Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

Design of Novel 18F-Labeled Amino Acid Tracers Using Sulfur 18F-Fluoride Exchange Click Chemistry.

[18F]Gln-OSO2F, [18F]Arg-OSO2F, and [18F]FSY-OSO2F were designed by introducing sulfonyl 18F-fluoride onto glutamine, arginine, and tyrosine, respectively. [18F]FSY-OSO2F can be prepared directly by sulfur 18F-fluoride exchange, while [18F]Gln-OSO2F and [18F]Arg-OSO2F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [18F]FSY-OSO2F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [18F]FET. However, [18F]Gln-OSO2F and [18F]Arg-OSO2F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages.

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging.

Fibroblast activation protein (FAP) is closely related to central nervous system diseases such as stroke and brain tumors, but PET tracers that can be used for brain imaging have not been reported. Here, we designed, synthesized, and evaluated 18F-labeled UAMC1110 derivatives suitable for brain imaging targeting FAP. By substituting the F atom for the H atom on the aromatic ring of compound UAMC1110, 1a-c were designed and prepared. 1a-c were confirmed to have a high affinity for FAP through molecular docking and enzyme assay. [18F]1a-c were successfully prepared and confirmed to have high affinity. The stability in vivo indicates that no obvious metabolites of [18F]1a,b were found in the plasma 1 h after injection, which is beneficial for brain imaging. In vitro cell uptake experiments showed that [18F]1a,b and [68Ga]FAPI04 exhibited similar uptake and internalization rates. PET imaging of U87MG subcutaneous tumor showed that [18F]1a,b could penetrate the blood-brain barrier with higher uptake and longer retention time than [68Ga]FAPI04 (uptake at 62.5 min, 1.06 ± 0.23, 1.09 ± 0.25% ID/g vs 0.21 ± 0.10% ID/g, respectively). The brain-to-blood ratios of [18F]1a,b were better than [68Ga]FAPI04. Biodistribution and PET imaging showed that [18F]1a had better uptake on tumors and a higher tumor-to-muscle ratio than [18F]1b and [68Ga]FAPI04. Further imaging of U87MG intracranial glioma showed that [18F]1a outlined high-contrast gliomas in a short period of time compared to [18F]1b. Therefore, [18F]1a is expected to be useful in the diagnosis of FAP-related brain diseases.

Design, Synthesis, and Biological Evaluation of a Novel [18F]-Labeled Arginine Derivative for Tumor Imaging.

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro-18F)ethoxy)benzyl)-5-guanidinopentanoic acid ([18F]7) was designed and prepared by introducing [18F]fluoroethoxy benzyl on carbon-4 of arginine. [18F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[18F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [18F]7 was similar to (2S,4S)4-[18F]FPArg and was transported into tumor cells by cationic amino acid transporters. However, [18F]7 can also enter MCF-7 cells via ASC and ASC2 amino acid transporters. Further microPET-CT imaging showed that the initial uptake and retention properties of [18F]7 in MCF-7 subcutaneous tumors were good (2.29 ± 0.09%ID/g at 2.5 min and 1.71 ± 0.09%ID/g at 60 min after administration), without significant defluorination in vivo. However, compared to (2S,4S)4-[18F]FPArg (3.06 ± 0.59%ID/g at 60 min after administration), [18F]7 exhibited lower tumor uptake and higher nonspecific uptake. When further applied to U87MG imaging, [18F]7 can quickly visualize brain gliomas (tumor-to-brain, 1.85 at 60 min after administration). Therefore, based on the above results, [18F]7 will likely be applied for the diagnosis of arginine nutrition-deficient tumors and efficacy evaluations.

Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging.

Glutamine metabolism-related tracers have the potential to visualize numerous tumors because glutamine is the second largest source of energy for tumors. (2S,4S)-4-[18F]FEBGln was designed by introducing [18F]fluoroethoxy benzyl on carbon-4 of glutamine. The aim of this study was to investigate the pharmacokinetic properties and tumor positron emission tomography (PET) imaging characteristics of (2S,4S)-4-[18F]FEBGln in detail. The biodistribution results of nude mice bearing MCF-7 tumor showed that (2S,4S)-4-[18F]FEBGln had high initial tumor uptake, and a fast clearance rate, resulting in a high tumor-to-muscle ratio at 30 min postinjection. There was no obvious defluorination in vivo. The micro-PET-CT imaging results of (2S,4S)-4-[18F]FEBGln orthotopic MCF-7 tumor-bearing nude mice were consistent with the biological distribution results. Compared with (2S,4R)-4-[18F]FGln, (2S,4S)-4-[18F]FEBGln showed poor tumor retention, but its clearance in normal tissues was also fast, so it had better PET image contrast than the former. Unlike poor retention in MCF-7-bearing nude mice, (2S,4S)-4-[18F]FEBGln has good retention in NCI-h1975 and 22Rv1 tumor models. Since (2S,4S)-4-[18F]FEBGln has low uptake in normal lungs and high uptake in the bladder, it is expected to be used in the accurate diagnosis of lung cancer but cannot accurately determine prostate cancer. Consistent with the advantages of radiolabeled amino acids in the application of brain tumors, (2S,4S)-4-[18F]FEBGln accurately diagnoses U87MG glioma with higher contrast than [18F]FET and [18F]FDG, and there is a correlation between (2S,4S)-4-[18F]FEBGln uptake and tumor growth cycle. Further kinetic model analysis showed that (2S,4S)-4-[18F]FEBGln was similar to (2S,4R)-4-[18F]FGln, conforming to the one-compartment model and the Logan graphical model, and was expected to assess the size of the glutamine pool of the tumor. Therefore, (2S,4S)-4-[18F]FEBGln is expected to provide a strong imaging basis for the diagnosis, formulation of personalized plans, and efficacy evaluation of glioma, lung cancer, and breast cancer.

Direct Observation of Photon Induced Giant Band Renormalization in 2D PdSe2 Dichalcogenide by Transient Absorption Spectroscopy.

Insight into fundamental light-matter interaction as well as underlying photo-physical processes is crucial for the development of novel optoelectronic devices. Palladium diselenide (PdSe2 ), an important representative of emerging 2D noble metal dichalcogenides, has gain considerable attention owing to its unique optical, physical, and chemical properties. In this study, 2D PdSe2 nanosheets (NSs) are prepared using the liquid-phase exfoliation method. A broadband carrier relaxation dynamics from visible to near-infrared bands are revealed using a time-resolved transient absorption spectrometer, giving results that indicate band filling and bandgap renormalization (BGR) effects in the 2D PdSe2 NSs. The observed blue-shift of the transient absorption spectra at the primary stage and the subsequent red-shift can be ascribed to this BGR effect. These findings reveal the many-body character of the 2D TMDs material and may hold keys for applications in the field of optoelectronics and ultrafast photonics.

Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aß Plaques.

Accurate quantification of amyloid beta (Aß) plaques is an important indicator for Alzheimer's disease diagnosis and treatment. For this purpose, new highly sensitive Aß tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]BIBD-124 and [18F]BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]BIBD-124/127 were similar to that of [18F]AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]BIBD-124 could monitor Aß plaques similar to [18F]AV45. Besides, the imaging contrast of [18F]BIBD-124 is better than that of [18F]AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]BIBD-124 is expected to be a promising radiotracer of Aß plaques for further clinical trials.

Shakedown Analysis and Experimental Study of Thermal Barrier Coatings.

Interfacial stress-strain fields become complicated in thermal barrier coatings (TBCs) under cyclic thermal loading, which affects the stability and spalling failure of TBCs directly. The convex and concave interfacial structures of TBCs were approximated as a multilayer cylinder model, and an analytical method of TBCs for shakedown analysis was established. A series of 8-YSZ TBC specimens were prepared by the plasma spraying process, followed by isothermal and thermal shock tests. The results showed that the stability limit is significantly greater than the elastic limit, the limit for the convex model was higher than that in the concave model, the first failure occurs in the concave area, and the main failure mode of a thermal barrier coating is the appearance of cracks at the interface layer during a thermal shock test. For the coating samples prepared in this study, the stability limits were between 950 °C and 1050 °C, and the validity of the stability limit analysis model of a multilayer structure was verified.

Optimization of Precursor Synthesis Conditions of (2S,4S)4-[18F]FPArg and Its Application in Glioma Imaging.

Although the tracer (2S,4S)4-[18F]FPArg is expected to provide a powerful imaging method for the diagnosis and treatment of clinical tumors, it has not been realized due to the low yield of chemical synthesis and radiolabeling. A simple synthetic method for the radiolabeled precursor of (2S,4S)4-[18F]FPArg in stable yield was obtained by adjusting the sequence of the synthetic steps. Furthermore, the biodistribution experiments confirmed that (2S,4S)4-[18F]FPArg could be cleared out quickly in wild type mouse. Cell uptake experiments and U87MG tumor mouse microPET-CT imaging experiments showed that the tumor had high uptake of (2S,4S)4-[18F]FPArg and the clearance was slow, but (2S,4S)4-[18F]FPArg was rapidly cleared in normal brain tissue. MicroPET-CT imaging of nude mice bearing orthotopic HS683-Luc showed that (2S,4S)4-[18F]FPArg can penetrate blood-brain barrier and image gliomas with a high contrast. Therefore, (2S,4S)4-[18F]FPArg is expected to be further applied in the diagnosis and efficacy evaluation of clinical glioma.

[18F]BIBD-239: 18F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein.

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of 11C (20.38 min). To overcome the deficiency of [11C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [18F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [18F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [18F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [18F]BIBD-239 did not interfere with brain imaging. Conclusively, [18F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

Novel 18F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation.

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of 18F-labeled and 68Ga-labeled potential aromatase-binding candidate compounds were designed and synthesized based on the structures of aromatase inhibitors. Competitive inhibition experiments in vitro and molecular docking showed that BIBD-069 and BIBD-071 have high affinity for aromatase. The radiolabeling conditions of [18F]BIBD-069 and [18F]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [18F]BIBD-069 and [18F]BIBD-071 specifically bind to aromatase. [18F]BIBD-069 and [18F]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [11C]vorozole. Radiometabolites of [18F]BIBD-069 and [18F]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [18F]BIBD-069 and [18F]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [18F]BIBD-069 and [18F]BIBD-071 exhibit excellent aromatase binding affinities, mild radiolabeling conditions, and good pharmacokinetics, they can be important tools for the diagnosis and treatment of aromatase-related diseases.

[18F]BIBD-181: A Novel Positron Emission Tomography Tracer Specific for Synaptic Vesicle Glycoprotein 2A.

Dysfunction or decreased expression of synaptic vesicle glycoprotein 2A (SV2A) is closely related to the progression of neurodegenerative diseases and psychiatric disorders. The development of positron emission tomography (PET) tracers targeting SV2A can provide a strong imaging basis for the diagnosis and treatment of these diseases. Herein we report the synthesis of the novel radiotracer [18F]BIBD-181 and its preclinical evaluation. The absolute configuration of BIBD-181 was confirmed by the single-crystal structure of its precursor. The in vitro binding assay of BIBD-181 showed high SV2A binding affinity. Compared with previously reported tracers, [18F]BIBD-181 has mild labeling conditions, simple operation, and high yield. The in vivo metabolism of [18F]BIBD-181 is similar to that of UCB derivatives, and the metabolites do not interfere with brain PET imaging. Biodistribution and PET studies showed that [18F]BIBD-181 has high brain uptake and good pharmacokinetics. Autoradiography and PET inhibition studies indicated that [18F]BIBD-181 specifically binds SV2A. Because [18F]BIBD-181 exhibits excellent properties, it may be a reliable probe of quantities for SV2A-related disease diagnosis.

Optical Properties of Few-Layer Ti3CN MXene: From Experimental Observations to Theoretical Calculations.

Despite the emerging interest in research and development of Ti3CN MXene nanosheet (NS)-based optoelectronic devices, there is still a lack of in-depth studies of the underlying photophysical processes, like carrier relaxation dynamics and nonlinear photon absorption, operating in such devices, hindering their further and precise design. In this paper, we attempt to remedy the situation by fabricating few-layer Ti3CN NSs via combining selective etching and molecular intercalation and by investigating the carrier relaxation possesses and broadband nonlinear optical responses via transient absorption and Z-scan techniques. These results are complemented by first-principle theoretical analyses of the optical properties. Both saturable absorption and reverse saturable absorption phenomena are observed due to multiphoton absorption effects. The analysis of these results adds to the understanding of the basic photophysical processes, which is anticipated to be beneficial for the further design of MXene-based devices.

Tailoring the ultrafast and nonlinear photonics of MXenes through elemental replacement.

Due to the outstanding electronic properties, unique chemical surface termination units and rich elemental compositions, MXenes have become promising candidates for the development of new generation optoelectronic devices. However, there is still a gap between advanced photonics applications and fundamental understanding of ultrafast carrier photo-physics dynamics and a nonlinear optical response in layered MXenes. Here, we present insight into the excited state relaxation processes and nonlinear optical response of few-layer Ti3CN and Ti3C2 nanosheets (NSs) via transient absorption spectroscopy and Z-scan measurements. Owing to similar structural compositions, the transient absorption and nonlinear absorption characteristics behave totally opposite. In addition, photo-induced bandgap renormalization and Pauli blocking phenomena exist in Ti3C2 and Ti3CN NSs, respectively. The element replacement may be a new strategy for tunable carrier kinetics and nonlinear optical response of MXenes. These research studies may provide insight into ultrafast carrier photo-physics dynamics as well as promote MXene-based advanced photonics and their applications in optoelectronic devices.

Defect Engineering in Ultrathin SnSe Nanosheets for High-Performance Optoelectronic Applications.

Ultrathin lamellar SnSe is highly attractive for applications in areas such as photonics, photodetectors, photovoltaic devices, and photocatalysis, owing to its suitable band gap, exceptional light absorption capabilities, and considerable carrier mobility. On the other hand, SnSe nanosheets (NSs) still face challenges of being difficult to prepare and their devices having low photoelectric conversion efficiencies. Herein, ultrathin SnSe NSs with controlled Se defects were synthesized with high yield by a facial Li intercalation-assisted liquid exfoliation method. The loss of Se, a narrowing of the band gap, and an increase in lattice disorders involving vacancies, distortions, and phase transition were observed in SnSe NSs prepared with a long lithiation process. Comparing between the 24 and 72 h lithiation samples, the ones processed for a longer time displayed a faster recombination time due to more defect-induced mid-states. Inspiringly, enhancements of 4-10 times were observed for photodetector device parameters such as photocurrent, photoresponsivity, photoresponse speed, and specific detectivity of the 72 h lithiation SnSe NSs. Additionally, these devices show good stability and a broad detection range, from ultraviolet to the near infrared region. Our results provide a promising avenue for the mass production of SnSe NSs with high photoelectric performance and open up opportunities for applications in photonics, optoelectronics, and photocatalysis.

Apoptosis inducing properties of 3-biotinylate-6-benzimidazole B-nor-cholesterol analogues.

In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferativeactivities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.

Self-Assembly of Size-Controlled m-Pyridine-Urea Oligomers and Their Biomimetic Chloride Ion Channels.

The m-pyridine urea (mPU) oligomer was constructed by using the intramolecular hydrogen bond formed by the pyridine nitrogen atom and the NH of urea and the intermolecular hydrogen bond of the terminal carbonyl group and the NH of urea. Due to the synergistic effect of hydrogen bonds, mPU oligomer folds and exhibits strong self-assembly behaviour. Affected by folding, mPU oligomer generates a twisted plane, and one of its important features is that the carbonyl group of the urea group orientates outwards from the twisted plane, while the NHs tend to direct inward. This feature is beneficial to NH attraction for electron-rich species. Among them, the trimer self-assembles into helical nanotubes, and can efficiently transport chloride ions. This study provides a novel and efficient strategy for constructing self-assembled biomimetic materials for electron-rich species transmission.

Studies on apoptosis induced by B-norcholesteryl benzimidazole compounds in HeLa cells.

Certain B-norcholesteryl benzimidazole compounds were found to mediate marked anti-tumor proliferative effects in vitro in our earlier study. Here, the mechanism of action of these anti-tumor effects was evaluated using HeLa human cervical cancer cells. Methods for detecting cell invasion and migration, Annexin V-PI double staining, cell cycle status, and mitochondrial membrane potential Δψm were employed. These compounds were confirmed to significantly inhibit the proliferation of HeLa cells in vitro. Compound 1 induced apoptosis in S phase, compound 2induced apoptosis in the G0/G1 phase and compound 3 induced late apoptosis in the G2/M phase. These compounds induced HeLa cell apoptosis through depolarization of mitochondrial membrane potential Δψm in a dose-dependent manner. B-norcholesteryl benzimidazole compounds induced morphological changes in HeLa cells and inhibited proliferation, invasion and metastasis. Apoptosis was promoted by mechanisms involving p21 and p53 in this cervical cancer cell line.

Synthesis and preliminary evaluation of a PET-FI bimodal imaging agent targeting estrogen receptor.

Estrogen receptor is an attractive target for the diagnosis and treatment of breast cancer. This article reports for the first time a dual-modality imaging agent targeting estrogen receptor that can use PET imaging to diagnose breast cancer and utilize fluorescence imaging to achieve intraoperative navigation. Fluorescence experiments show that [natGa] 1 has typical aggregate induced emission characteristics. Above the critical concentration, [natGa] 1 can form biocompatible nanomicelles. [natGa] 1 can quickly light up estrogen receptor positive MCF-7 cells. Cell uptake experiments show that [68Ga] 1 is mediated by estrogen receptor. Therefore, [nat/68Ga] 1 shows the characteristics of highly sensitive diagnosis and visualization of breast cancer, and can be used as a lead compound for the development of a novel PET-FI bimodal imaging agent targeting the estrogen receptor.