Targeting peptide-mediated 131I-polyamidoamine in medullary thyroid carcinoma bearing mice / 中华核医学与分子影像杂志

ABSTRACT

Objective To construct 131 I-the fifth generation polyamidoamine (PAMAM(G5.0)) with targeting peptide Ser-Arg-Glu-Ser-Pro-His-Pro (SRESPHP;SR) or Gly-Pro-Leu-Pro-Leu-Arg (GPLPLR;GP) and double targeting peptide SR/GP,and evaluate the targeting ability in medullary thyroid carcinoma (MTC) model.Methods PAMAM(GS.0),PAMAM(GS.0)-SR,PAMAM(GS.0)-GP and PAMAM(GS.0)-SR/GP were radiolabeled with 131I by chloramine T method.The radiolabeled yield and radiochemical purity were determined by thin layer chromatography.MTC xenografts were developed and the percentage radio-activity of injection dose per gram of tissue (％ID/g) in tumor and organs was measured at 24 h post-injection.Region of interest (ROI) was drawn and the tumor/non-tumor (T/NT) ratios at 4,8 and 24 h post-injection were calculated and compared among different groups.One-way analysis of variance,repetitive measurement analysis of variance and Dunnett-t test were used to compare the data of different groups.The relationship between ％ID/g and T/NT was analyzed with Pearson correlation.Results The radiolabeled yield was more than 75％ and radiochemistry purity was more than 90％.The difference of ％lD/g at 24 h post-injection was significant (F=14.400,P＜0.001) in tumors of all groups.The radioactive uptake in tumor of 131I-PAMAM (G5.0)-SR group was the highest at 24 h post-injection ((1.80± 0.18) ％ID/g).There were significant differences of T/NT ratios among different groups (F =4.776,P＜ 0.05)and between different time points (F =8.630,P＜0.05).Compared with negative control group (Na131 I),the T/NT ratios significantly increased in 131I-PAMAM(G5.0)-SR group at 4,8 and 24 h post-injection (t=4.169,7.123 and 4.032,all P＜0.05) and in 131I-PAMAM(G5.0)-GP group at 4 h post-injection (t =5.893,P＜0.05).The T/NT ratio in 131I-PAMAM (G5.0)-SR group was higher than that in 131 I-PAMAM (G5.0)-GP group at 24 h post-injection (t=2.871,P＜0.05).Conclusions PAMAM(G5.0)-SR,PAMAM(G5.0)-GP and PAMAM(G5.0)-SR/GP can target the MTC models.131I-PAMAM(G5.0)-SR has the best biological properties and may provide a new precision method for MTC diagnosis,treatment and prognosis evaluation.