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27.06.2019 | Research Article

Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis

verfasst von: Aimi Zhang, Tianze Wu, Li Bian, Panli Li, Qiufang Liu, Dongjian Zhang, Qiaomei Jin, Jian Zhang, Gang Huang, Shaoli Song

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2020

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Abstract

Purpose

This study aimed to synthesize a necrosis-avid agent using rhein as a precursor and labeled with gallium-68 (Ga-68) for positron emission tomography/computed tomography (PET/CT) imaging, to evaluate response to anticancer treatment in a mouse model.

Procedures

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)–conjugated rhein was radiolabeled with Ga-68 to formulate [⁶⁸Ga]DOTA-rhein. The in vitro stability of [⁶⁸Ga]DOTA-rhein was assessed by radio-HPLC. Necrosis avidity was evaluated in a mouse model of muscle necrosis by microPET/CT imaging, biodistribution study, histochemical staining, and autoradiography studies. Murine tumor models with the subcutaneous implantation of S180 cell lines were generated for the evaluation of therapeutic effect. Tumor necrosis was induced by the treatment of combretastatin A4 disodium phosphate (CA4P), and microPET/CT imaging was performed at 1 h post tracer injection. DNA binding studies were conducted to explore the necrosis avidity mechanism of the tracer.

Results

[⁶⁸Ga]DOTA-rhein exhibited a satisfactory yield, a radiochemical purity over 97 %, and a good serum stability. The uptakes of [⁶⁸Ga]DOTA-rhein in necrotic muscles and tumors were significantly higher than those in normal muscles and tumors (P < 0.05). The results of autoradiography and histochemical staining were consistent with the selective uptake of the radiotracer in necrotic regions. MicroPET/CT images showed a high uptake of the tracer in necrotic muscles and necrotic tumors. DNA binding studies suggested that necrosis avidity correlated with DNA binding to a certain extent.

Conclusions

Our results demonstrated that [⁶⁸Ga]DOTA-rhein showed a prominent necrosis avidity and could be a useful probe for early assessment of response to anticancer therapy by PET/CT imaging.

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Titel: Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis
verfasst von: Aimi Zhang
Tianze Wu
Li Bian
Panli Li
Qiufang Liu
Dongjian Zhang
Qiaomei Jin
Jian Zhang
Gang Huang
Shaoli Song
Publikationsdatum: 27.06.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01365-y

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Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis

Abstract

Purpose

Procedures

Results

Conclusions

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Abstract

Purpose

Procedures

Results

Conclusions

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