Photofrin

Nowak-Sliwinska P, Karocki A, Elas M, Pawlak A, Stochel G, Urbanska K (2006) Vertepor-fin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells. Biochem Biophys Res Commun 349 549-555... 

It will not be lost on the reader that, while PHOTOFRIN and compounds (3), (5) and (6) contain no metal, they would be expected to be excellent ligands. Are metal complexes useful as PDT photosensitizers Indeed, they are, and may be expected in the future to become more important. The rest of this chapter is about this aspect it will emphasize metal complex formation and properties in relation to PDT. The synthesis of ligands, while of crucial importance, will not usually be treated here in detail, but leading references to relevant synthetic organic chemistry will be provided. The synthesis of porphyrins and related compounds has been considered in several monographs and reviews (porphyrins,46 47 phthalocyanines48). 

Misawa, J., Moriwaki, S.I., Kohno, E., Hirano, T., Tokura, Y., Takigawa, M. (2005) The role of low-density lipoprotein receptors in sensitivity to killing by Photofrin-mediated photodynamic therapy in cultured human tumor cell lines. J. Dermatol. Sci. July 20. 

Several research groups probably inspired by both the attractive features of PDT and the commercialization of Photofrin and Visudyne , have put considerable effort on the development and study of the so-called second generation photosensitisers. 

The new derivatives 121a (A-C) and 122a (A-C) were evaluated for their photocytotoxic activities in comparison with Photofrin , the commercial anti-cancer hematoporphyrin derivative formulation. Compounds 121a (A-C) have revealed to be more PDT efficient than Photofrin , but surprisingly compounds 122a (A-C) have shown to be inactive. 

All these derivatives showed significant photocytotoxic activity, with a phototoxic effect lower than the one observed with the commercial formulation Photofrin , when the dead cells were counted immediately after irradiation. 

Hematoporphyrin derivative or Photofrin was the first PS to be studied in detail. However, it proved highly frustrating for scientists who attempted to determine its chemical structure and to identify its components (Kessel, 1986, 1989b Kessel and Thompson, 1987 Kessel et al., 1987a, b). There was significant variation between batches and attempts to fractionate it into its individual component molecules frequently yielded mixtures as complicated as the starling material (Kessel, 1982, 1989a). 

Fig. 4.9 Comparison of PDT-induced killing in human ovarian cancer cells by BF4 or Photofrin both incubated for 24 h at 2(uM concentration and illuminated with red (630 nm) or white light...

Flahn SM, Putt ME, Metz J, Shin DB, Rickter E, Menon C, Smith D, Glatstein E, Fraker DL, Busch TM (2006) Photofrin uptake in the tumor and normal tissues of patients receiving intra-peritoneal photodynamic therapy. Clin Cancer Res 12 5464-5470. 

Li Lb, Luo Re, Liao Wj, Zhang Mj, Luo Yl, Miao Jx (2006) Clinical study of Photofrin photodynamic therapy for the treatment of relapse nasopharyngeal carcinoma. Photodiagnosis and Photodynamic Therapy 3 266-271. 

Buettner, G. R., KeUey, E. E., and Bums, C. P., 1993, Membrane hpid free radicals produced from LI 210 murine leukemia ceUs by photofrin photosensitization an electron paramagnetic resonance spin trapping study. Cancer Res. S3 3670-3673. 

Work during the last ten years on photodynamic therapy (PDT) has established the methodology as effective in the early treatment of cancers, and in the treattnent of certain skin disorders and viral infections. Approval by the regulatory authorities for sensitisers in this process began in 1993 when Canada allowed the use of Photofrin (QLT Therapeutics), an action followed later by most countries around the world. Now many other companies have sensitisers at late stage clinical dials (2001), see below in Table 4.5. An excellent introduction to the chemistry of this topic is provided in the book written by Bonnett. ... 

Although there are many dyes which can photosensitise the production of singlet oxygen (see section 4.4.1), in PDT the first products of real interest came from haematoporphyrin. Subsequent, studies led to the haematoporphyrin derivatives HpD Stage 1 and Stage 11, which were found to be more active as PTD sensitisers as they localised preferentially in tumours. The first commercially available sensitiser, Photofrin, is based on processed material from HpD Stage 11, and is a complex mixture of monomeric, dimeric and oligomeric e.g. hexamer) porphyrins, in an... 

Table 4.5 Comparison of 2nd generation sensitisers with photofrin... 

Photofrin (QLT) 628 (3000) 0.89 1.2-5 75-250 750-2500 Early treatment of bladder, lung, esophagus, cervix, stomach and mouth Palliative in later stages Skin phototoxicity (up to 4 weeks) is a problem (Approved, esophegal and lung)... 

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