Abstract
The tritium-labelled analogues of pimonidazole and RSU 1069 were injected into mice bearing the KHT murine sarcoma which has a hypoxic cell fraction of approximately 10%. The distribution of activity at 24 h was recorded using autoradiography and measurement of tissue activity. Autoradiographs with both drugs showed high activity in particular cells within tumour, eye (melanin-associated cells), eyelid (Meibomian gland), liver (centrilobular area), skin (sebaceous gland and melanin), stomach (squamous area), footpad, oesophagus, labial gland, Zymbal's gland, preputial gland, parotid gland (intralobular ducts) and airway epithelium. These tissues had previously been identified as sites of binding of misonidazole. The measurement of total tissue radioactivity showed significantly higher activity in liver, eyelid (Meibomian gland), oesophageal lining, kidney and labial gland than was found in the tumour.
Highlights
Phenomenon is specific to MISO or can be observed more widely
Pimonidazole (a-[(2-nitro-1-imidazolyl)methyl]-1-piperidine-ethanol; RO 03-8799; PIMO) is a lipophilic MISO analogue in which the methoxy group has been replaced by a piperidine group (Smithen et al, 1980)
The theory that the basic side-chain could lead to improved concentration in the acidic milieu of tumours is supported by the work of Dische et al (1986a,b) and Roberts et al (1986) who have observed in patients a tumour concentration of approximately twice that of MISO
Summary
Pimonidazole (a-[(2-nitro-1-imidazolyl)methyl]-1-piperidine-ethanol; RO 03-8799; PIMO) is a lipophilic MISO analogue in which the methoxy group has been replaced by a piperidine group (Smithen et al, 1980). The theory that the basic side-chain could lead to improved concentration in the acidic milieu of tumours is supported by the work of Dische et al (1986a,b) and Roberts et al (1986) who have observed in patients a tumour concentration of approximately twice that of MISO. This compound has had a limited clinical trial (Saunders et al, 1984; Roberts et al, 1986). In a limited clinical trial it has been found to cause the side-effects of nausea and vomiting (Horwich et al, 1986)
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