Synthesis of novel PEG-modified nitroimidazole derivatives via “hot-click” reaction and their biological evaluation as potential PET imaging agent for tumors

Cao, Jianhua; Liu, Yajing; Zhang, Lifang; Du, Fenghua; Ci, Yingqian; Zhang, Yan; Xiao, Hong; Yao, Xinyue; Shi, Shengyu; Zhu, Lin; Kung, Hank F.; Qiao, Jie

doi:10.1007/s10967-017-5210-5

Cited by 11 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro cellular uptake of [ 18 F] 5 , [ 18 F] 8 , [ 18 F]FMISO, and 2-[ 18 F]FPA (Figure A–D, respectively) in EMT-6 cells under hypoxic and normoxic conditions was determined according to previous reported methods. − This method of in vitro study has been successfully validated in our laboratory in the evaluation of PEG-modified nitroimidazole derivatives . [ 18 F]FMISO was used as a gold standard for comparison and 2-[ 18 F]FPA as a negative control.…”

Section: Results and Discussionmentioning

confidence: 99%

“…47−49 This method of in vitro study has been successfully validated in our laboratory in the evaluation of PEG-modified nitroimidazole derivatives. 50 [ 18 F]FMISO was used as a gold standard for comparison and 2-[ 18 F]FPA as a negative control. As expected, [ 18 F]FMISO (Figure 2C) showed a significantly greater accumulation in EMT-6 cells after 1 h in hypoxic conditions (P < 0.01), while the uptakes of 2-[ 18 F]FPA (Figure 2D) displayed no difference between hypoxic cells and normoxic cells (P > 0.05).…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia

et al. 2019

Self Cite

View full text Add to dashboard Cite

Hypoxia is an important biochemical and physiological condition associated with uncontrolled growth of tumor. Measurement of hypoxia in tumor tissue may be useful in characterization of tumor progression and monitoring drug treatment.[ 18 F]FMISO is the most widely employed radiotracer for imaging of hypoxic tissue with positron emission tomography (PET). However, it showed relatively low uptake in hypoxic tissues, which led to low target-to-background contrast in PET images. To overcome these shortcomings, two novel 2-fluoroproprioic acid esters, nitroimidazole derivatives 2-fluoropropionic acid 2-(2nitro-imidazol-1-yl)-ethyl ester (FNPFT, [ 19 F]5) and 2-fluoropropionic acid 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester (FMNPFT, [ 19 F]8), were prepared and tested. Radiolabeling of [ 18 F]5 and [ 18 F]8 was accomplished in 45 min (radiochemical purity >95%, the decay-corrected radiochemical yield of [ 18 F]5 was 11 ± 2%, and that of [ 18 F]8 was 13 ± 2%, n = 5). In vitro cell uptake studies using EMT-6 tumor cells showed that both radiotracers [ 18 F]5 and [ 18 F]8 displayed significantly higher uptake in hypoxic cells than those under normoxic condition, while 2-[ 18 F]fluoropropionic acid (2-[ 18 F]FPA) displayed no difference. Biodistribution studies in mice bearing EMT-6 tumor showed that [ 18 F]5, [ 18 F]8, and 2-[ 18 F]FPA displayed similar tumor and major organ uptakes. Tumor uptake values for all three agents were higher than those of [ 18 F]FMISO, respectively (P < 0.05). This is likely due to a rapid in vivo hydrolysis of [ 18 F]5 and [ 18 F]8 to their metabolite, 2-[ 18 F]FPA. Micro PET imaging studies in the same EMT-6 implanted mice tumor model also demonstrated that both [ 18 F]5 and [ 18 F]8 displayed similar tumor uptake comparable to that of 2-[ 18 F]FPA. In conclusion, two new fluorine-18 labeled nitroimidazole derivatives, [ 18 F]5 and [ 18 F]8, showed good tumor uptakes in mice bearing EMT-6 tumor. However, in vivo biodistribution results suggested that they were more likely reflect the predominance of in vivo produced metabolite, 2-[ 18 F]FPA, which may not be related to tumor hypoxic condition.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The precursor, radioactive [ 125/131 I]ITE2 and non‐radioactive [ 127 I]ITE2 were synthesized according to the previously reported references (Cao et al., 2017; Ji, Zhou, Qian, & Chen, 2014; Li, Zhang, Zhu, & Zhang, 2008; Liu et al., 2014; Moldovan et al., 2016). The specific steps are available in Scheme 1 and supplementary information.…”

Section: Methodsmentioning

confidence: 99%

Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

Peng

Gao

et al. 2020

Chem Biol Drug Des

View full text Add to dashboard Cite

The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy) ethyl)-5-[ 125/131 I]iodo-1,2,3-triazole-diestradiol ([ 125/131 I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [ 125/131 I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [ 125/131 I]ITE2 had good stability in vitro and moderate molar activity (0.3 ± 0.2 GBq/µmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [ 131 I]ITE2 had high uptake in ERabundant uterine and ovarian (5.7 ± 0.4 and 10.1 ± 1.4%ID/g at 1 hr postinjection) and could be blocked by co-injection of estradiol (2.7 ± 0.1 and 5.5 ± 0.4%ID/g) obviously. In the SPECT/CT imaging study, [ 125 I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1 ± 0.4%ID/g) than that of MDA-MB-231 (0.9 ± 0.1%ID/g). Furthermore, the specific uptake of [ 125 I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2 ± 0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis.

show abstract

“…The rapid and uncontrollable tumour growth prevents the build-up of an adequate blood vascular structure causing deprivation of nutrients and oxygen in deeper areas. The resistance of hypoxic areas to both radio-and chemotherapy is the main factor in poor prognosis and cancer recurrence [5,6].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterisation of a Boron-Rich Symmetric Triazine Bearing a Hypoxia-Targeting Nitroimidazole Moiety

et al. 2021

View full text Add to dashboard Cite

Boron Neutron Capture Therapy (BNCT) is a binary therapy that promises to be suitable in treating many non-curable cancers. To that, the discovery of new boron compounds able to accumulate selectively in the tumour tissue is still required. Hypoxia, a deficiency of oxygen in tumor tissue, is a great challenge in the conventional treatment of cancer, because hypoxic areas are resistant to conventional anticancer treatments. 2-Nitroimidazole derivatives are known to be hypoxia markers due to their enrichment by bioreduction in hypoxic cells. In the present work, 2-nitroimidazole was chosen as the starting point for the synthesis of a new boron-containing compound based on a 1,3,5-triazine skeleton. Two o-carborane moieties were inserted to achieve a high ratio of boron on the molecular weight, exploiting a short PEG spacer to enhance the polarity of the compound and outdistance the active part from the core. The compound showed no toxicity on normal human primary fibroblasts, while it showed noteworthy toxicity in multiple myeloma cells together with a consistent intracellular boron accumulation.

show abstract

Synthesis of novel PEG-modified nitroimidazole derivatives via “hot-click” reaction and their biological evaluation as potential PET imaging agent for tumors

Cited by 11 publications

References 33 publications

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia

Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

Synthesis and Characterisation of a Boron-Rich Symmetric Triazine Bearing a Hypoxia-Targeting Nitroimidazole Moiety

Contact Info

Product

Resources

About