Anti-tumor Effect Of Polypeptide ¹³¹I-K237 To NSCLC Bearing Nude Mice Model

【Objective】The feasibility of 131I label polypeptide K237 and the distribution of the labeled production in mice, as well as 131I-K237 inhibit tumors effect for non-small cell lung cancer nude mice model meanwhile observe toxic-side effect.【Methods】131I labeled to K237 through Iodogen method, to separate and purify the production with Sephadex G25 pillar, and exam stability; find out its biological activity by MTT method to detect the effect of 131I-K237 production inhibit HUVEC proliferate; by mice tails veins infuse 150μCi 131I-K237 to observe 131I-K237 biological distribution; implant lung adenocarcinoma cell A549 as well as built BALB/c tumor nude mice models; 32 lung adenocarcinoma A549 nude mice models, 12 to exam T/NT, the other 20 were divided four groups at random(5 each group) when the diameter is about 0.7cm: physiological saline control group, K237 treat group, Na131I treat group and 131I-K237 treat group, each group infuse 0.15ml, dosage 300μCi each mouse refer to relevant documents, repeat infuse once after 7 days, and K237 group dosage is 150μg/once/2d, kill all nuke mice after 30 days, compare tumors volume, calculate restrain tumor rate, draw tumors grow curved shape; choose partial tumors tissues to observe microcosmic index (HE stain, immunohistochemistry stain, electron microscope detect and PCR proliferate target aim VEGFR gene); to take the killed nake mice blood, heart, liver and kidney tissues and so on to carry out blood routine and liver renal function inspect, meanwhile pathology inspect to observe radioactivity toxic-side effect; apply SAS 8.0 medical statistics software, if normal distribution to use t-test between two groups, use variance analysis in several groups comparison, and P>0.05 have not statistically significant, P<0.05 have statistically significant. 【Results】131I-K237 labeled rate is about 69%, detect radioactivity chemical purity after Sephadex G25 pillar separate and purify the production is above 95%, specific activity is 0.18 MBq·μg-1, polypeptide 131I-K237 37℃preserved brood 24 hours with the same volume mice serum, its radioactivity chemical purity still to remain above 90%; the effect of 131I-K237 inhibit HUVEC cell proliferate is obvious.Several times points detect several organs radioactive counting per minute(cpm) after mice tails veins infusion, count per gramme tissue percent inject dose rate(%ID/g), may to realize kidney %ID/g is the highest in 30 min, is up to 118.9±2.73 (%ID/g). With times progress, the radioactivity of each organs is fade; kidney radioactivity is 68.4±1.72 (%ID/g) after 1 hour and is down to 33.0±1.61 (%ID/g) after 3 hours, the number is 3.39±1.16 (%ID/g) after 12 hours. The radioactivity of blood is 19.20±2.42 (%ID/g) after 30 min and is down to 8.52±1.11 (%ID/g) after 3 hours, the number is 0.79±0.05 (%ID/g) after 12 hours. When the tumors size in 12 nake mice models is accord with study need, to do 131I-K237 distribution and tumor/non-tumor (T/NT) radioactivity ratio, the choose time points are 3 hours, 6 hours, 12 hours and 24 hours, result display tumors/muscle (T/NT) is the highest when time point is 24 hours and the ratio is up to 9.92, meanwhile 12 hours is 7.12.When treat study is over, compare 131I-K237 group, K237 group with physiological saline group, two treat groups tumors volume are different for physiological group, statistic show statistics significant(P<0.05), their restrain tumor rate are 76.95% and 53.35% respective; there is t testing between physiological saline group and Na131I group, result P>0.05, statistic show not statistically significant. Through correlative microcosmic index inspect, to know 131I-K237 group and K237 group tumors microvessels density decrease, tumors cells necrosis are very obvious, intra-cell have many vacuole structure, core pyknosis, core karyorrhexis phenomenon common. After treat to exam blood regulation, liver-renal function and relative tissue pathology, but the result are normal, so the study dosage have obvious not toxic-side effect.【Conclusions】131I-K237 is easy prepared, have high labeled rate and good stability, the biological activity do not revise, and have favourable biological distribution feature, fast clean in blood, few effect for blood constituent, have obvious effect to restrain tumors growth for lung cancer models, and the study dosage is safe, so 131I-K237 may be ideal anti-tumor drug and ideal tumor imaging agent.