title: Pharmacokinetic, toxicological and phototherapeutic studies of phthalocyanine ZnPcCF3.
abstract: Photodynamic therapy (PDT) is an alternative modality for cancer therapy. It induces neoplasic cells death through photoachievable sensitizers. The aim of this work was to evaluate the pharmacokinetic, toxic and phototherapeutic effects of the phthalocyanine ZnPcCF(3) in a Balb/c mice tumor model. Biodistribution studies were carried out by intraperitoneal injection of 0.2mg/kg ZnPcCF(3). Histological studies and serum biochemical parameters were used to evaluate hepatic and renal toxicity and functionality. After tumor irradiation (210J/cm(2)), an analysis of tumor necrosis degree was used to evaluate the phototherapeutic effects. It was measured at 1, 2, 3 and 4 days after PDT. Vital staining was performed by intraperitoneal injection of 0.35ml 1% Evans Blue solution. Six hours later, tumors were excised and examined. The unstained area was attributed to necrotic tissue, whereas the stained area showed tissue with preserved blood supply. ZnPcCF(3) was accumulated in spleen, liver and duodenum. It suggests that ZnPcCF(3) is eliminated from the body via bile-gut. The phthalocyanine was not found in brain, therefore, it would not cross the blood-brain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF(3) does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2mg/kg ZnPcCF(3) resulted in a low acute toxicity with revertible damages, which indicates that this dose can be used for PDT. The tumor death was of 89% 4 days after PDT. It indicates that ZnPcCF(3) would be effective in PDT.
authors.affiliation: Universidad Nacional de Río Cuarto, Biologia Molecular, Ruta 8 Km 601, 5800 Río Cuarto, Córdoba, Argentina. lmilla@exa.unrc.edu.ar
authors.forename: Laura N
authors.initials: LN
authors.lastname: Milla
authors.forename: Edith I
authors.initials: EI
authors.lastname: Yslas
authors.forename: Ana
authors.initials: A
authors.lastname: Cabral
authors.forename: Edgardo N
authors.initials: EN
authors.lastname: Durantini
authors.forename: Silvia
authors.initials: S
authors.lastname: Romanini
authors.forename: Viviana
authors.initials: V
authors.lastname: Rivarola
authors.forename: Mabel
authors.initials: M
authors.lastname: Bertuzzi
mesh_terms: D000818:Animals; D005070:Evans Blue / Q000008:administration & dosage; D005260:Female; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D054833:Isoindoles; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution; D018675:Toxicity Tests; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D005070:Evans Blue