Experimental Study On The Peptides K237Radiolabeled With Iodine-131for Imaging And Targeting Therapy In Nude Mice Bearing Human Prostate Cancer

ObjectiveIn our studies we use the most common radionuclide I-131to label the peptide K237andthen explore the feasibility of the¹³¹I-K237on the imaging and targeting therapy of nudemice bearing human prostate cancer.MethodsIodogen method was used to label the peptide K237. The labeling rate and radiochemicalpurity were measured by the TLC method to get the¹³¹I-K237injection whose labeling ratewas greater than95%.The human prostate cancer cell lines LNCap were cultured and the nudemice bearing human prostate cancer were built. Follow studies have benn done:（1） Thebiological distribution of the¹³¹I-K237in nude mice bearing human prostate cancer LNCap:35mouse with diameter of tumors over0.7cm were randomly selected and executed at30min,1h,2h,4h,8h,12h and24h after the tail vein injection of¹³¹I-K2372.96Mbq.Thepercentage activity of injection dose per gram of the tumor and other organs were measured.（2）The dynamic metabolism of¹³¹I-K237in normal rabbit:3rabbits were taken imageimmediately after the injection of¹³¹I-K23711.1MBq via ear vein. One frame was taken perminute for60minutes and the results were managed by computer. The static imaging wastaken at90minutes and120minutes after the injection to further study the metabolism of¹³¹I-K237in rabbit.（3）The imaging of¹³¹I-K237in nude mouse bearing human prostatecancer:5mouse with diameter of tumors over0.7cm were randomly selected and imaged bySPECT/CT at1h,2h,4h,8h after the injection of¹³¹I-K2375.55Mbq to study the optimumimaging time.（4）The targeting therapy of¹³¹I-K237in nude mice bearing human prostate cancer:24mouse with diameter of tumors over0.7cm were divided into three groupsrandomly including the physiological saline group，K237group and¹³¹I-K237group. Themouse in each group were injected with physiological saline （0.1ml）, K237（40μg） and¹³¹I-K237（11.1Mbq,40μg）, respectively. The diameter of the tumor was measured every3day for28days and curves of tumor volume correlative with time were obtained.SPECTimaging of the three groups was performed at3d,7d,14d and28d after the injection ofcorresponding reagents.The effect of the¹³¹I-K237on prostate cancer was verified by themeasure of the tumor volume and the imaging of the tumor at particular time.Results（1） The results of the biological distribution of the¹³¹I-K237in nude mice bearing humanprostate cancer showed that the uptake of the radioactive reagent by tumor was highest at30min after injection.The T/NT ratios increased with time and were2.08±0.15、2.28±0.10、2.45±0.13、2.68±0.18、3.04±0.26、3.97±0.26,4．41±0.33at30min,1h,2h,4h,8h,12h and24h, respectively.（2）The normal biodistribution of¹³¹I-K237in rabbit showed relatively highaccumulation in the liver, kidneys and bladder. With the time the uptakes of liver and kidneyswere decreased and uptake in the bowel can be seen. The static imaging showed only boweland bladder still can be seen clearly at90min after injection and the uptakes of all organs werelittle except the bladder at120min after the injection.（3） The SPECT imaging of¹³¹I-K237innude mouse bearing human prostate cancer showed that the tumor can be seen faintly at1hafter the injection of¹³¹I-K237. With the time the uptake of the tumor was increased and thetumor became distinct at4h after the injection.The tumor/muscle ratios were4.42±0.36.（4）The average tumor volume in group¹³¹I-K237,K237and physiological saline were0.61cm3、1.03cm3、1.82cm3. The average tumor volume of the mouse in groups¹³¹I-K237were significantly smaller than that in others. The inhibition rate of the group¹³¹I-K237andK237was69.01%and45.91%.The SPECT imaging showed that the volume and the uptakeof the¹³¹I-K237in group¹³¹I-K237was smaller. Conclusion（1）The¹³¹I-K237is excreted in kidneys and the tumor of nude mice bearing humanprostate cancer can uptake the¹³¹I-K237with the time.（2）¹³¹I-K237can be uptake specific byprostate cancer so that may become a potential tracer for the prostate cancer.（3）¹³¹I-K237hasa significant effect on the therapy of the nude mice bearing human prostate cancer and has thepotential of clinical use for prostate cancer therapy.