Preparation of an estrogen receptor SPECT imaging agent 99Tcm-GAP-EDL and its preliminary study in breast tumor-bearing nude mice / 中华核医学与分子影像杂志

ABSTRACT

Objective To prepare a kind of 99Tcm-labeled estrogen receptor (ER) SPECT imaging agent,and evaluate its binding characteristics with ER by in vitro and in vivo studies.Methods EDL was prepared from estrone and then reacted with GAP to synthesize GAP-EDL.Then,GAP-EDL was labeled with 99Tcm to obtain 99Tcm-GAP-EDL.Cell uptake and blocking assays were performed in vitro on MCF-7and MDA-MB-231 cells.The biodistribution study of 99Tcm-GAP-EDL was performed on normal BALB/c mice at 30,60,120,180 and 240 min post injection.Nude mice bearing either MCF-7 or MDA-MB-231derived tumors were injected with 99Tcm-GAP-EDL,and subjected to γimaging at 1,2,4 h post injection.The mice injected with excess unlabeled GAP-EDL or estradiol were used as the blocking control.Two-sample t test was used for data analysis.Results The radiolabeling yield of 99Tcm-GAP-EDL was (98.8 ±0.5) ％ and the radiochemical purity after 24 h was over 90％.The cell uptake rate of MCF-7 cells at 240min was (4.84± 0.21) ％,which was significantly higher than that of MDA-MB-231 cells ((2.11±0.21) ％;t =15.96,P＜0.05).99 Tcm-GAP-EDL uptake rate of MCF-7 cells in blocking groups ((2.31 ± 0.28) ％ and (2.05±0.35) ％) decreased significantly compared to that of non-blocking group(t=11.52,11.16,both P＜0.05).Biodistribution studies showed that 99Tcm-GAP-EDL was mainly metabolized by the liver and kidneys,and exhibited quick blood clearance.Gamma imaging showed high uptake in MCF-7 tumors 1 h post injection and the uptake reached the highest at 4 h,while there was little 99Tcm-GAP-EDL uptake in MDA-MB231 tumors and blocked MCF-7 tumors.Conclusions 99Tcm-GAP-EDL may be prepared under mild conditions with high labeling purity and stability.The in vitro and in vivo characteristics of 99Tcm-GAP-EDL suggest that it may be a promising probe for ER positive tumor imaging.