BIODISTRIBUTION OF I-125 LABELED DES(1-3)-INSULIN-LIKE-GROWTH-FACTOR-I IN TUMOR-BEARING NUDE-MICE AND ITS IN-VITRO CATABOLISM

Insulin-like growth factor I (IGF-I) is a potent mitogen for many tumo r cell lines, and IGF-I receptors are overexpressed in many tumors. Sp ecific IGF-binding proteins (IGFBPs) modulate the interaction of IGF a nd its receptors. Consequently, radiolabeled IGF-I has been considered for tumor imaging. In the present study, we investigated the biodistr ibution of I-125-labeled des(1-3)IGF-I, a truncated analogue of IGF-I, in tumor-bearing nude mice. Additional studies included its catabolis m by tumor cells in vitro and its binding to serum IGFBPs in vivo in n ude mice. We also compared groups that were and were not injected with unlabeled peptide analogue. Our data showed that I-125-labeled des(1- 3)IGF-I catabolized very fast, with a rapid appearance of nonprecipita ble iodine, when incubated at 37 degrees C, but it was not catabolized at 4 degrees C incubation. I-125-labeled des(1-3)IGF-I was bound to s erum-binding proteins, mainly in a complex with a molecular weight of M-r 150,000. The uptake of radioactivity in normal tissues decreased q uickly with time, particularly in the kidneys. In mice receiving highe r doses of des(1-3)IGF-I, the radioactivity in all normal tissues was lower than in the mice with no carrier-added des(1-3)IGF-I, except in the stomach and spleen. These data suggest that I-125-labeled des(1-3) IGF-I is rapidly internalized after binding to the IGF receptor and is rapidly catabolized with release of breakdown products. Lower specifi c activity of I-125-labeled des(1-3)IGF-I resulted in altered biodistr ibution, including faster blood clearance and higher tumor uptake, by decreasing the formation of complexes with IGFBPs.