Preparation of HER2 radioligand 99Tcm-ABH2 and its in vivo imaging in breast cancer-xenografted mice / 中华核医学与分子影像杂志

ABSTRACT

Objective To prepare 99Tcm-human epidermal growth factor receptor 2 (HER2) affibody (ABH2) and explore its feasibility as an imaging agent in HER2-positive breast cancer.Methods Sodium glucoheptonate and SnCl2 · 2H2O were used to label ABH2 with 99Tcm.The labeling yield and radiochemical purity of 99Tcm-ABH2 were determined.The stability of 99Tcm-ABH2 was tested in PBS and serum.The equilibrium disassociation constant (Kd) of 99Tcm-ABH2 was measured with MBA-MD-361 breast cancer cells.SPECT/CT imaging was carried out at 1.0 h and 4.5 h after injection of 37 MBq 99Tcm-ABH2 in nude mice (n=4) xenografted with MBA-MD-361 breast cancer.The T/NT (liver,brain,lung,heart,bone and muscle) ratios were deduced from SPECT/CT acquired data.For the blocking experiment,200 μg ABH2 was injected intravenously before 99Tcm-ABH2 injection.SPECT/CT imaging was performed in the same way.The T/NT ratios were compared between non-blocked and blocked groups by one-way analysis of variance.Results Fhe labeling yield of 99Tcm-ABH2 was above 99％.99Tcm-ABH2 was substantially stable in PBS and serum;the radiochemical purity was (95.0± 1.0)％ after incubation with serum at 37 ℃ for 6.0 h.The Kd of 99Tcm-ABH2 was 1.7 nmol/L.The radioactive uptake in cancer was visualized at 1.0 h and 4.5 h after injection of 99Tcm-ABH2 in HER2 positive MDA-MB-361 breast cancer.99Tcm-ABH2 was cleared out mainly through urinary system.The ratios of tumor to liver,lung,brain,heart,muscle and bone were 1.81± 0.60,8.95±1.13,20.08±6.12,7.61±0.56,10.62±1.78,11.42±2.07,respectively at 4.5 h after 99Tcm-ABH2 injection.After ABH2 blocking,the corresponding T/NT ratios were 0.60±0.23,3.05± 1.38,5.24±2.17,2.42±1.02,8.16±2.66,2.76±0.48 (F=29.38,P＜0.05) respectively.Conclusion 99Tcm-ABH2 could be synthesized with high purity,and this new agent could be used to image HER2-positive breast cancer specifically.