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Contrast Media & Molecular Imaging
Volume 2018, Article ID 5237950, 9 pages
https://doi.org/10.1155/2018/5237950
Research Article

Preclinical Evaluation of Radioiodinated Hoechst 33258 for Early Prediction of Tumor Response to Treatment of Vascular-Disrupting Agents

1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
2Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
3Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
4Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
5Department of Natural Medicinal Chemistry and Jiangsu Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
6Department of Criminal Science and Technology, Nanjing Forest Police College, Nanjing 210023, China

Correspondence should be addressed to Yunliang Qiu; nc.ude.cpfn@lyuiq and Qiaomei Jin; moc.361@yxmqj

Received 2 August 2017; Revised 17 October 2017; Accepted 4 December 2017; Published 26 February 2018

Academic Editor: Giancarlo Pascali

Copyright © 2018 Dongjian Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed to explore the use of 131I-Hoechst 33258 (131I-H33258) for early prediction of tumor response to vascular-disrupting 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 confirm the tracer specificity. 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 γ-counting, autoradiography, and histopathological staining. Results showed that 131I-H33258 had predominant necrosis avidity and could specifically bind to necrotic tissue. SPECT/CT imaging demonstrated that an obvious “hot spot” could be observed in the CA4P-treated tumor. Ex vivo γ-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.