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

被引:33
作者
Cammilleri, S
Sangrajang, S
Predereau, B
Brixy, F
Calvo, F
Bazin, H
Magdelenat, H
机构
[1] INST CURIE,LAB RADIOPATHOL,F-75231 PARIS 05,FRANCE
[2] ST LOUIS HOSP,PHARMACOL LAB,PARIS,FRANCE
[3] CIS BIO INT PROBE MOL LAB,BAGNOLS SUR CEZE,FRANCE
来源
EUROPEAN JOURNAL OF NUCLEAR MEDICINE | 1996年 / 23卷 / 04期
关键词
transforming growth factor alpha; antisense phosphodiester oligonucleotide; radioiodine labelling; biodistribution;
D O I
10.1007/BF01247375
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
The Watson-Crick base pairing rule provides the underlying principle for the antisense (AS) approach to inhibiting gene expression. Transforming growth factor alpha (TGF alpha) was the first growth factor to be associated with tumorigenesis, thus making the TGF alpha (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 I-125. The I-125 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 I-125 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.
引用
收藏
页码:448 / 452
页数:5
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