Pharmacokinetics of gene recombined angiogenesis inhibitor Kringle 5 in vivo using (131)I specific markers and SPECT/CT()

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific (131)I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of (131)I-Kringle 5 in vivo, and to investigate the dynamic distributions of (131)I-Kringle 5 in target organs. Labeling recombinant angiogenesis inhibitor Kringle 5 using (131)I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of (131)I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t(1/2α), t(1/2β), apparent volume of distribution and CL between those three levels. The ratio of AUC((0~∞)) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after (131)I-Kringle 5 was injected, (131)I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that (131)I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of (131)I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker (131)I-Kringle 5 and SPECT/CT were successfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of (131)I-Kringle 5.