The Experimental Study On Biosynthesis And Anti-tumor Affect Of ¹³¹I-Tyr-Octreotide On NSCLC

Objective Radionuclide labeling low molecular weight polypeptide is hotspot for the diagnosis and treatment of malignant tumor. The purpose of this study is to evaluate the reaction condition of biosynthesis by chloramine-T,radiochemical purity and stability of ¹³¹I-Tyr-Octreotide,observe its biodistribution and metabolism in mice, observe the tumor uptake of ¹³¹I-Tyr-Octreotide,and evaluate the anti-tumor effect of it on nude mice bearing human non-small cell lung cancer (NSCLC).Methods Biosynthesis of Tyr-Octreotide , ¹³¹I-Tyr-Octreotide was prepare for chloramine-T method and find out the optimal reaction condition, the radiochemical purity and colloid content were measured;kill the mice at differents time, determine the radiocounting of blood and organs, and take out the %ID/g and studied the biodistribution and metabolism;nude mice bearing human NSCLC model was established, and were divided into three groups to observe the radioactive uptake ,one group was injected ¹³¹I-Tyr-Octreotide through tail vein,the other two groups were injected ¹³¹I-Tyr-Octreotide and ¹³¹I through stroma,The radioactivity ratio of tumor to normal tissue (T/NT) was calculated over ROI , checked with SPECT to observe the radioactive uptake,the tumor cell cycle and cell apoptosis were analyzed by FCM,TUNEL and histopathological as to evaluate the anti-tumor effect on NSCLC by ¹³¹I-Tyr-Octreotide.Results The reaction condition of Ch-T is pH 7.4,0.2mol/L 150μl of PB,Octreotide 10μg,Na¹³¹I(37MBq)0.05 ml,Ch-T 90μg,Na₂S₂O₅ 120μg,temperature is 25℃and reaction time is 2.5min;The instant radiochemical purity was 95±1.67%,and the radiochemical purity was remaind 83±1.58% after 6h , colloid content is 1.02±0.98 % ;The biodistribution showed high uptake of the tracer in kidney and liver, then the stomach intestine, other organs show low uptake,blood elimination is fast. SPECT show that the radioactive was more higher in group of injected ¹³¹I-Tyr-Octreotide through stroma than the other groups, the persistence time was long, The T/NT was 52.74±0.13 after 24h,which was much higher than that of the other groups (8.90±0.23,6.42±0.02, P<0.05 ) ,the radioactive of injected through tail vein was as more as in group of injected through stroma ;the tumor cell cycle show that the G1 stage was hold most in group of injected through stroma than the other groups (83.17±7.83,57.02±11.71, 54.29±12.33,P<0.05) ,Apoptosis cells were observed by TUMEL, also have apoptotic body.Conclusion Tyr-Octreotide was easily to be labeled by chloramine-T,It has achieved high radio-labelling ratio and is a convenient and fast methods.Lower uptake in liver and spleen ,it was quickly cleared from blood and has a high target to tumor that express SSTR. ¹³¹I-Tyr-Octreotide could induce tumor apoptosis and inhibit the tumor cell of NSCLC, It may be a promising agent mediated by somatostatin for diagnos and treat of NSCLC ,further study is on the way.