This paper describes investigations on the excretion of tritium in the urine, breath and faeces after therapeutic injections of tritiated tetra-sodium 2-methyl-I :I-naphthaquinol diphosphate in patients suffering from advanced malignant disease. Most of the tritiated material is excreted in the urin
Tritium uptake, half-lives and radiation doses in tissues of cancer patients treated with tritiated 2-methyl-1: 4-naphthaquinol diphosphate
โ Scribed by Barbara Chipperfield
- Publisher
- John Wiley and Sons
- Year
- 1967
- Tongue
- French
- Weight
- 842 KB
- Volume
- 2
- Category
- Article
- ISSN
- 0020-7136
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โฆ Synopsis
Comparisons of the uptake into tumour biopsies 30 min ajier intravenous or intraarterial injections showed that tumours of gastrointestinal origin took up signiJicantly greater amounts of the tritiated drugs than did any other group of tumours, and with other types of tumours some individual biopsies showed very high tumour specific activities afrer intra-arterial injections. The tritium in the turnour disappeared by two exponential decay processes, one with a half-life of 1.35 days and the other with a half-life of 14.4 days. The ratio of the concentration of the long-lived component to that of the short-lived component was 0.33.
Tritium estimations on normal tissues taken at autopsy from patients who received only one injection of the tritiated drug showed that the biological half-life in normal tissues ranged from 5.7 days (heart) to 34.5 days (long-lived component in brain). The initial specific activity in pclg for each clkg injected ranged from 71 (long-lived component in brain) to 505 (kidney).
After a single injection of 1 c of the drug per kg body weight, the greatest doses of radiation were received by the kidney (1,600 R ) , testis (1,300 R ) , liver (1,050 R ) and bruin (990 R). The lowest doses were received by skeletal muscle (39.5 R ) and bone marrow (604 R ) .
The radiation dose in the tumour depends on the initial concentration and the half-life in the tumour. Initial tumour concentrations of 5-8 mclg wet tissue should give radiation doses in the therapeutic range after a single injection.
A clinical investigation of the possible use of tritiated drugs in the treatment of cancer has been in progress in the Radiotherapeutic Centre, Addenbrooke's Hospital, Cambridge, and in this Department since 1959. The development of tritiated 2-methyl-I :4-naphthaquinol bis-disodium phosphate as a radioactive drug has been reviewed, along with the earlier use of the compound without tritium as a radiosensitizer (Marrian et al., 1961). The first compound to be used was 2-methyl-1 :4-naphthaquinol bisdisodium phosphate labelled with tritium by the Wilzbach technique (Wilzbach, 1957). Early investigations indicated that this compound might be taken up preferentially by tumour tissues with a half-life in the tumour of 13 days (Horwitz et al., 1959) but it was later found that when the tritium was incorporated into the
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