PMID- 9014847
OWN - NLM
STAT- MEDLINE
DCOM- 19970220
LR  - 20190709
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 152
IP  - 1
DP  - 1997 Jan
TI  - Actions of an IGF-I-enhancing antibody on IGF-I pharmacokinetics and tissue 
      distribution: increased IGF-I bioavailability.
PG  - 123-30
AB  - We have previously demonstrated that a specific anti-IGF-I antibody will enhance 
      the growth-promoting activity of IGF-I in vivo (Stewart et al. 1993). Since the 
      antibody had a modest affinity for IGF-I we suggested that the antiserum might 
      protect IGF-I from degradation whilst maintaining it in a bioavailable form. The 
      aim of this investigation was to test that hypothesis by determining the plasma 
      clearance and tissue distribution of tracer IGF-I in the presence of the 
      enhancing anti-IGF-I immunoglobulin (anti-IGF-I Ig) or non-immune immunoglobulin 
      (NI Ig). Dwarf rats were treated with saline, NI Ig or anti-IGF-I Ig for 4 days. 
      On day 4, 125I-IGF-I (1.6 x 10(7) c.p.m.) was injected into the jugular vein and 
      blood sampled over the next 330 min when the rats were killed: samples of liver, 
      kidney and skeletal muscle were quickly dissected out. Mean plasma 
      trichloroacetic acid (TCA)-precipitable 125I-IGF-I was always significantly 
      greater (P < 0.001 for each time point) from anti-IGF-I Ig rats versus the NI Ig 
      or saline groups (which exhibited practically identical decay curves), implying 
      increased binding capacity for IGF-I in the anti-IGF-I Ig rats. Pharmacokinetic 
      parameters were calculated by resolution of the decay curves using a two-phase 
      model. The total clearance rate of 125I-IGF-I was significantly decreased (P < 
      0.001) by almost twofold in the anti-IGF-I versus the two control groups, 
      consistent with the increased binding capacity in the anti-IGF Ig rats. The 
      half-lives of the faster-decaying phase were not significantly different between 
      treatment groups but, surprisingly, that for the slower-decaying phase was 
      significantly decreased (P < 0.001) in the anti-IGF-I Ig rats versus the two 
      control groups; this may reflect the low affinity of the anti-IGF-I Ig for IGF-I 
      and its enhancing properties. The degradation of 125I-IGF-I was significantly 
      decreased in animals receiving the anti-IGF-I Ig. In support of this, kidney 
      TCA-precipitable radioactivity (c.p.m.) was seven-fold less (P < 0.001) in the 
      anti-IGF-I Ig groups versus the controls, indicative of reduced excretion. Liver 
      TCA-precipitable radioactivity was increased (P < 0.001) in the anti-IGF-I Ig 
      rats, probably due to reticuloendothelial clearance of non-self antibodies: 
      skeletal muscle TCA-precipitable radioactivity tended to increase in the 
      anti-IGF-I Ig group versus the controls which might indicate increased targeting 
      of IGF-I to muscle. Size exclusion chromatography of plasma 15 and 120 min after 
      administration of 125I-IGF-I demonstrated a broad peak of radioactivity with a 
      molecular mass of 150-300 kDa in the anti-IGF-I Ig-treated rats, which was 
      responsible for more than 90% of the eluted radioactivity. This suggests that: 
      (1) 125I-IGF-I was bound to the anti-IGF-I Ig and might also be able to associate 
      with IGFBPs or (2) the polyclonal antibody might recognise more than one 
      antigenic site on IGF-I. These data indicate that the anti-IGF-I Ig was 
      protecting IGF-I from degradation, leading to a large plasma pool of IGF-I but 
      that IGF-I could be transferred readily from the plasma pool to tissues. We 
      suggest that administration of IGF-I in conjunction with a binding molecule 
      similar to the antibody described here could provide the basis for effective 
      IGF-I treatment strategy.
FAU - Hill, R A
AU  - Hill RA
AD  - Department of Cellular Physiology, Babraham Institute, Cambridge, UK.
FAU - Flick-Smith, H C
AU  - Flick-Smith HC
FAU - Dye, S
AU  - Dye S
FAU - Pell, J M
AU  - Pell JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Immune Sera)
RN  - 0 (Immunoglobulins)
RN  - 0 (Iodine Radioisotopes)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Biological Availability
MH  - Chromatography
MH  - Female
MH  - Immune Sera/*pharmacology
MH  - Immunoglobulins/pharmacology
MH  - Insulin-Like Growth Factor I/*immunology/*pharmacokinetics
MH  - Iodine Radioisotopes/pharmacokinetics
MH  - Metabolic Clearance Rate
MH  - Rats
MH  - Rats, Mutant Strains
MH  - Tissue Distribution
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1677/joe.0.1520123 [doi]
PST - ppublish
SO  - J Endocrinol. 1997 Jan;152(1):123-30. doi: 10.1677/joe.0.1520123.