使用锝-99m 标记的雷因行 SPECT 成像观察治疗相关的肿瘤坏死。
SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein.
机构信息
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu Province, People's Republic of China.
Department of TCMs Pharmaceuticals & State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No.24, Tongjiaxiang, Gulou District, Nanjing, 210009, Jiangsu Province, People's Republic of China.
出版信息
Mol Imaging Biol. 2019 Aug;21(4):660-668. doi: 10.1007/s11307-018-1285-9.
PURPOSE
Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment.
PROCEDURES
In vitro necrosis avidity of [Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission-computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining.
RESULTS
The uptake of [Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells (p < 0.05). SPECT/CT imaging showed that an obvious "hot spot" was observed in the CA4P-treated tumor while not in the control tumor at 5 h after tracer injection. Ex vivo γ-counting revealed that the uptake of [Tc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues.
CONCLUSION
[Tc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.
目的
治疗诱导性坏死的无创成像对于将早期应答者与对治疗方案有抗性的患者区分开来非常重要，从而实现定制化的治疗干预。本研究旨在探索 [Tc]EDDA-HYNIC-2C-rhein 用于早期评估肿瘤对治疗反应的可行性。
方法
在接受热疗的人肺癌 A549 细胞中评估 [Tc]EDDA-HYNIC-2C-rhein 的体外坏死亲和力。在接受 CA4P 治疗的皮下 W256 肿瘤荷瘤大鼠和接受单次微波消融治疗的原位肝 W256 肿瘤荷瘤大鼠中进行单光子发射计算机断层扫描/X 射线计算机断层扫描（SPECT/CT）成像。所有大鼠均在成像后立即安乐死，进行生物分布和组织学研究。通过体内阻断实验、体外组织化学和荧光染色进一步探讨了示踪剂的坏死亲和力机制。
结果
坏死细胞中 [Tc]EDDA-HYNIC-2C-rhein 的摄取明显高于活细胞（p<0.05）。SPECT/CT 成像显示，在示踪剂注射后 5 小时，CA4P 治疗的肿瘤中观察到明显的“热点”，而对照肿瘤中则没有。离体γ计数显示，与对照组相比，CA4P 治疗组大鼠肿瘤对 [Tc]EDDA-HYNIC-2C-rhein 的摄取增加了 3.5 倍。放射性自显影和相应的 H&E 染色表明，治疗肿瘤中总放射性示踪剂摄取增加归因于坏死增加。用未标记的 HYNIC-2C-rhein 进行阻断实验表明，放射性示踪剂与坏死组织的特异性结合。放射性自显影和组织化学染色以及 PI 荧光染色的完美匹配表明，示踪剂的坏死亲和力可能归因于与坏死组织中暴露的 DNA 插入。
结论
[Tc]EDDA-HYNIC-2C-rhein 可以对抗癌治疗诱导的坏死进行成像，并且有可能用于早期评估治疗反应。
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