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Molecular Imaging and Biology

Erschienen in:

18.10.2018 | Research Article

SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein

verfasst von: Jiajia Liang, Qi Luo, Dongjian Zhang, Qiaomei Jin, Lichao Liu, Wei Liu, Meng Gao, Jian Zhang, Zhiqi Yin

Erschienen in: Molecular Imaging and Biology | Ausgabe 4/2019

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Abstract

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 [^99mTc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment.

Procedures

In vitro necrosis avidity of [^99mTc]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 [^99mTc]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 [^99mTc]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

[^99mTc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.

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Titel: SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein
verfasst von: Jiajia Liang
Qi Luo
Dongjian Zhang
Qiaomei Jin
Lichao Liu
Wei Liu
Meng Gao
Jian Zhang
Zhiqi Yin
Publikationsdatum: 18.10.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 4/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1285-9

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SPECT Imaging of Treatment-Related Tumor Necrosis Using Technetium-99m-Labeled Rhein