Photodynamic activities and biodistribution of fluorinated zinc phthalocyanine derivatives in the murine EMT‐6 tumour model

• Published in: International journal of cancer 1997-07, Vol.72 (2), p.289-294
• Main Authors: Allémann, Eric, Brasseur, Nicole, Kudrevich, Svetlana V., La Madeleine, Carole, van Lier, Johan E.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Female; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacokinetics; Fluorescent Dyes - therapeutic use; Indoles - chemistry; Indoles - pharmacokinetics; Indoles - therapeutic use; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - therapy; Medical sciences; Mice; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - therapeutic use; Photoradiation therapy and photosensitizing agent; Phototherapy; Radiation-Sensitizing Agents - chemistry; Radiation-Sensitizing Agents - pharmacokinetics; Radiation-Sensitizing Agents - therapeutic use; Treatment with physical agents; Treatment. General aspects; Tumors; Zinc
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970717)72:2<289::AID-IJC15>3.0.CO;2-B

The photodynamic properties and biodistribution pattern of zinc dodecafluoro‐4‐sulphophthalocyanine (ZnPcF12S1), zinc hexadecafluorophthalocyanine (ZnPcF16) and zinc phthalocyanine (ZnPc) were evaluated in the murine EMT‐6 tumour model. All 3 dyes were formulated as a Cremophor oil–water emulsion after initial solubilization in methanol, acetone and pyridine, respectively. Comparison of their phototoxicity after in vitro incubation with EMT‐6 cells and exposure to various fluences of red light showed that ZnPcF12S1 is about 50 times more active than ZnPcF16, reflecting better cell‐penetrating properties. Solubilisation of ZnPc in 1‐methyl‐2‐pyrrolidinone prior to formulation resulted in loss of photo‐activity upon dilution in serum due to precipitation of the dye in the aqueous environment. In contrast, initial solubilisation in pyridine likely forms a ZnPc‐pyridinium salt, and this preparation was 6 times more phototoxic than ZnPcF12S1. In vivo comparison of monosulphonated ZnPcF12S1 with perfluorinated ZnPcF16 showed improved pharmacokinetics in mice, including lower liver and spleen retentions and higher tumour‐to‐non‐target tissue ratios. However, photodynamic therapy (PDT) of the EMT‐6 tumour in BALB/c mice with red light, 24 or 48 hr post‐injection of 1 μmol · kg−1 of ZnPcF12S1 induced mortality. Lowering the drug and/or light dose or extending the time interval between drug administration and irradiation to 72 hr avoided adverse effects but also resulted in poor tumour response. The best tumour control (25% of animals) was obtained at 0.1 μmol · kg−1 and a fluence of 400 J · cm−2 at 24 hr post‐injection. In contrast, ZnPcF16 required a 20‐fold higher drug dose to induce a similar tumour response. The systemic shock following PDT with the amphiphilic ZnPcF12S1 likely results from extensive cellular effects. Int. J. Cancer 72:289–294, 1997. © 1997 Wiley‐Liss, Inc.