Effects of insulinlike growth factor binding proteins on insulinlike growth factor-I biodistribution in @entity5 -bearing XXXX .

@entity35 @entity5 @entity1792 @entity19 @entity30056 @entity7424
This study evaluated the biodistribution and @entity5 targeting ability of radiolabeled @entity7424 . Because IGF binding proteins (IGFBPs) play a critical role in modulating IGF activity, the binding properties of 125I-labeled @entity7424 to IGFBPs were investigated in vitro and in vivo. Because a large amount of the @entity7424 was catabolized in vivo, we also studied the catabolism of @entity7424 by @entity5 cells in vitro. METHODS: 125I-labeled- @entity7424 was prepared using the @entity30056 method. The biodistribution of 125I-labeled- @entity7424 in @entity5 -bearing @entity19 was compared between groups injected with 125I-labeled @entity7424 alone or coinjected with unlabeled peptide. In vitro and in vivo chromatography studies were performed to evaluate the binding profile to IGFBPs and the degree of catabolites in serum as well as urine. RESULTS: Data indicated that the binding of radiolabeled @entity7424 to IGFBPs in vitro was dose dependent. However, there was a difference in complex formation between the serum and the heparinized plasma. In heparinized plasma, the radioactivity shifted from a 30- to 50-kDa complex to a 150-kDa complex and to a free ligand, because the binding of heparin with IGFBPs decreased its affinity for @entity7424 . In plasma prepared with acid @entity1792 dextrose a binding pattern identical to that of serum was observed. Moreover, there was a binding difference between @entity19 and @entity35 . The 125I-labeled @entity7424 catabolized very quickly when incubated at 37 degrees C but not at all at 4 degrees C. In @entity5 -bearing @entity19 , the uptake of radioactivity in normal tissues decreased quickly, particularly in the kidneys. In @entity19 coinjected with unlabeled carrier, the radioactivity in most normal tissues was lower and the @entity5 uptake higher than in the @entity19 without carrier. CONCLUSION: These data confirm that 125I-labeled @entity7424 is avidly bound to IGFBPs, both in vitro and in vivo. By partially saturating this binding with unlabeled peptides, a favorable biodistribution was achieved, including faster clearance from normal tissue and higher @entity5 uptake, which resulted in better @entity5 -to-nontumor ratios. Nevertheless, the rapid catabolism and release of the radiolabel from @entity5 tissue result in a suboptimal targeting agent.
