Synthesis and radioiodination of a meso‐tetra (hydroxynaphthyl) porphyrin and its sulphonated derivative as potential tumour localizers

Abstract

SUMMARYThe synthesis and radiolabelling with iodine-125 of a sulphonated and non-sulphonated meso-tetra(hydroxynaphthy1) porphyrin is described.Complete demethylation of the meso-tetra (methoxynaphthyl) porphyrin precursor to form the corresponding hydroxynaphthyl derivative could not be achieved using HBr. Sulphonation and radioiodination reactions were thus carried out on a mixture of hydroxy/methoxynaphthyl porphyrins. The weak mass spectrum exhibited by the sulphonated porphyrin derivative may reflect the highly polar nature of the compound. Neither of the iodinated porphyrins were found to localise in tumour tissue to any appreciable extent. Spleen uptake of the iodinated hydroxynaphthyl porphyrin was found to be much greater in tumour bearing mice than in normal (non-tumour bearing) mice. This may be a result of porphyrin aggregation due to its limited water solubility.

Radiolabelled porphyrins in nuclear medicine

“…Inclusion of highly aromatic groups such as naphthyl groups in the place of the porphyrin phenyl groups have been shown to increase tumour uptake; however, whilst attempts to radiolabel sulfonated and unsulfonated 5,10,15,20‐tetrakis(2‐hydroxynaphthyl)porphyrin with 125 I have been made, neither of the compounds were shown to have significant tumour uptake, with activity strongly associated with the liver and spleen . To increase the hydrophilicity of the porphyrin, Lee et al .…”

“…Inclusion of highly aromatic groups such as naphthyl groups in the place of the porphyrin phenyl groups have been shown to increase tumour uptake; however, whilst attempts to radiolabel sulfonated and unsulfonated 5,10,15,20-tetrakis(2hydroxynaphthyl)porphyrin with 125 I have been made, neither of the compounds were shown to have significant tumour uptake, with activity strongly associated with the liver and spleen. 78 To increase the hydrophilicity of the porphyrin, Lee et al introduced methylene carboxylic acid groups to give 5-(3-(3-[ 123 I]iodoallyloxy)phenyl)-10,15,20-tris-(3-carboxymethoxyphenyl)porphyrin, with labelling achieved using the stannane precursor. Biodistribution studies showed a timedependent accumulation of porphyrin in tumour tissue with 10.35% ID/g at 6 h. The tracer was shown to have significant activity in the blood, liver, kidneys and spleen, but all organs except the liver were shown to have fast washout after 6 h p.i.…”

Regiospecific naphthyl nitration of 5,10,15,20‐tetranaphthylporphyrin

“…Tetranaphthylporphyrin (TNP) (Fig. 1) possesses larger aromatic rings compared with tetraphenylporphyrin (TPP),7 and its derivatives were reported to exhibit stronger tumor localization properties. In 1981, Zanelli and Kaelin8 found that a sulfonated derivative of meso ‐tetranaphthylporphyrin (TNPs) has quite good tumor‐localizing properties.…”