Synthetic porphyrins as tumour-localizing agents

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.