A proof-of-concept application of water-soluble ytterbium(iii) molecular probes in in vivo NIR-II whole body bioimaging

Oxidative stress, defined as a misbalance between the production of reactive oxygen species and the antioxidant defenses of the cell, appears as a critical factor either in the onset or in the etiology of many pathological conditions. Several methods of detection exist. However, they usually rely on ex vivo evaluation or reports on the status of living tissues only up to a few millimeters in depth, while a whole-body, real-time, non-invasive monitoring technique is required for early diagnosis or as an aid to therapy (to monitor the action of a drug). Methods based on electron paramagnetic resonance (EPR), in association with molecular probes based on aminoxyl radicals (nitroxides) or hydroxylamines especially, have emerged as very promising to meet these standards. The principles involve monitoring the rate of decrease or increase of the EPR signal in vivo after injection of the nitroxide or the hydroxylamine probe, respectively, in a pathological versus a control situation. There have been many successful applications in various rodent models. However, current limitations lie in both the field of the technical development of the spectrometers and the molecular probes. The scope of this review will mainly focus on the latter.

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Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters

Bioengineering ◽

10.3390/bioengineering7010020 ◽

2020 ◽

Vol 7 (1) ◽

pp. 20 ◽

Cited By ~ 6

Author(s):

Suresh Thangudu ◽

Poliraju Kalluru ◽

Raviraj Vankayala

Keyword(s):

In Vitro Cytotoxicity ◽

Molecular Probes ◽

Water Soluble ◽

Quantum Yields ◽

Cell Labelling ◽

Metal Nanoclusters ◽

Extinction Coefficients ◽

Cytotoxicity Studies

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.

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Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging for Coronavirus Disease 2019

Frontiers in Immunology ◽

10.3389/fimmu.2021.568959 ◽

2021 ◽

Vol 12 ◽

Author(s):

Freimut D. Juengling ◽

Antonio Maldonado ◽

Frank Wuest ◽

Thomas H. Schindler

Keyword(s):

Molecular Imaging ◽

Current Knowledge ◽

Imaging Modality ◽

Acute Infection ◽

Molecular Probes ◽

Whole Body ◽

Prognostic Indicators ◽

Imaging Biomarkers ◽

Body Scale

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering in-vivo imaging and quantitation of key pathophysiological targets or molecular signatures, such as glucose metabolism in cancerous disease. Apart from metabolism probes, novel radiolabeled peptide and antibody PET tracers, including radiolabeled monoclonal antibodies (mAbs) have entered the clinical arena, providing the in-vivo capability to collect target-specific quantitative in-vivo data on cellular and molecular pathomechanisms on a whole-body scale, and eventually, extract imaging biomarkers possibly serving as prognostic indicators. The success of molecular imaging in mapping disease severity on a whole-body scale, and directing targeted therapies in oncology possibly could translate to the management of Coronavirus Disease 2019 (COVID-19), by identifying, localizing, and quantifying involvement of different immune mediated responses to the infection with SARS-COV2 during the course of acute infection and possible, chronic courses with long-term effects on specific organs. The authors summarize current knowledge for medical imaging in COVID-19 in general with a focus on molecular imaging technology and provide a perspective for immunologists interested in molecular imaging research using validated and immediately available molecular probes, as well as possible future targets, highlighting key targets for tailored treatment approaches as brought up by key opinion leaders.

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In Vivo Resolution of Multiexponential Decays of Multiple Near-Infrared Molecular Probes by Fluorescence Lifetime-Gated Whole-Body Time-Resolved Diffuse Optical Imaging

Molecular Imaging ◽

10.2310/7290.2007.00020 ◽

2007 ◽

Vol 6 (4) ◽

pp. 7290.2007.00020 ◽

Cited By ~ 31

Author(s):

Walter Akers ◽

Frederic Lesage ◽

Dewey Holten ◽

Samuel Achilefu

Keyword(s):

Optical Imaging ◽

Fluorescence Lifetime ◽

Fluorescence Intensity ◽

Near Infrared ◽

Molecular Probes ◽

Whole Body ◽

Diffuse Optical Imaging ◽

Fluorescence Lifetimes ◽

Time Resolved

The biodistribution of two near-infrared fluorescent agents was assessed in vivo by time-resolved diffuse optical imaging. Bacteriochlorophyll a (BC) and cypate-glysine-arginine-aspartic acid-serine-proline-lysine-OH (Cyp-GRD) were administered separately or combined to mice with subcutaneous xenografts of human breast adenocarcinoma and slow-release estradiol pellets for improved tumor growth. The same excitation (780 nm) and emission (830 nm) wavelengths were used to image the distinct fluorescence lifetime distribution of the fluorescent molecular probes in the mouse cancer model. Fluorescence intensity and lifetime maps were reconstructed after raster-scanning whole-body regions of interest by time-correlated single-photon counting. Each captured temporal point-spread function (TPSF) was deconvolved using both a single and a multiexponental decay model to best determine the measured fluorescence lifetimes. The relative signal from each fluorophore was estimated for any region of interest included in the scanned area. Deconvolution of the individual TPSFs from whole-body fluorescence intensity scans provided corresponding lifetime images for comparing individual component biodistribution. In vivo fluorescence lifetimes were determined to be 0.8 ns (Cyp-GRD) and 2 ns (BC). This study demonstrates that the relative biodistribution of individual fluorophores with similar spectral characteristics can be compartmentalized by using the time-domain fluorescence lifetime gating method.

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Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe

Circulation ◽

10.1161/circ.142.suppl_3.14935 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Dong Oh Kang ◽

Yong Geun Lim ◽

Joon Woo Song ◽

Ye Hee Park ◽

Hyun Jung Kim ◽

...

Keyword(s):

Molecular Imaging ◽

High Resolution ◽

Murine Model ◽

Calcium Binding ◽

Laser Scanning ◽

Near Infrared ◽

Imaging System ◽

Whole Body ◽

Imaging Results

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p<0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p<0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.

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High-resolution magnetic resonance imaging tracks changes in organ and tissue mass in obese and aging rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.0527.2001 ◽

2002 ◽

Vol 282 (3) ◽

pp. R890-R899 ◽

Cited By ~ 34

Author(s):

Haiying Tang ◽

Joseph R. Vasselli ◽

Ed X. Wu ◽

Carol N. Boozer ◽

Dympna Gallagher

Keyword(s):

Magnetic Resonance Imaging ◽

Adipose Tissue ◽

Magnetic Resonance ◽

High Resolution ◽

Soft Tissues ◽

Whole Body ◽

Resonance Imaging ◽

Sprague Dawley ◽

Tissue Mass

Magnetic resonance imaging (MRI) has the ability to discriminate between various soft tissues in vivo. Whole body, specific organ, total adipose tissue (TAT), intra-abdominal adipose tissue (IAAT), and skeletal muscle (SM) weights determined by MRI were compared with weights determined by dissection and chemical analysis in two studies with male Sprague-Dawley rats. A 4.2-T MRI machine acquired high-resolution, in vivo, longitudinal whole body images of rats as they developed obesity or aged. Weights of the whole body and specific tissues were determined using computer image analysis software, including semiautomatic segmentation algorithms for volume calculations. High correlations were found for body weight ( r = 0.98), TAT ( r = 0.99), and IAAT ( r = 0.98) between MRI and dissection and chemical analyses. MRI estimated the weight of the brain, kidneys, and spleen with high accuracy ( r > 0.9), but overestimated IAAT, SM, and liver volumes. No differences were detected in organ weights using MRI and dissection measurements. Longitudinal MRI measurements made during the development of obesity and aging accurately represented changes in organ and tissue mass.

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A Novel Receive-Only Liquid Nitrogen ($\hbox{LN}_{2}$ )-Cooled RF Coil for High-Resolution In Vivo Imaging on a 3-Tesla Whole-Body Scanner

IEEE Transactions on Instrumentation and Measurement ◽

10.1109/tim.2011.2157575 ◽

2012 ◽

Vol 61 (1) ◽

pp. 129-139 ◽

Cited By ~ 13

Author(s):

Bobo Hu ◽

Gopal Varma ◽

Chris Randell ◽

Stephen F. Keevil ◽

Tobias Schaeffter ◽

...

Keyword(s):

High Resolution ◽

Liquid Nitrogen ◽

In Vivo Imaging ◽

3 Tesla ◽

Whole Body ◽

Rf Coil ◽

Body Scanner

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Cross-validation study between the HRRT and the PET component of the SIGNA PET/MRI system with focus on neuroimaging

EJNMMI Physics ◽

10.1186/s40658-020-00349-0 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Julia G. Mannheim ◽

Ju-Chieh (Kevin) Cheng ◽

Nasim Vafai ◽

Elham Shahinfard ◽

Carolyn English ◽

...

Keyword(s):

High Resolution ◽

Brain Imaging ◽

Validation Study ◽

Cross Validation ◽

Whole Body ◽

Line Profiles ◽

Time Activity ◽

Phantom Data ◽

Two Systems

Abstract Background The Siemens high-resolution research tomograph (HRRT - a dedicated brain PET scanner) is to this day one of the highest resolution PET scanners; thus, it can serve as useful benchmark when evaluating performance of newer scanners. Here, we report results from a cross-validation study between the HRRT and the whole-body GE SIGNA PET/MR focusing on brain imaging. Phantom data were acquired to determine recovery coefficients (RCs), % background variability (%BG), and image voxel noise (%). Cross-validation studies were performed with six healthy volunteers using [11C]DTBZ, [11C]raclopride, and [18F]FDG. Line profiles, regional time-activity curves, regional non-displaceable binding potentials (BPND) for [11C]DTBZ and [11C]raclopride scans, and radioactivity ratios for [18F]FDG scans were calculated and compared between the HRRT and the SIGNA PET/MR. Results Phantom data showed that the PET/MR images reconstructed with an ordered subset expectation maximization (OSEM) algorithm with time-of-flight (TOF) and TOF + point spread function (PSF) + filter revealed similar RCs for the hot spheres compared to those obtained on the HRRT reconstructed with an ordinary Poisson-OSEM algorithm with PSF and PSF + filter. The PET/MR TOF + PSF reconstruction revealed the highest RCs for all hot spheres. Image voxel noise of the PET/MR system was significantly lower. Line profiles revealed excellent spatial agreement between the two systems. BPND values revealed variability of less than 10% for the [11C]DTBZ scans and 19% for [11C]raclopride (based on one subject only). Mean [18F]FDG ratios to pons showed less than 12% differences. Conclusions These results demonstrated comparable performances of the two systems in terms of RCs with lower voxel-level noise (%) present in the PET/MR system. Comparison of in vivo human data confirmed the comparability of the two systems. The whole-body GE SIGNA PET/MR system is well suited for high-resolution brain imaging as no significant performance degradation was found compared to that of the reference standard HRRT.

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Imaging-Guided Evaluation of the Novel Small-Molecule Benzosuberene Tubulin-Binding Agent KGP265 as a Potential Therapeutic Agent for Cancer Treatment

Cancers ◽

10.3390/cancers13194769 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4769

Author(s):

Yihang Guo ◽

Honghong Wang ◽

Jeni L. Gerberich ◽

Samuel O. Odutola ◽

Amanda K. Charlton-Sevcik ◽

...

Keyword(s):

Tumor Growth ◽

Water Soluble ◽

Whole Body ◽

Growth Delay ◽

Binding Agent ◽

Tumor Growth Delay ◽

Kidney Tumors ◽

In Vivo Evaluation ◽

Tubulin Binding

The selective disruption of tumor-associated vasculature represents an attractive therapeutic approach. We have undertaken the first in vivo evaluation of KGP265, a water-soluble prodrug of a benzosuberene-based tubulin-binding agent, and found promising vascular-disrupting activity in three distinct tumor types. Dose escalation in orthotopic MDA-MB-231-luc breast tumor xenografts in mice indicated that higher doses produced more effective vascular shutdown, as revealed by dynamic bioluminescence imaging (BLI). In syngeneic orthotopic 4T1-luc breast and RENCA-luc kidney tumors, dynamic BLI and oxygen enhanced multispectral optoacoustic tomography (OE-MSOT) were used to compare vascular shutdown following the administration of KGP265 (7.5 mg/kg). The BLI signal and vascular oxygenation response (ΔsO2) to a gas breathing challenge were both significantly reduced within 2 h, indicating vascular disruption, which continued over 24 h. A correlative histology confirmed increased necrosis and hemorrhage. Twice-weekly doses of KGP265 caused significant growth delay in both MDA-MB-231 and 4T1 breast tumors, with no obvious systemic toxicity. A combination with carboplatin produced significantly greater tumor growth delay than carboplatin alone, though significant carboplatin-associated toxicity was observed (whole-body weight loss). KGP265 was found to be effective at low concentrations, generating long-term vascular shutdown and tumor growth delay, thus providing strong rationale for further development, particularly in combination therapies.

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