-1080 fibrosarcoma cells, SCC-25 (squamous cell carcinoma) and malignant melanoma cells. An argon-pumped continuous wave tunable dye laser at 675 nm was used as the light source, hyperthermia groups were heated to 42.5 degrees C, and radioisotope incorporation was used to measure DNA and protein synthesis as toxicity assays. Results showed an energy-dose, and A1PcS-concentration dependent toxicity in all cell lines examined, with moderate selectivity toward malignant cells. Hyperthermia alone was slightly toxic in melanomas and HT-1080 cell lines but had no effect in normal fibroblasts or SCC-25 cells. Hyperthermia synergistically potentiated the effects of PDT in all cell lines, and the combined modality was significantly more toxic in all malignant cell lines compared with normal cells. Thus, addition of hyperthermia to PDT protocols may enhance the efficacy of this treatment modality in vitro.

Topics: Carcinoma, Squamous Cell; Cell Line; Cell Survival; DNA Replication; DNA, Neoplasm; Fibroblasts; Fibrosarcoma; Humans; Hyperthermia, Induced; Indoles; Laser Therapy; Melanoma; Neoplasm Proteins; Organometallic Compounds; Photochemotherapy; Radiation-Sensitizing Agents; Skin; Skin Neoplasms; Tumor Cells, Cultured