Dual-modality Probe Research Articles

PET-Based Dual-Modal Probes for In Vivo Imaging.

Molecular imaging has significantly advanced the detection and analysis of in vivo metabolic processes, while single-modal techniques remain limited. Dual-modal imaging, particularly positron emission tomography (PET)-based combinations has emerged as a powerful solution, offering enhanced capabilities through integration with magnetic resonance imaging (MRI) or near-infrared fluorescence (NIRF) imaging. This review highlights recent progress in PET-based dual-modal imaging, focusing on the development of various bimodal probes derived from antibodies, nanoparticles, and peptides, and key applications including image-guided surgery and disease assessment. PET-based dual-modal imaging holds substantial potential for advancing research and diagnostics by improving resolution and providing functional insights. By combining complementary modalities, these systems deliver a more comprehensive view of disease processes, leading to more accurate diagnoses and targeted treatments. Future research prioritizes optimizing probe design for enhanced biocompatibility and safety, facilitating clinical translation, and broadens applications beyond cancer. Through interdisciplinary collaboration, PET-based dual-modal probes are poised to play a pivotal role in improving patient outcomes, particularly in diagnosing and managing complex diseases.

A dual-mode fluorescent probe for temperature-sensing and metal ions detection based on castor leaves-derived carbon quantum dots

A dual-mode fluorescent probe for temperature-sensing and metal ions detection based on castor leaves-derived carbon quantum dots

Novel Dual-Functional Half-Curcumin Analogues as a Fluorescent and PET Probe for β-Amyloid Imaging in the Alzheimer's Disease APP/PS1 Model.

Noninvasive imaging of β-amyloid in vivo is pivotal for the early diagnosis of Alzheimer's disease (AD). While single imaging methods have been extensively studied for detecting Aβ over the past decade, dual-modal probes have received scant attention. In this study, we synthesized and assessed a series of half-curcumin probes, among which DiFboron-8 demonstrated a high affinity and selectivity for Aβ aggregates. DiFboron-8 effectively served as a dual-functional fluorescent and positron emission tomography (PET) probe for imaging β-amyloid in an AD mouse model. Histological staining results underscored DiFboron-8's potent staining capability for Aβ plaques in APP/PS1 brain slices, while ex vivo biodistribution studies highlighted its rapid clearance rate. In vivo imaging revealed that [18F]-DiFboron-8 could penetrate the blood-brain barrier, displaying higher PET signals in the brains of APP/PS1 mice compared to wild-type mice just 3 min postinjection, a finding corroborated by autoradiography staining. Overall, we propose that [18F]-DiFboron-8 represents an efficient fluorescent/PET dual-modal probe, offering promise for β-amyloid imaging in the early stages of AD.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper. NIRF-PA-HClO showed excellent NIRF/PA dual-modal responses with high SBRs for HClO in solution, cells, and mice. Moreover, NIRF-PA-HClO was successfully applied for high-contrast imaging of DILI. Finally, NIRF-PA-HClO was employed for the blood plasma diagnosis of sepsis with satisfactory results. In summary, the above results proved that NIRF-PA-HClO would be a potentially useful tool for the study of physiological and pathological roles of HClO, the investigation of the pathology and therapeutic mechanisms of hepatotoxicity, and the diagnosis of blood infection. Also, the development of NIRF-PA-HClO provides new design mentality for constructing other analyte-activatable NIRF/PA dual-modal probes with high SBRs.

Development of a colorimetric/fluorescence dual-mode immunoassay for aflatoxin B1 based on streptavidin-induced gold nanoparticle aggregation.

Adual-mode immunoassay method was developed for colorimetric and fluorescence detection of aflatoxin B1 (AFB1) based on streptavidin-induced gold nanoparticle aggregation (AuNP@SA). AuNP-modified streptavidin-biotin labeling AFB1 complete antigen aggregations (AuNP@SA@Bio-BSA-AFB1) were synthesized as the competitive binding and dual-mode probe. AuNP@SA@Bio-BSA-AFB1 aggregations possessed high colorimetric and fluorescence quenching intensities. AFB1 antibodies modified immunomagnetic microspheres were used as the capture probe. The competitive binding between AFB1 and AuNP@SA@Bio-BSA-AFB1 leads to changes in color and fluorescence intensity. The detection limit of the colorimetric method is 6.95ng·mL-1, while that ofthe fluorescence method is 0.07ng·mL-1. The practicality of the proposed strategy was demonstrated bydetermining AFB1 in spiked peanut samples.

Application of rare earth elements in dual-modality molecular probes.

The unique 4f subshell electronic structure of rare earth elements endows them with exceptional properties in electrical, magnetic, and optical domains. These properties include prolonged fluorescence lifetimes, large Stokes shifts, distinctive spectral bands, and strong resistance to photobleaching, making them ideal for the synthesis of molecular probes. Each imaging technique possesses unique advantages and specific applicabilities but also inherent limitations due to its operational principles. Dual-modality molecular probes effectively address these limitations, particularly in applications involving high-resolution Magnetic Resonance Imaging (MRI) such as MRI/OI, MRI/PET, MRI/CT, and MRI/US. This review summarizes the applications, advantages, challenges, and current research status of rare earth elements in these four dual imaging modalities, providing a theoretical basis for the future development and application of rare earth elements in the field of dual-modality molecular probes.

A mitochondria-targeted NIR fluorescence/photoacoustic dual-modality probe for highly sensitive and selective imaging of HClO in vivo

A mitochondria-targeted NIR fluorescence/photoacoustic dual-modality probe for highly sensitive and selective imaging of HClO in vivo

Comparison of Two Chelator Scaffolds as Basis for Cholecystokinin-2 Receptor Targeting Bimodal Imaging Probes.

Background/Objectives: Dual-modality probes, combining positron emission tomography (PET) with fluorescence imaging (FI) capabilities in a single molecule, are of high relevance for the accurate staging and guided resection of tumours. We herein present a pair of candidates targeting the cholecystokinin-2 receptor (CCK2R), namely [68Ga]Ga-CyTMG and [68Ga]Ga-CyFMG. In these probes, the SulfoCy5.5 fluorophore and two units of a CCK2R-binding motif are coupled to the chelator acting as a core scaffold, triazacyclononane-phosphinic acid (TRAP), and Fusarinine C (FSC), respectively. Using this approach, we investigated the influence of these chelators on the final properties. Methods: The synthetic strategy to both precursors was based on the stoichiometric conjugation of the components via click chemistry. The characterization in vitro included the evaluation of the CCK2R affinity and internalization in A431-CCK2R cells. Ex vivo biodistribution as well as PET and FI studies were performed in xenografted mice. Results: 68Ga labelling was accomplished with high radiochemical yield and purity for both precursors. A CCK2R affinity in the subnanomolar range of the conjugates and a receptor-specific uptake of the radioligands in cells were observed. In A431-CCK2R/A431-mock xenografted mice, the investigated compounds showed specific accumulation in the tumours and reduced off-target uptake compared to a previously developed compound. Higher accumulation and prolonged retention in the kidneys were observed for [68Ga]Ga-CyTMG when compared to [68Ga]Ga-CyFMG. Conclusions: Despite the promising targeting properties observed, further probe optimization is required to achieve enhanced imaging contrast at early timepoints. Additionally, the results indicate a distinct influence of the chelators in terms of renal accumulation and retention.

Construction of a Dual-Mode Sensing Platform for Ultra-fast Detection of Bisulfite in Food and Environmental Systems.

Sulfur dioxide (SO2) is widely used in food processing to extend the shelf life of food. However, excessive intake of SO2 and its derivatives (HSO3- and SO32-) can cause oxidative damage to the body, and result in several diseases. How to construct probes for rapid real-time detection of HSO3- in the field is beneficial to the developmental needs of practical applications, but it is also very challenging. Here we report a dual-mode fluorescent probe Rh-QL for ultrafast detection of HSO3-, which undergoes a specific 1,4-Michael addition reaction with HSO3- to achieve near-infrared fluorescence turn-on. Probe Rh-QL can rapidly (< 5s) respond to HSO3- with a color change from purple to green and a strong fluorescence emission at 725nm. The probe Rh-QL has been used for the detection of HSO3- in real sugar samples and can be prepared as a portable sensing kit for the detection of HSO3- in the environment due to its high efficiency, rapidity and accuracy. In addition, the probe Rh-QL is able to target label Gram-negative bacteria after reacting with HSO3-, which has the potential to identify the type of pathogenic bacteria.

Dual-mode fluorescent probe for rapid lead detection in water and gasoline based on a perylene/β-cyclodextrin hybrid sensor

Lead is a toxic heavy metal utilized in various industrial applications, presenting considerable environmental and health hazards. Thus, its rapid detection is necessary in various industrial applications to prevent its toxic effecs. This study introduces a novel fluorescent probe utilizing perylene-3,4,9,10-tetracarboxylic diimide (PTCDI) modified with β-cyclodextrin (B_CD) to lead ion detection and mitigate the inherent hydrophobicity of PTCDI. B_CD is initially modified with aldehyde groups (B_CDA) and subsequently linked to PTCDI through the Schiff-base reaction to produce the final PI_CDA probe. The synthesis of PI_CDA is confirmed through Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies. Field emission scanning electron microscopy (FE-SEM) demonstrates distinct self-assembly structures, transitioning from clumped aggregates in B_CD to elongated cylindrical morphologies in PI_CDA, thereby underscoring the influence of chemical modification on nanostructure formation. The probe demonstrates enhanced fluorescence emission through the photoinduced electron transfer (PET) mechanism, facilitating the selective detection of lead ions while avoiding interference from other metal cations. The detection limit of this sensor for lead ions is determined 1.6 μM, with a maximum detection range of 55 μM. Furthermore, PI_CDA exhibits effective lead detection in gasoline, addressing a notable environmental issue.

Dual-mode visual imaging of latent fingerprints based on organic fluorescent probe with enhanced TICT emission

Fluorescence-based imaging has emerged as a promising technique for high-resolution visualization of latent fingerprints (LFPs), but detecting LFPs by fluorescent probes remains challenging at present. Herein, a water-soluble fluorescent dye (DEPN) with red emission and twisted intramolecular charge transfer (TICT) properties was synthesized, which function as a dual-mode in-situ imaging probe for LFPs. The desired solid composite fluorescent fingerprint powder DEPN@MMT can be obtained by milling with montmorillonite (MMT) to realize the imaging of LFPs with 1–3 levels of details, which has the advantages of simple preparation, low doping ratio, good photostability, and is not limited by the substrate. Comparison with the actual fingerprint details extracted by fingerprint reader revealed a good match between the both, indicating that the fingerprint powder has high application value. The permanent preservation of LFPs with different curvatures was also realized by making rubbings. In addition, DEPN was able to image LFPs in aqueous solution with a concentration of 50 μM over a wide pH range, and it took only 20 s to obtain high-quality images that met the NFIQ2 detection standard. This dual-mode imaging probe of LFPs is highly practical, offering adaptable detection patterns for a range of complicated situations. It provides a valuable method for rapid and convenient visualization of LFPs, as well as their subsequent preservation and analysis.

Controllable fabrication of high-quantum-yield bimetallic gold/silver nanoclusters as multivariate sensing probe for Hg2+, H2O2, and glutathione based on AIE and peroxidase mimicking activity

The grave threat posed by heavy metals and food hazards has increased the urgency of rapid and precise detection for food security and human health. Efficient multivariate sensing probes are imperatively required for sensing heavy metals and tumor markers, which are still facing great challenge in terms of multi-functional integration. Here, bimetallic gold-silver nanoclusters (NG-AuAgNCs) were developed with unique aggregation-induced-emission (AIE) property and peroxidase (POD) mimicking activity towards the efficient multivariate sensing via optimization of the precursors. The NG-AuAgNCs emitted at 614 nm and enable AIE feature with lifetime of 12.61 μs and high quantum yield of 40.5%. Possessing AIE and POD activity, the NG-AuAgNCs show great potential as fluorimetric and colorimetric dual-mode probe for multivariate sensing Hg2+, H2O2 and GSH, with good recoveries in real samples. The NG-AuAgNCs paper sensors further integrating with smartphone, achieved portable detection of Hg2+ with limit of detection (LOD) of 19 nM, while the colorimetric-mode presented consecutive response to H2O2 and GSH via a reversible oxidase tetramethylbenzidine process with LODs of 7.02 and 0.45 μM, respectively. This work not only demonstrates a multivariate probe for environment and human health, but also provides valuable insights for the function integration of the nanocluster via synthetic manipulation.

Bimetallic metal organic frameworks-based nanozyme for colorimetry/fluorescence dual-mode uremic toxin detection

Chronic kidney disease (CKD) can greatly increase the mortality risk for clinical patients, with a major challenge being the accurate detection of uremic toxins. Metal organic frameworks (MOFs)-based colorimetry/fluorescence dual-mode probe have shown great potential for bio-detection. However, one of the challenges for MOFs-based nanoprobe is to effectively improve the activity of mimetic enzymes for colorimetric assays while maintaining their outstanding luminescence response for fluorescence sensing. Here, we developed a novel bimetallic Zr/Ce-MOFs, which possesses high catalytic activity and excellent luminescence properties for dual-mode sensing of uremic toxins. The co-existence of Ce and Zr in the MOFs improves the catalytic activity for colorimetric detection of phosphate ions (one type of uremic toxins) and the strong coordinate covalent interaction between phosphate ions and Zr/Ce leads to a significant fluorescence enhancement of the MOFs. Furthermore, we achieved high sensitivity phosphate ions analysis in serum samples. This strategy provides an easy and reliable platform for the detection of uremic toxins in complicated physiological environment.

Fluoropolymer-Gadolinium(III) Hybrids for Photoactivatable Dual-Mode T1-Weighted 1H MRI and 19F MRI Contrast Agents.

Multimodal imaging probes play a crucial role in overcoming the limitations associated with single-mode imaging for clinical medical diagnosis. This study focuses on the development of a photoresponsive fluorine-containing water-soluble polymer (PF) through RAFT polymerization. Subsequently, a polymer-gadolinium(III) hybrid (PF-Gd) dual-modal probe capable of T1-weighted 1H MRI and 19F MRI was synthesized via postmodification of PF with a Gd-DOTA derivative. Under physiological conditions (pH = 7.4), the hybrids exhibit UV-activated 19F NMR/MRI and enhanced 1H MRI. The inclusion of Gd3+ facilitates the acceleration of water molecule T1 relaxation, leading to high-intensity 1H MRI contrast. Leveraging the paramagnetic relaxation enhancement (PRE) effect between fluorine atoms and Gd3+, the restoration of Gd3+-accelerated 19F T2 relaxation enables precise photoactivation of 19F MRI signals, transitioning from the "OFF" to the "ON" state. This study provides an important reference for the development of hybrid systems that function as real-time diagnostic tools and offers controlled activation for multimodal imaging probes.

In vivo targeted-imaging of mitochondrial acidification in an aristolochic acid I-induced nephrotoxicity mouse model by a fluorescent/photoacoustic bimodal probe

Aristolochic acid I (AAI), a natural compound in aristolochia type Chinese medicinal herb, is generally acknowledged to have nephrotoxicity, which may be associated with mitophagy. Mitophagy is a cellular process with important functions that drive AAI-induced renal injury. Mitochondrial pH is currently measured by fluorescent probes in cell culture, but existing probes do not allow for in situ imaging of AAI-induced mitophagy in vivo. We developed a ratiometric fluorescent/PA dual-modal probe with a silicon rhodamine fluorophore and a pH-sensitive hemicyanine dye covalently linked via a short chain to obtain a FRET type probe. The probe was used to measure AAI-mediated mitochondrial acidification in live cells and in vivo. The Förster resonance energy transfer (FRET)-mediated ratiometric and bimodal method can efficiently eliminate signal variability associated with the commonly used one-emission and single detection mode by ratiometric two channels of the donor and acceptor. The probe has good water-solubility and low molecular weight with two positively charged, facilitating its precise targeting into renal mitochondria, where the fluorescent/PA changes in response to mitochondrial acidification, enabling dynamic and semi-quantitative mapping of subtle changes in mitochondrial pH in AAI-induced nephrotoxicity mouse model for the first time. Also, the joint use of L-carnitine could mitigate the mitophagy in AAI-induced nephrotoxicity.

Fluorescence and Circular Dichroism Dual-Mode Probe for Chiral Recognition of Tyrosine and Its Applications in Bioimaging.

Chiral amino acids (AAs) are essential in metabolism and understanding physiological processes, and they could be used as biomarkers for the diagnosis of different diseases. In this study, chiral Cdots@Van were prepared by postmodifying an achiral Cdots core with vancomycin for recognizing and determining the enantiomeric excess (ee) of tyrosine (Tyr) enantiomers. The fluorescence response of Cdots@Van is based on an "on-off" strategy, with different quenching percentages for d- and l-tyrosine. Interestingly, the circular dichroism (CD) spectrum of Cdots@Van responded to only one form of Tyr enantiomer, specifically d-Tyr, and remained nearly unchanged upon the addition of l-Tyr. Quantum mechanical (QM) calculations were in excellent agreement with the experimental results, confirming the stronger binding affinity of Cdots@Van for d-Tyr compared to l-Tyr. We further investigated the chiral recognition ability of the interconnected vancomycin particles, which was synthesized using the EDC/NHS coupling reaction between vancomycin molecules without a Cdots core. Surprisingly, unlike free vancomycin molecules, interconnected vancomycin displayed an enantiomeric recognition ability by CD spectroscopy, similar to what was observed for Cdots@Van. Crucially, this chiral probe has been successfully utilized for cell imaging applications.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C–C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

A turn-on anthraquinone-derived colorimetric and fluorometric dual-mode probe for highly selective Hg2+ determination and bioimaging in living organisms

Mercury ion (Hg2+) is considered a harmful neurotoxin, and real-time monitoring of Hg2+ concentrations in environmental and biological samples is critical. Fluorescent probes are a rapidly emerging visualization tool owing to their simple design and good selectivity. Herein, a novel fluorescence (FL) probe 2-(4-((6-((quinolin-8-yloxy)methyl)pyridin-2-yl)methyl)piperazin-1-yl)anthracene-9,10-dione (QPPA) is designed using piperazine as a linker between the anthraquinone group, which serves as a fluorophore, and N4O as the Hg2+ ligand. The probe exhibits FL “turn-on” sensing of Hg2+ because the complex inhibits the photo-induced electron transfer (PET) process. Moreover, QPPA can overcome the invasion by other possible cations, resulting in a clear color change from orange to colorless with the addition Hg2+. The chelation of QPPA with Hg2+ in a 1:1 ratio. Subsequently, the theoretically determined binding sites of the ligand to Hg2+ are validated through 1H NMR titration. The in situQPPA–Hg2+ complex can be subjected to Hg2+ extraction following the introduction of S2− owing to its robust binding capacity. The exceptional limit of detection values for Hg2+ and S2− are obtained as 63.0 and 79.1 nM (S/N = 3), respectively. Moreover, QPPA can display bright red FL in the presence of Hg2+ in different biological specimens such as HeLa cells, zebrafish, onion root tip tissues, and water flea Daphnia carinata, further providing an effective strategy for environmental monitoring and bioimaging of Hg2+ in living organisms.

Preclinical Evaluation of a PSMA Aptamer-Based Bifunctional PET and Fluorescent Probe.

Prostate cancer is the most prevalent malignant tumor affecting male individuals worldwide. The accurate early detection of prostate cancer is crucial to preventing unnecessary diagnosis and subsequent excessive treatment. Prostate-specific membrane antigen (PSMA) has emerged as a promising biomarker for the diagnosis of prostate cancer. In this study, a dual-modality imaging probe utilizing aptamer technology was developed for positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging, and the specificity and sensitivity of the probe toward PSMA were evaluated both in vitro and in vivo. The probe precursor NOTA-PSMA-Cy5 was synthesized via automated solid-phase oligonucleotide synthesis. Subsequently, the PET/NIRF dual-modality probe [68Ga]Ga-NOTA-PSMA-Cy5 was successfully prepared and exhibited favorable fluorescence properties and stability in vitro. The binding specificity of [68Ga]Ga-NOTA-PSMA-Cy5 to PSMA was assessed through flow cytometry, fluorescence imaging, and cellular uptake experiments in LNCaP cells and PC-3 cells. In vivo PET/NIRF imaging studies demonstrated the sensitive and specific binding of [68Ga]Ga-NOTA-PSMA-Cy5 to PSMA. Overall, the PET/NIRF dual-modality probe [68Ga]Ga-NOTA-PSMA-Cy5 shows promise for the diagnosis of prostate cancer and for the fluorescence-guided identification of PSMA-positive cancer lesions during surgical procedures.

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O–OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.