ABSTRACT
[Objective]To radiolabel the PSMA aptamer A10-3.2 with 99mTc , and explore its biological characteristics in vivo and in vitro.[Methods]Using Succinimidyl 6-hydrazinonicotinate hydrochloride (SHNH) as the bifunctional chelating agent to label aptamer A10-3.2 with 99mTc, then tested for the stability in vitro, the specific uptake by prostate cancer LNCaP cells (PSMA+) , the characteristics of SPECT/CT imaging and biodistribution in LNCaP tumor-bearing NOD/SCID mice.[Results]The labeling rate and radiochemical purity of the products (99mTc-SHNH-A10-3.2) are(71.31 ± 6.78)% and 97.03%,respectively. 99mTc-SHNH-A10-3.2 had obvious target specificity for PSMA positive prostate cancer LNCaP cells, its uptake rate was significantly higher than PSMA nega?tive PC-3 cells (P<0.01). And in tumor-bearing mice, the tumor has a certain uptake and a high ratio of the tumor tissue to the mus?cle.[Conclusion]This study successfully constructed 99mTc-labeled PSMA-targeted aptamer A10-3.2, which has a good stability and targeting in vivo and in vitro, has a high tumor tissue/muscle ratio in tumor-bearing mice, which show that it may be a potential target?ed molecular imaging agent for prostate cancer.
ABSTRACT
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 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-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 t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) 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 131I-Kringle 5 was injected, 131I-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 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-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 131I-Kringle 5 and SPECT/CT were suc-cessfully 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 131I-Kringle 5.