Biodistribution of iodine-125 tyramine transforming growth factor α antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection

The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor α (TGFα) was the first growth factor to be associated with tumorigenesis, thus making the TGFα (mRNA) a potential target for AS therapy and offering the potential for monitoring of the progression of malignancy by non-invasive imaging with radiolabelled AS phosphodiester. Probe labelling and biodistribution were studied in the present report. A 23-mer oligonucleotide sequence was synthesized and grafted in 5′ with a tyramine group which was further radioiodinated. The radiolabelled AS was injected intratumorally in mammary tumour-bearing BALB/c mice (3 weeks after inoculation of 7·106 NS2T2A mammary cells). Biodistribution was monitored by sequential scintigraphy and organ radioactivity after autopsy. The 5′ tyramine group allowed specific and stable radiolabelling of the AS with125I. The125I AS oligonucleotide was rapidly cleared from the tumour by intestine and kidneys. Four hours after intratumoral injection, 6.5%±1.5% of the dose was retained in the tumour as non-degraded125I AS. It is concluded that 5′ tyraminylated AS provides information on the biodistribution of AS oligonucleotide following intratumoral injection. These data will contribute to the pharmacology of AS oligonucleotides which can be used for therapy.