Radioimmunoassay of the anti-cancer agent 4-hydroxyandrostenedione in body fluids.
Antibodies were produced in sheep against a new anti-breast cancer drug 4-hydroxyandrostenedione (4-OHA) using two hapten-ovalbumin conjugates. One of these conjugates (4-hydroxytestosterone-ovalbumin) produced an antiserum suitable for the development of a radioimmunoassay that would allow direct measurement of 4-OHA in plasma at concentrations down to 82 pmol/l, with adequate accuracy, precision and scope for further sensitivity. Although this assay would measure 4-hydroxytestosterone (4-OHT) in addition to 4-OHA, the present data suggest that the magnitude of any interference from endogenous steroids and those derived from 4-OHA could only be minimal. A comparison of solvent-extracted and unextracted samples showed that only unconjugated drug was analysed by this radioimmunoassay. A study of plasma protein binding of 4-OHA showed that at therapeutic concentrations, between 13.5 and 16.5% of plasma 4-OHA was not bound to proteins. This assay system could be a useful adjunct to the future development of 4-OHA as an anti-cancer drug.
Khubieh
J
J
Department of Biochemistry, University of Surrey, Guildford, England.
Aherne
G W
GW
Chakraborty
J
J
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000032:analysis* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001826:Body Fluids / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011485:Protein Binding; D011863:Radioimmunoassay
D000970:Antineoplastic Agents; D001798:Blood Proteins; D000735:Androstenedione; C014594:formestane