Premium
Photodynamic activities and biodistribution of fluorinated zinc phthalocyanine derivatives in the murine EMT‐6 tumour model
Author(s) -
Allémann Eric,
Brasseur Nicole,
Kudrevich Svetlana V.,
La Madeleine Carole,
van Lier Johan E.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970717)72:2<289::aid-ijc15>3.0.co;2-b
Subject(s) - biodistribution , photodynamic therapy , zinc , cancer research , chemistry , phthalocyanine , medicine , pathology , biochemistry , organic chemistry , in vitro
The photodynamic properties and biodistribution pattern of zinc dodecafluoro‐4‐sulphophthalocyanine (ZnPcF 12 S 1 ), zinc hexadecafluorophthalocyanine (ZnPcF 16 ) 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 ZnPcF 12 S 1 is about 50 times more active than ZnPcF 16 , 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 ZnPcF 12 S 1 . In vivo comparison of monosulphonated ZnPcF 12 S 1 with perfluorinated ZnPcF 16 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 ZnPcF 12 S 1 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, ZnPcF 16 required a 20‐fold higher drug dose to induce a similar tumour response. The systemic shock following PDT with the amphiphilic ZnPcF 12 S 1 likely results from extensive cellular effects. Int. J. Cancer 72:289–294, 1997. © 1997 Wiley‐Liss, Inc.