title: Biodistribution of iodine-125 tyramine transforming growth factor alpha antisense oligonucleotide in athymic mice with a human mammary tumour xenograft following intratumoral injection.
abstract: The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor alpha (TGFalpha) was the first growth factor to be associated with tumorigenesis, thus making the TGFalpha (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 7.10(6)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 with 125I. The 125I 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-degraded 125I 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.
authors.affiliation: Laboratory of Radiopathology, Institut Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Cammilleri
authors.forename: S
authors.initials: S
authors.lastname: Sangrajrang
authors.forename: B
authors.initials: B
authors.lastname: Perdereau
authors.forename: F
authors.initials: F
authors.lastname: Brixy
authors.forename: F
authors.initials: F
authors.lastname: Calvo
authors.forename: H
authors.initials: H
authors.lastname: Bazin
authors.forename: H
authors.initials: H
authors.lastname: Magdelenat
mesh_terms: D000005:Abdomen / Q000000981:diagnostic imaging; D000818:Animals; D004355:Drug Stability; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense; D011877:Radionuclide Imaging; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D013997:Time Factors; D014018:Tissue Distribution; D016211:Transforming Growth Factor alpha / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D007457:Iodine Radioisotopes; D016376:Oligonucleotides, Antisense; D016211:Transforming Growth Factor alpha