Improved estimates of clearance of 131I-labelled insulin-like growth factor-I carrier protein complexes from blood plasma of sheep.

Clearance of protein-bound forms of insulin-like growth factor-I (IGF-I) from the circulation of sheep was determined using single injections of 131I-labelled ovine or [Thr59]-human IGF-I, in the 'free' form or prebound to 50 or 150 kDa plasma binding protein fractions. The half-life of circulating protein-bound forms of IGF-I was determined by size-exclusion chromatography of plasma samples taken over a 24- to 26-h experimental period. IGF-I bound to lower molecular weight binding protein(s) (approximately 50 kDa) showed a half-life of 26-40 min (mean 34 min; n = 6), while the half-life of a high molecular weight fraction (150 kDa) was considerably longer (range 398-603 min; mean 545 min; n = 8). Metabolic clearance of IGF-I following administration of free tracer ranged from 3.0 to 5.3 ml/min in sheep (n = 4) weighing 26.0-28.5 kg. Tracer distribution volume was 59 ml/kg liveweight (n = 4). Tracer degradation products were first detected in plasma 8 h after i.v. administration. No differences in stability of the purified ovine and recombinant human IGF-I tracer preparations were observed. However, a fraction of the [Thr59]-IGF-I tracer did not possess binding activity and this was associated with excretion of a greater proportion of administered radioactivity (over 22 h) in urine in animals receiving [Thr59]-IGF-I tracer (18.4-19.3%) compared with ovine IGF-I (7.1-11.0%).(ABSTRACT TRUNCATED AT 250 WORDS)