Diffusion of insulin-like growth factor 1 in human breast cancer explants.
Tumor explants, from 15 patients with primary breast cancers, were incubated in organ culture medium containing [125I]IGF1. Measurements of explant radioactivity were performed in order to evaluate IGF1 uptake and release as a function of time, medium concentration and patient, in tumors with low IGF1 receptor levels. Uptake and release were governed by a passive diffusion mechanism and could be well described by a pharmacokinetic-like model. The rate of uptake depended on patient but affinity of IGF1 for the tumor tissue was always higher than affinity for the medium. Moreover the rate of uptake was faster than IGF1 clearance in man. From these results it can be extrapolated that the IGF1 circulating level must strongly influence the tumor content, independently of the receptor level. In the same way, IGF1 analogs could be administered via blood injection and the administration could be monitored by the above described pharmacokinetic model.
Hecquet
B
B
Laboratoire de Pharmacodynamie Clinique, Centre Oscar Lambret, Lille, France.
Peyrat
J P
JP
D001943:Breast Neoplasms / Q000378:metabolism*; D003470:Culture Media; D046508:Culture Techniques; D004058:Diffusion; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics*; D008433:Mathematics; D008954:Models, Biological; D012588:Scintillation Counting
D003470:Culture Media; D007334:Insulin-Like Growth Factor I