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2353 KiB

Open AccessArticle

Optimized and Automated Radiosynthesis of [¹⁸F]DHMT for Translational Imaging of Reactive Oxygen Species with Positron Emission Tomography

by Wenjie Zhang, Zhengxin Cai, Lin Li, Jim Ropchan, Keunpoong Lim, Nabil E. Boutagy, Jing Wu, John C. Stendahl, Wenhua Chu, Robert Gropler, Albert J. Sinusas, Chi Liu and Yiyun Huang

Molecules 2016, 21(12), 1696; https://doi.org/10.3390/molecules21121696 - 9 Dec 2016

Cited by 20 | Viewed by 5649

Abstract

Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these [...] Read more.

Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [¹⁸F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([¹⁸F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [¹⁸F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/µmol (n = 2). Fully automated radiosynthesis of [¹⁸F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/µmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[¹⁸F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [¹⁸F]DHMT was successfully tested for PET imaging in a healthy beagle dog. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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10698 KiB

Open AccessArticle

Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

by Jie Xiao, Xiaobo Xu, Xiao Li, Yanli Li, Guobing Liu, Hui Tan, Hua Shen, Hongcheng Shi and Dengfeng Cheng

Molecules 2016, 21(10), 1308; https://doi.org/10.3390/molecules21101308 - 30 Sep 2016

Cited by 11 | Viewed by 6130

Abstract

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong [...] Read more.

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after ¹⁸⁸ReO₄⁻ or ¹⁸⁸Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the ¹⁸⁸Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the ¹⁸⁸Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, ¹⁸⁸Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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11739 KiB

Open AccessArticle

Molecular-Based Fluorescent Nanoparticles Built from Dedicated Dipolar Thienothiophene Dyes as Ultra-Bright Green to NIR Nanoemitters

by Cristiano Mastrodonato, Paolo Pagano, Jonathan Daniel, Michel Vaultier and Mireille Blanchard-Desce

Molecules 2016, 21(9), 1227; https://doi.org/10.3390/molecules21091227 - 14 Sep 2016

Cited by 21 | Viewed by 6430

Abstract

Fluorescent Organic Nanoparticles (FONs), prepared by self-aggregation of dedicated dyes in water, represent a promising green alternative to the toxic quantum dots (QDs) for bioimaging purposes. In the present paper, we describe the synthesis and photophysical properties of new dipolar push-pull derivatives built [...] Read more.

Fluorescent Organic Nanoparticles (FONs), prepared by self-aggregation of dedicated dyes in water, represent a promising green alternative to the toxic quantum dots (QDs) for bioimaging purposes. In the present paper, we describe the synthesis and photophysical properties of new dipolar push-pull derivatives built from thieno[3,2-b]thiophene as a π-conjugated bridge that connects a triphenylamine moiety bearing various bulky substituents as electron-releasing moiety to acceptor end-groups of increasing strength (i.e., aldehyde, dicyanovinyl and diethylthiobarbiturate). All dyes display fluorescence properties in chloroform, which shifts from the green to the NIR range depending on the molecular polarization (i.e., strength of the end-groups) as well as a large two-photon absorption (TPA) band response in the biological spectral window (700–1000 nm). The TPA bands show a bathochromic shift and hyperchromic effect with increasing polarization of the dyes with maximum TPA cross-section reaching 2000 GM for small size chromophore. All dyes are found to form stable and deeply colored nanoparticles (20–45 nm in diameter) upon nanoprecipitation in water. Although their fluorescence is strongly reduced upon aggregation, all nanoparticles show large one-photon (up to 10⁸ M⁻¹·cm⁻¹ in the visible region) and two-photon (up to 10⁶ GM in the NIR) brightness. Interestingly, both linear and non-linear optical properties are significantly affected by interchromophoric interactions, which are promoted by the molecular confinement and modulated by both the dipolar strength and the presence of the bulky groups. Finally, we exploited the photophysical properties of the FONs to design optimized core-shell nanoparticles built from a pair of complementary dipolar dyes that promotes an efficient core-to-shell FRET process. The resulting molecular-based core-shell nanoparticles combine large two-photon absorption and enhanced emission both located in the NIR spectral region, thanks to a major amplification (by a factor of 20) of the core fluorescence quantum yield. These novel nanoparticles, which combine huge one-and two-photon brightness, hold major promise for in vivo optical bioimaging. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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4577 KiB

Open AccessArticle

LC-MS Supported Studies on the in Vitro Metabolism of both Enantiomers of Flubatine and the in Vivo Metabolism of (+)-[¹⁸F]Flubatine—A Positron Emission Tomography Radioligand for Imaging α4β2 Nicotinic Acetylcholine Receptors

by Friedrich-Alexander Ludwig, René Smits, Steffen Fischer, Cornelius K. Donat, Alexander Hoepping, Peter Brust and Jörg Steinbach

Molecules 2016, 21(9), 1200; https://doi.org/10.3390/molecules21091200 - 8 Sep 2016

Cited by 9 | Viewed by 6518

Abstract

Both enantiomers of [¹⁸F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo [...] Read more.

Both enantiomers of [¹⁸F]flubatine are promising radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). To support clinical studies in patients with early Alzheimer’s disease, a detailed examination of the metabolism in vitro and in vivo has been performed. (+)- and (−)-flubatine, respectively, were incubated with liver microsomes from mouse and human in the presence of NADPH (β-nicotinamide adenine dinucleotide 2′-phosphate reduced tetrasodium salt). Phase I in vitro metabolites were detected and their structures elucidated by LC-MS/MS (liquid chromatography-tandem mass spectrometry). Selected metabolite candidates were synthesized and investigated for structural confirmation. Besides a high level of in vitro stability, the microsomal incubations revealed some species differences as well as enantiomer discrimination with regard to the formation of monohydroxylated products, which was identified as the main metabolic pathway in this assay. Furthermore, after injection of 250 MBq (+)-[¹⁸F]flubatine (specific activity > 350 GBq/μmol) into mouse, samples were prepared from brain, liver, plasma, and urine after 30 min and investigated by radio-HPLC (high performance liquid chromatography with radioactivity detection). For structure elucidation of the radiometabolites of (+)-[¹⁸F]flubatine formed in vivo, identical chromatographic conditions were applied to LC-MS/MS and radio-HPLC to compare samples obtained in vitro and in vivo. By this correlation approach, we assigned three of four main in vivo radiometabolites to products that are exclusively C- or N-hydroxylated at the azabicyclic ring system of the parent molecule. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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949 KiB

Open AccessArticle

Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [¹⁸F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ₁ Receptors

by Mathias Kranz, Bernhard Sattler, Nathanael Wüst, Winnie Deuther-Conrad, Marianne Patt, Philipp M. Meyer, Steffen Fischer, Cornelius K. Donat, Bernhard Wünsch, Swen Hesse, Jörg Steinbach, Peter Brust and Osama Sabri

Molecules 2016, 21(9), 1164; https://doi.org/10.3390/molecules21091164 - 1 Sep 2016

Cited by 31 | Viewed by 7050

Abstract

The enantiomers of [¹⁸F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[¹⁸F]fluspidine and ( [...] Read more.

The enantiomers of [¹⁸F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[¹⁸F]fluspidine and (R)-(+)-[¹⁸F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(−)-[¹⁸F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(−)-[¹⁸F]fluspidine and (R)-(+)-[¹⁸F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(−)-[¹⁸F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [¹⁸F]fluspidine enantiomers determined from the preclinical studies are comparable with other ¹⁸F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(−)-[¹⁸F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(−)-[¹⁸F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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8745 KiB

Open AccessArticle

In Vitro and In Vivo Characterization of Selected Fluorine-18 Labeled Radioligands for PET Imaging of the Dopamine D3 Receptor

by Natascha Nebel, Simone Maschauer, Torsten Kuwert, Carsten Hocke and Olaf Prante

Molecules 2016, 21(9), 1144; https://doi.org/10.3390/molecules21091144 - 29 Aug 2016

Cited by 14 | Viewed by 7260

Abstract

Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled [...] Read more.

Cerebral dopamine D3 receptors seem to play a key role in the control of drug-seeking behavior. The imaging of their regional density with positron emission tomography (PET) could thus help in the exploration of the molecular basis of drug addiction. A fluorine-18 labeled D3 subtype selective radioligand would be beneficial for this purpose; however, as yet, there is no such tracer available. The three candidates [¹⁸F]1, [¹⁸F]2a and [¹⁸F]2b were chosen for in vitro and in vivo characterization as radioligands suitable for selective PET imaging of the D3 receptor. Their evaluation included the analysis of radiometabolites and the assessment of non-specific binding by in vitro rat brain autoradiography. While [¹⁸F]1 and [¹⁸F]2a revealed high non-specific uptake in in vitro rat brain autoradiography, the D3 receptor density was successfully determined on rat brain sections (n = 4) with the candidate [¹⁸F]2b offering a B_max of 20.38 ± 2.67 pmol/g for the islands of Calleja, 19.54 ± 1.85 pmol/g for the nucleus accumbens and 16.58 ± 1.63 pmol/g for the caudate putamen. In PET imaging studies, the carboxamide 1 revealed low signal/background ratios in the rat brain and relatively low uptake in the pituitary gland, while the azocarboxamides [¹⁸F]2a and [¹⁸F]2b showed binding that was blockable by the D3 receptor ligand BP897 in the ventricular system and the pituitary gland in PET imaging studies in living rats. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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4777 KiB

Open AccessArticle

In Vivo Targeted MR Imaging of Endogenous Neural Stem Cells in Ischemic Stroke

by Fang Zhang, Xiaohui Duan, Liejing Lu, Xiang Zhang, Xiaomei Zhong, Jiaji Mao, Meiwei Chen and Jun Shen

Molecules 2016, 21(9), 1143; https://doi.org/10.3390/molecules21091143 - 29 Aug 2016

Cited by 20 | Viewed by 6463

Abstract

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs [...] Read more.

Acute ischemic stroke remains a leading cause of death and disability. Endogenous neurogenesis enhanced via activation of neural stem cells (NSCs) could be a promising method for stroke treatment. In vivo targeted tracking is highly desirable for monitoring the dynamics of endogenous NSCs in stroke. Previously, we have successfully realized in vivo targeted MR imaging of endogenous NSCs in normal adult mice brains by using anti-CD15 antibody-conjugated superparamagnetic iron oxide nanoparticles (anti-CD15-SPIONs) as the molecular probe. Herein, we explore the performance of this molecular probe in targeted in vivo tracking of activated endogenous NSCs in ischemic stroke. Our study showed that intraventricular injection of anti-CD15-SPIONs could label activated endogenous NSCs in situ seven days after ischemic stroke, which were detected as enlarged areas of hypo-intense signals on MR imaging at 7.0 T. The treatment of cytosine arabinosine could inhibit the activation of endogenous NSCs, which was featured by the disappearance of areas of hypo-intense signals on MR imaging. Using anti-CD15-SPIONs as imaging probes, the dynamic process of activation of endogenous NSCs could be readily monitored by in vivo MR imaging. This targeted imaging strategy would be of great benefit to develop a new therapeutic strategy utilizing endogenous NSCs for ischemic stroke. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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6334 KiB

Open AccessArticle

Near-Infrared Emitting PbS Quantum Dots for in Vivo Fluorescence Imaging of the Thrombotic State in Septic Mouse Brain

by Yukio Imamura, Sayumi Yamada, Setsuko Tsuboi, Yuko Nakane, Yoshikazu Tsukasaki, Akihito Komatsuzaki and Takashi Jin

Molecules 2016, 21(8), 1080; https://doi.org/10.3390/molecules21081080 - 18 Aug 2016

Cited by 46 | Viewed by 7722

Abstract

Near-infrared (NIR) fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window) has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging [...] Read more.

Near-infrared (NIR) fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window) has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging at 700–900 nm (first optical window). Here we report lead sulfide (PbS) quantum dots (QDs) and their use for in vivo NIR fluorescence imaging of cerebral venous thrombosis in septic mice. Highly fluorescent PbS QDs with a 1100 nm emission peak (QD1100) were prepared from lead acetate and hexamethyldisilathiane, and the surface of QD1100 was coated with mercaptoundecanoic acid so as to be soluble in water. NIR fluorescence imaging of the cerebral vessels of living mice was performed after intravascular injection (200–300 μL) of QD1100 (3 μM) from a caudal vein. By detecting the NIR fluorescence of QD1100, we achieved non-invasive NIR fluorescence imaging of cerebral blood vessels through the scalp and skull. We also achieved NIR fluorescence imaging of cerebral venous thrombosis in septic mice induced by the administration of lipopolysaccharide (LPS). From the NIR fluorescence imaging, we found that the number of thrombi in septic mice was significantly increased by the administration of LPS. The formation of thrombi in cerebral blood vessels in septic mice was confirmed by enzyme-linked immunosorbent assay (ELISA). We also found that the number of thrombi significantly decreased after the administration of heparin, an inhibitor of blood coagulation. These results show that NIR fluorescence imaging with QD1100 is useful for the evaluation of the pathological state of cerebral blood vessels in septic mice. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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3420 KiB

Open AccessArticle

A Simple and Effective Ratiometric Fluorescent Probe for the Selective Detection of Cysteine and Homocysteine in Aqueous Media

by Risong Na, Meiqing Zhu, Shisuo Fan, Zhen Wang, Xiangwei Wu, Jun Tang, Jia Liu, Yi Wang and Rimao Hua

Molecules 2016, 21(8), 1023; https://doi.org/10.3390/molecules21081023 - 5 Aug 2016

Cited by 25 | Viewed by 6928

Abstract

Biothiols such as cysteine (Cys) and homocysteine (Hcy) are essential biomolecules participating in molecular and physiological processes in an organism. However, their selective detection remains challenging. In this study, ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (NL) was synthesized as a ratiometric fluorescent probe for the [...] Read more.

Biothiols such as cysteine (Cys) and homocysteine (Hcy) are essential biomolecules participating in molecular and physiological processes in an organism. However, their selective detection remains challenging. In this study, ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (NL) was synthesized as a ratiometric fluorescent probe for the rapid and selective detection of Cys and Hcy over glutathione (GSH) and other amino acids. The fluorescence intensity of the probe in the presence of Cys/Hcy increased about 3-fold at a concentration of 20 equiv. of the probe, compared with that in the absence of these chemicals in aqueous media. The limits of detection of the fluorescent assay were 0.911 μM and 0.828 μM of Cys and Hcy, respectively. ¹H-NMR and MS analyses indicated that an excited-state intramolecular proton transfer is the mechanism of fluorescence sensing. This ratiometric probe is structurally simple and highly selective. The results suggest that it has useful applications in analytical chemistry and diagnostics. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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1663 KiB

Open AccessArticle

Synthesis and Evaluation of ^99mTc-Labeled Dimeric Folic Acid for FR-Targeting

by Zhide Guo, Mengna Gao, Manli Song, Changrong Shi, Pu Zhang, Duo Xu, Linyi You, Rongqiang Zhuang, Xinhui Su, Ting Liu, Jin Du and Xianzhong Zhang

Molecules 2016, 21(6), 817; https://doi.org/10.3390/molecules21060817 - 22 Jun 2016

Cited by 28 | Viewed by 7426

Abstract

The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D₁-FA₂) was radiolabeled with [...] Read more.

The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D₁-FA₂) was radiolabeled with ^99mTc using tricine and trisodium triphenylphosphine-3,3′,3″-trisulfonate (TPPTS) as coligands (^99mTc-HYNIC-D₁-FA₂) and its in vitro physicochemical properties, ex vivo biodistribution and in vivo micro-SPECT/CT imaging as a potential FR targeted agent were evaluated. It is a hydrophilic compound (log P = −2.52 ± 0.13) with high binding affinity (IC₅₀ = 19.06 nM). Biodistribution in KB tumor-bearing mice showed that ^99mTc-HYNIC-D₁-FA₂ had high uptake in FR overexpressed tumor and kidney at all time-points, and both of them could obviously be inhibited when blocking with free FA in the blocking studies. From the in vivo micro-SPECT/CT imaging results, good tumor uptake of ^99mTc-HYNIC-D₁-FA₂ was observed in KB tumor-bearing mice and it could be blocked obviously. Based on the results, this new radiolabeled dimeric FA tracer might be a promising candidate for FR-targeting imaging with high affinity and selectivity. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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2304 KiB

Open AccessArticle

A Deoxyuridine-Based Far-Red Emitting Viscosity Sensor

by Mengyuan Wang, Yuanwei Zhang, Xiling Yue, Sheng Yao, Mykhailo V. Bondar and Kevin D. Belfield

Molecules 2016, 21(6), 709; https://doi.org/10.3390/molecules21060709 - 30 May 2016

Cited by 6 | Viewed by 5997

Abstract

A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce [...] Read more.

A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce potential phototoxicity that is characteristic of using UV light to excite common fluorphores, better discriminate from native autofluorescence, and potentially facilitate deep tissue imaging. An impressive 30-fold enhancement of fluorescence intensity of dU-BZ was achieved upon increasing viscosity. Fluorescence quantum yields in 99% glycerol/1% methanol (v/v) solution as a function of temperature (293–343 K), together with viscosity-dependent fluorescence lifetimes and radiative and non-radiative rate constants in glycerol/methanol solutions (ranging from 4.8 to 950 cP) were determined. Both fluorescence quantum yields and lifetimes increased with increased viscosity, consistent with results predicted by theory. This suggests that the newly-designed compound, dU-BZ, is capable of functioning as a probe of local microviscosity, an aspect examined by in vitro bioimaging experiments. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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Review

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3625 KiB

Open AccessReview

Recent Advances in Macrocyclic Fluorescent Probes for Ion Sensing

by Joseph K.-H. Wong, Matthew H. Todd and Peter J. Rutledge

Molecules 2017, 22(2), 200; https://doi.org/10.3390/molecules22020200 - 25 Jan 2017

Cited by 59 | Viewed by 9059

Abstract

Small-molecule fluorescent probes play a myriad of important roles in chemical sensing. Many such systems incorporating a receptor component designed to recognise and bind a specific analyte, and a reporter or transducer component which signals the binding event with a change in fluorescence [...] Read more.

Small-molecule fluorescent probes play a myriad of important roles in chemical sensing. Many such systems incorporating a receptor component designed to recognise and bind a specific analyte, and a reporter or transducer component which signals the binding event with a change in fluorescence output have been developed. Fluorescent probes use a variety of mechanisms to transmit the binding event to the reporter unit, including photoinduced electron transfer (PET), charge transfer (CT), Förster resonance energy transfer (FRET), excimer formation, and aggregation induced emission (AIE) or aggregation caused quenching (ACQ). These systems respond to a wide array of potential analytes including protons, metal cations, anions, carbohydrates, and other biomolecules. This review surveys important new fluorescence-based probes for these and other analytes that have been reported over the past five years, focusing on the most widely exploited macrocyclic recognition components, those based on cyclam, calixarenes, cyclodextrins and crown ethers; other macrocyclic and non-macrocyclic receptors are also discussed. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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2394 KiB

Open AccessReview

Small Molecule-Photoactive Yellow Protein Labeling Technology in Live Cell Imaging

by Feng Gao, Tang Gao, Kechao Zhou and Wenbin Zeng

Molecules 2016, 21(9), 1163; https://doi.org/10.3390/molecules21091163 - 31 Aug 2016

Cited by 7 | Viewed by 8278

Abstract

Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro [...] Read more.

Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro and in live cells or in vivo. A peptide or a protein tag fused to the protein of interest and provides the opportunities for an attachment of small molecule probes or other fluorophore to image the dynamics of protein localization. Here we reviewed the recent development of no-wash small molecular probes for photoactive yellow protein (PYP-tag), by the means of utilizing a quenching mechanism based on the intramolecular interactions, or an environmental-sensitive fluorophore. Several fluorogenic probes have been developed, with fast labeling kinetics and cell permeability. This technology allows quick live-cell imaging of cell-surface and intracellular proteins without a wash-out procedure. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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4347 KiB

Open AccessReview

Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

by Susann Schröder, Barbara Wenzel, Winnie Deuther-Conrad, Matthias Scheunemann and Peter Brust

Molecules 2016, 21(5), 650; https://doi.org/10.3390/molecules21050650 - 19 May 2016

Cited by 20 | Viewed by 6781

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition [...] Read more.

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET) in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-)clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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3869 KiB

Open AccessReview

MRI Reporter Genes for Noninvasive Molecular Imaging

by Caixia Yang, Rui Tian, Ting Liu and Gang Liu

Molecules 2016, 21(5), 580; https://doi.org/10.3390/molecules21050580 - 18 May 2016

Cited by 36 | Viewed by 9330

Abstract

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific [...] Read more.

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase), the receptor on the cells (e.g., transferrin receptor), and endogenous reporter genes (e.g., ferritin reporter gene). However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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