Author/Authors :
Zhang, Dongjian Nanjing University of Chinese Medicine - Nanjing, China , Gao, Meng Nanjing University of Chinese Medicine - Nanjing, China , Yao, Nan Nanjing University of Chinese Medicine - Nanjing, China , Jiang, Cuihua Nanjing University of Chinese Medicine - Nanjing, China , Liu, Wei Department of Nuclear Medicine - The First Affiliated Hospital of Nanjing Medical University - Nanjing, China , Li, Tiannv Department of Nuclear Medicine - The First Affiliated Hospital of Nanjing Medical University - Nanjing, China , Song, Shaoli Department of Nuclear Medicine - Renji Hospital - Shanghai Jiaotong University School of Medicine - Shanghai, China , Huang, Dejian Nanjing University of Chinese Medicine - Nanjing, China , Yin, Zhiqi Department of Natural Medicinal Chemistry and Jiangsu Key Laboratory of Natural Medicines - China Pharmaceutical University - Nanjing, China , Qiu, Yunliang Department of Criminal Science and Technology - Nanjing Forest Police College - Nanjing, China , Jin, Qiaomei Nanjing University of Chinese Medicine - Nanjing, China
Abstract :
This study aimed to explore the use of 131I-Hoechst 33258 (131I-H33258) for early prediction of tumor response to vasculardisrupting agents (VDAs) with combretastatin-A4 phosphate (CA4P) as a representative. Necrosis avidity of 131I-H33258 was
evaluated in mouse models with muscle necrosis and blocking was used to confrm the tracer specifcity. Therapy response was
evaluated by 131I-H33258 SPECT/CT imaging 24 h after CA4P therapy in W256 tumor-bearing rats. Radiotracer uptake in tumors
was validated ex vivo using y-counting, autoradiography, and histopathological staining. Results showed that 131I-H33258 had
predominant necrosis avidity and could specifcally bind to necrotic tissue. SPECT/CT imaging demonstrated that an obvious “hot
spot” could be observed in the CA4P-treated tumor. Ex vivo y-counting revealed 131I-H33258 uptake in tumors was increased 2.8-
fold in rats treated with CA4P relative to rats treated with vehicle. Autoradiography and corresponding H&E staining suggested
that 131I-H33258 was mainly localized in necrotic tumor area and the higher overall uptake in the treated tumors was attributed
to the increased necrosis. These results suggest that 131I-H33258 can be used to image induction of cell necrosis 24 h after CA4P
therapy, which support further molecular design of probes based on scaffold H33258 for monitoring of tumor response to VDAs
treatment.
