Radiosynthesis and evaluation of N5-(2-18F-fluoropropanyl) ornithine as a potential agent for tumor PET imaging

Wang, Hongliang; Zhao, Qinan; Dong, Weixuan; Liu, Yang; Lü, Kun; Guo, Xiaoshan; Liu, Haiyan; Wei, Hua; Cheng, Yan; Wu, Zhiyong; Li, Sijin

doi:10.1016/j.nucmedbio.2021.02.002

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Both processes would be disadvantageous for imaging by PET. In contrast, the 2-[ 18 F]fluoropropanoyl group is used frequently for PET tracer design, due to higher metabolic stability [ 44 , 45 , 46 , 47 ]. Additionally, it is expected to have a low impact on biological activity due to its small size.…”

Section: Resultsmentioning

confidence: 99%

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

et al. 2022

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The degree of acetylation of lysine residues on histones influences the accessibility of DNA and, furthermore, the gene expression. Histone deacetylases (HDACs) are overexpressed in various tumour diseases, resulting in the interest in HDAC inhibitors for cancer therapy. The aim of this work is the development of a novel 18F-labelled HDAC1/2-specific inhibitor with a benzamide-based zinc-binding group to visualize these enzymes in brain tumours by positron emission tomography (PET). BA3, exhibiting high inhibitory potency for HDAC1 (IC50 = 4.8 nM) and HDAC2 (IC50 = 39.9 nM), and specificity towards HDAC3 and HDAC6 (specificity ratios >230 and >2080, respectively), was selected for radiofluorination. The two-step one-pot radiosynthesis of [18F]BA3 was performed in a TRACERlab FX2 N radiosynthesizer by a nucleophilic aliphatic substitution reaction. The automated radiosynthesis of [18F]BA3 resulted in a radiochemical yield of 1%, a radiochemical purity of >96% and a molar activity between 21 and 51 GBq/µmol (n = 5, EOS). For the characterization of BA3, in vitro and in vivo experiments were carried out. The results of these pharmacological and pharmacokinetic studies indicate a suitable inhibitory potency of BA3, whereas the applicability for non-invasive imaging of HDAC1/2 by PET requires further optimization of the properties of this compound.

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Section: Resultsmentioning

confidence: 99%

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

et al. 2022

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A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors

et al. 2023

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Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) to produce amounts of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68 Ga-labeled ornithine analog ( 68 Ga-NOTA-Orn). The synthesis time of 68 Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. 68 Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of 68 Ga-NOTA-Orn was similar to that of Lornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micropositron emission tomography (Micro-PET) imaging studies showed that 68 Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that 68 Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

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A new 68Ga-labeled ornithine for tumor ornithine metabolism PET imaging

Wang

Qin

Shi

et al. 2022

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Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) to produce amounts of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68Ga-labeled ornithine analog (68Ga-NOTA-Orn). The synthesis time of 68Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45–50% (uncorrected), and the radiochemical purity was > 98%. 68Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of 68Ga-NOTA-Orn was similar to that of L-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that 68Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that 68Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

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Radiosynthesis and evaluation of N5-(2-18F-fluoropropanyl) ornithine as a potential agent for tumor PET imaging

Cited by 3 publications

References 36 publications

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors

A new 68Ga-labeled ornithine for tumor ornithine metabolism PET imaging

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