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  • Title: Preclinical Evaluation of Radioiodinated Hoechst 33258 for Early Prediction of Tumor Response to Treatment of Vascular-Disrupting Agents.
    Author: Zhang D, Gao M, Yao N, Jiang C, Liu W, Li T, Song S, Huang D, Yin Z, Qiu Y, Jin Q.
    Journal: Contrast Media Mol Imaging; 2018; 2018():5237950. PubMed ID: 29681781.
    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.
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