Meso-Tetra(hydroxyphenyl)porphyrins, a new class of potent tumour photosensitisers with favourable selectivity

Abstract

Summary We compared para-, meta-and ortho-isomers of meso-tetra(hydroxyphenyl)porphyrin (p-, m-and o-THPP) and the potassium salt of the para compound (K-p-THPP) with haematoporphyrin derivative (HpD) and Photofrin II in their ability to sensitise tumours, skin and brain to light. HpD and Photofrin II induced modest tumour photosensitisation at the cost of substantial skin and brain sensitisation. At doses low enough to keep sensitisation of these normal tissues within acceptable limits, tumour sensitisation was sufficient to give necrosis only 2mm deep after exposure to 1OJcm-2 light.In contrast, doses of p-THPP, K-p-THPP and m-THPP that produced skin and brain sensitivity within acceptable limits sensitised tumours enough to give 4-9mm necrosis after OJCcm-2 light. m-THPP was, on a molar basis, about 25-30 times as potent as HpD and Photofrin II in sensitising tumours. o-THPP was also a potent tumour photosensitiser, but induced a prohibitive degree of skin photosensitivity even at low doses.It is unlikely that these differences in relative selectivity are due to differences in such photophysical parameters as optimum activating wavelength (which would affect tissue penetration by light), or light absorption, and physicochemical factors that determine tissue localisation may be involved.The high tumour sensitising potency and favourable tissue selectivity of m-THPP, p-THPP and K-p-THPP make them promising candidates for clinical tumour phototherapy.

Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

“…Recently, mTHPC has shown to be a very effective photosensitizer in various tumour models and clinical trials (Ris et al, 1991;Lofgren et al, 1994;Peng et al, 1995;Dilkes et al, 1996;Grosjean et al, 1996;Mlkvy et al, 1997), with possible preferential uptake in a colon carcinoma in mice compared to liver concentrations (Whelpton et al, 1995). Furthermore, mTHPC drug and light doses needed to induce tumour necrosis are much lower than that of HpD (Berenbaum et al, 1986).…”

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…mTHPP itself was identified by Bonnet et al to be a promising PS. A significant screen was carried out showing mTHPP to be 25-30 times better than HpD in tumor models as a PS [238,239] . Several in vitro and in vivo studies have been carried out displaying the advantages of mTHPP [239][240][241][242] .…”

The role of photodynamic therapy (PDT) physics

“…Tetra ͑m-hydroxyphenyl͒ chlorin ͑mTHPC, Foscan®͒ is another second generation photosensitizer, a pure synthetic chlorin compound, which is activated by 652 nm light. 60 The major advantages of mTHPC are a short duration of skin photosensitivity ͑15 days͒, a high quantum yield for singlet oxygen, and depth of tumor necrosis of up to 10 mm in preclinical models. 61 mTHPC has been used for treatment of pleural mesothelioma, 7 head-and-neck cancers, 62,63 esophagus, 64,65 prostate, 10,66 pancreas, 67 arthritic joints, 68 and skin cancers 69 and was approved in Europe for PDT of head-and-neck and varieties of other tumors in 2001.…”