| Background: Glioma is the most common malignant tumor in central nervous system with with invasive strong, easy to recurrence and so on. Clinical treatment with surgical resection combined with radiotherapy and / or chemotherapy, but the overall effect is still not satisfied. Radiation therapy for tumors is that radioactive substances is directly placed in the Tumor residual cavity, to avoid the blood-brain barrier and improve local drug concentration. Early experiments in vitro cytotoxicity and in vivo animal studies that show that, 125I-deoxyuridine (125I-5-iodo-2-deoxyuridine, 125IUdR) can inhibit tumor cell growth, animal survival was significantly longer than control group animals and did not show significant side effects. On this basis, the 125IUdR brain tumor radiation therapy research will be transferred to pre-clinical research stage. But first of all, you should study the pharmacokinetics and tissue distribution after transcranial injection of 125IUdR in animal ,to determine the next step of pre-clinical research schemes and provide the necessary data.Objective: In this study, it is determined pharmacokinetics and tissue distribution of indicators by intracranial injection 125IUdR (125I-5-iodo-2-deoxyuridine) in rats for 125IUdR tumor radiation treatment of cerebral glioma to provide the necessary pre-clinical study data with tissue radioactivity measurements and single photon emission computed tomography method (SPECT).Methods: The 42 health SD rats, weight (250±15) grams, divided into seven groups randomly, each group of 6 only. Two of the group for 125IUdR pharmacokinetics index measurement, the other five groups are used for determination of rats after intracranial injection 125IUdR tissue distribution experiment. In pharmacokinetic experiment , the rats in group A were subjected to intracranial injection 125I-UdR 0.1mCi and those in group B to intravenous injection of 125I-UdR 0.1mCi, serial blood samples were taken in the following administration 1min,10min,30 min,1h,2h,4h,8h,24h,48h,72h and measured byγscintillation counter. In tissue distribution experiment, 5 group of rats, each rat were confirmed by intracranial injection of 125IUdR 0.1mCi to the right caudate nucleus department, four of the group by 1h, 2h, 24h, 48 h after grouping executed, Acquisition 1ml blood and Anatomy of the following organs: the brain, thyroid, heart, lungs, liver, stomach and kidney, bladder, washing after using the filter paper to absorb water, put into a test tube weighted and measured byγscintillation counter. The other one group of rats, after injection in the brain 1h, 2h, 24h, 48h, SPECT scan lines at each time point, collecting images, acquisition time of 10min.Results: 125IUdR intracranial injection in rat time-blood concentration curve results of rat serum concentration is reduced after the first rise. Using the pharmacokinetic analysis software DAS ver1.0, the concentration-time curves after intracranial injection were fitted to a two-compartment model, an average of T1/2αwas 3.42h, T1/2βwas 36.58h, Cmax was 1.35μg/L, Tmax was 1.76h. After intravenous injection time - concentration curve shows injection 125IUdR 10min plasma concentrations decreased rapidly within, 10min after the easing, the whole process is down. The concentration-time curves after intravenous injection were fitted to a 1-compartment model, an average of T1/2 was 0. 10 h , Cmax was 36.40μg/L,Tmax was 0.00 h . Rats were dissected after intracranial injection of various organs, in the 2h time point 125IUdR per gram of tissue uptake was higher than the other three time points, with the average peak time of drug consistent Tmax. After intracranial injection with SPECT scanning, directly into the image to display in the distribution of various organs, each time point 125IUdR in the brain, liver, stomach, lung, kidney, bladder, and other organs. Region of interest in the brain is the decrease in radioactivity, but other areas of radioactivity in organs of interest is first increased and then decreased . The SPECT 125IUdR of metabolism and distribution of organs is similar to radioactive measurements of anatomy. Conclusion: The metabolism in rats with Intracranial injection 125IUdR were fitted to a two-compartment model. 125IUdR is absorbed non-specific mainly by the kidney metabolism, gastric mucosa. The 125IUdR distribution of SPECT imaging in the body is similar to conventional radioactive measurement results, this method can be dynamic observation and is more simple and intuitive. |
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