Synthetic porphyrins as tumour-localizing agents

Abstract

A series of radioactively labelled porphyrin analogues have been synthesized and compared for tissue distribution and tumour uptake against 67Ga in the same tumour-mouse system. The compounds were: 14C-ms-tetraphenylporphine sulphonate (14C-TPPS), 35S-ms-tetraphenylporphine sulphonate (TPP35S), 35S-ms-tetra[beta-naphthyl]porphine sulphonate (TNP35S), 14C-ms-thienylphenylporphine sulphonate (14C-TTPPS) and 35S-ms-tetra[p-tolyl]porphine sulphonate (TTP35S). 14C-TPPS and TNP35S appear to concentrate in tumours to a greater extent than 67Ga (ratios of tumour uptake for TPPS/67Ga and TNPS/67Ga were about two and three respectively) but their uptake in kidneys and lungs was also greater than that of gallium. The type of side group attached to the central tetrapyrrole ring appears to have a substantial effect on the tumour-localizing properties of these compounds. Comparison of 14C and 35S-labeled TPPS indicates that the sulphonate groups are split off in vivo and that compounds with highly aromatic side groups (e.g. TNPS) and a radioactive label in a non-labile part of the molecule (e.g. in the tetrapyrrole ring system itself) would show even better tumour localization. The feasibility of synthesizing porphyrins with a variety of reactive side groups suggests that it may be possible to introduce suitable gamma-emitters while retaining the tumour-localizing properties.

Iodinated hydroxyphenyl and hydroxynaphthyl porphyrins as tumour localisers

“…These authors, however, quantitated the effectiveness of their compounds by their relative ability to induce necrosis in transplanted animal tumours after irradiation with light of the appropriate wavelength. (Zanelli & Kaelin, 1981), a tetra-hydroxynaphthyl porphyrin was also synthesised, iodinated and its distribution in the same mouse-tumour model determined.…”

Tumour scanning with indium-111 dihaematoporphyrin ether

“…radiolabelled porphyrins and metalloporphyrins for tumour detection in vivo (Figge et al, 1948;Manganiello & Figge, 1951;Bases et al, 1958;Winkelman et al, 1962), but with varying degrees of success. A major problem with the use of these agents has been their high degree of accumulation in the liver, spleen and kidneys (Hambright et al, 1975;Denechaud et al, 1981;Zanelli & Kaelin, 1981). Attempts to image tumours with "'In labelled porphyrins have been limited (Vaum et al, 1982;Foster et al, 1985).…”

“…Metallation of hematoporphyrin in the tetrapyrrole ring is considered to have an inhibitory effect on tumour affinity for the agent (Zanelli & Kaelin, 1981;Wang et al, 1981 (Bugelski et al, 1981), but another uptake mechanism by tumour may also be involved. Kessel (1986) has described the binding of tumour-localising porphyrins to high and low density lipoproteins (HDL and LDL) which have been shown to transport HPD (Jori et al, 1984;Reyftmann et al, 1984).…”

The Use Of Porphyrins And Non-Ionizing Radiation For Treatment Of Cancer

“…the answer is no. Still, a number of investigations reveal a favourable tumour to other tissue ratio for several porphyrin species (27)(28)(29)(30)(31)(32). However, except for the one proposed by us (30).…”