scholarly journals Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 370
Author(s):  
Tina Fonnes ◽  
Elin Strand ◽  
Kristine E. Fasmer ◽  
Hege F. Berg ◽  
Heidi Espedal ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Near Infrared ◽  
Imaging Modality ◽  
Therapy Monitoring ◽  
Fluorescent Imaging ◽  
Therapeutic Development ◽  
Spatio Temporal ◽  
Preclinical Animal Models ◽  
Pdx Models

Imaging of clinically relevant preclinical animal models is critical to the development of personalized therapeutic strategies for endometrial carcinoma. Although orthotopic patient-derived xenografts (PDXs) reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by the lack of appropriate imaging modalities. Here, we describe molecular imaging of a near-infrared fluorescently labeled monoclonal antibody targeting epithelial cell adhesion molecule (EpCAM) as an in vivo imaging modality for visualization of orthotopic endometrial carcinoma PDX. Application of this near-infrared probe (EpCAM-AF680) enabled both spatio-temporal visualization of development and longitudinal therapy monitoring of orthotopic PDX. Notably, EpCAM-AF680 facilitated imaging of multiple PDX models representing different subtypes of the disease. Thus, the combined implementation of EpCAM-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform for identification and validation of new targeted therapies and corresponding response predicting markers for endometrial carcinoma.

Evaluation of Red CdTe and Near Infrared CdHgTe Quantum Dots by Fluorescent Imaging

2008 ◽  
Vol 8 (3) ◽  
pp. 1155-1159 ◽  
Author(s):  
Jun Zhang ◽  
Junfeng Su ◽  
Li Liu ◽  
Yalou Huang ◽  
Ralph P. Mason
Keyword(s):  
Fluorescent Probes ◽  
Near Infrared ◽  
Fluorescent Imaging ◽  
Tissue Imaging ◽  
Antibody Conjugates ◽  
Deep Tissue Imaging ◽  
Membrane Antigens ◽  
Preclinical Animal Models

Non-invasive fluorescent imaging of preclinical animal models in vivo is a rapidly developing field with new emerging technologies and techniques. Quantum dot (QD) fluorescent probes with longer emission wavelengths in red and near infrared (NIR) emission ranges are more amenable to deep-tissue imaging, because both scattering and autofluorescence are reduced as wavelengths are increased. We have designed and synthesized red CdTe and NIR CdHgTe QDs for fluorescent imaging. We demonstrated fluorescent imaging by using CdTe and CdHgTe QDs as fluorescent probes both in vitro and in vivo. Both CdTe and CdHgTe QDs provided sensitive detection over background autofluorescence in tissue biopsies and live mice, making them attractive probes for in vivo imaging extending into deep tissues or whole animals. The studies suggest a basis of using QD-antibody conjugates to detect membrane antigens.

Fluorescent proteins for in vivo imaging, where's the biliverdin?

2020 ◽  
Vol 48 (6) ◽  
pp. 2657-2667
Author(s):  
Felipe Montecinos-Franjola ◽  
John Y. Lin ◽  
Erik A. Rodriguez
Keyword(s):  
Hydrogen Peroxide ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Fluorescent Imaging ◽  
Infrared Light ◽  
Red Fluorescent Protein ◽  
Color Palette

Noninvasive fluorescent imaging requires far-red and near-infrared fluorescent proteins for deeper imaging. Near-infrared light penetrates biological tissue with blood vessels due to low absorbance, scattering, and reflection of light and has a greater signal-to-noise due to less autofluorescence. Far-red and near-infrared fluorescent proteins absorb light >600 nm to expand the color palette for imaging multiple biosensors and noninvasive in vivo imaging. The ideal fluorescent proteins are bright, photobleach minimally, express well in the desired cells, do not oligomerize, and generate or incorporate exogenous fluorophores efficiently. Coral-derived red fluorescent proteins require oxygen for fluorophore formation and release two hydrogen peroxide molecules. New fluorescent proteins based on phytochrome and phycobiliproteins use biliverdin IXα as fluorophores, do not require oxygen for maturation to image anaerobic organisms and tumor core, and do not generate hydrogen peroxide. The small Ultra-Red Fluorescent Protein (smURFP) was evolved from a cyanobacterial phycobiliprotein to covalently attach biliverdin as an exogenous fluorophore. The small Ultra-Red Fluorescent Protein is biophysically as bright as the enhanced green fluorescent protein, is exceptionally photostable, used for biosensor development, and visible in living mice. Novel applications of smURFP include in vitro protein diagnostics with attomolar (10−18 M) sensitivity, encapsulation in viral particles, and fluorescent protein nanoparticles. However, the availability of biliverdin limits the fluorescence of biliverdin-attaching fluorescent proteins; hence, extra biliverdin is needed to enhance brightness. New methods for improved biliverdin bioavailability are necessary to develop improved bright far-red and near-infrared fluorescent proteins for noninvasive imaging in vivo.

scholarly journals Intravascular Molecular Imaging: Near-Infrared Fluorescence as a New Frontier

2020 ◽  
Vol 7 ◽  
Author(s):  
Haitham Khraishah ◽  
Farouc A. Jaffer
Keyword(s):  
Near Infrared ◽  
Imaging Modality ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Endothelial Permeability ◽  
Intravascular Imaging ◽  
Near Infrared Fluorescence ◽  
New Era ◽  
Nirf Imaging

Despite exciting advances in structural intravascular imaging [intravascular ultrasound (IVUS) and optical coherence tomography (OCT)] that have enabled partial assessment of atheroma burden and high-risk features associated with acute coronary syndromes, structural-based imaging modalities alone do not comprehensively phenotype the complex pathobiology of atherosclerosis. Near-infrared fluorescence (NIRF) is an emerging molecular intravascular imaging modality that allows for in vivo visualization of pathobiological and cellular processes at atheroma plaque level, including inflammation, oxidative stress, and abnormal endothelial permeability. Established intravascular NIRF imaging targets include macrophages, cathepsin protease activity, oxidized low-density lipoprotein and abnormal endothelial permeability. Structural and molecular intravascular imaging provide complementary information about plaque microstructure and biology. For this reason, integrated hybrid catheters that combine NIRF-IVUS or NIRF-OCT have been developed to allow co-registration of morphological and molecular processes with a single pullback, as performed for standalone IVUS or OCT. NIRF imaging is approaching application in clinical practice. This will be accelerated by the use of FDA-approved indocyanine green (ICG), which illuminates lipid- and macrophage-rich zones of permeable atheroma. The ability to comprehensively phenotype coronary pathobiology in patients will enable a deeper understanding of plaque pathobiology, improve local and patient-based risk prediction, and usher in a new era of personalized therapy.

scholarly journals J-Aggregates of meso- [2.2] Paracyclophanyl-BODIPY Dye for NIR-II Imaging

2020 ◽  
Author(s):  
Zhipeng Liu ◽  
Kang Li ◽  
Xingchen Duan ◽  
Zhiyong Jiang ◽  
Dan Ding ◽  
...  
Keyword(s):  
Near Infrared ◽  
Organic Dyes ◽  
Fluorescent Imaging ◽  
Imaging Agents ◽  
Aggregation State ◽  
Guided Surgery ◽  
Lymph Node Imaging ◽  
Diluted Solution ◽  
J Aggregates

Abstract J-aggregation has been proved to be an efficient strategy for the development of fluorescent imaging agents in the second near-infrared (NIR-II, 1000–1700 nm) window. However, the design of NIR-II fluorescent J-aggregates is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso-[2.2]paracyclophanyl-3,5-bis-N,N-dimethylaminostyrl BODIPY (PCP-BDP2) as the first example of BODIPY dye with J-aggregation induced NIR-II fluorescence. PCP-BDP2 shows emission maximum at 795 nm in diluted solution and NIR-II emission at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY core plays key roles in the J-aggregation behavior and NIR-II fluorescence tuning. Notably, NIR-II emissive J-aggregates of PCP-BDP2 can be efficiently stabilized in the assembled nanoparticle. Taking advantage of high quantum yield and good photo-/chemo-stability, J-aggregates of PCP-BDP2 show high-resolution and long-term in vivo NIR-II imaging ability. Furthermore, J-aggregates of PCP-BDP2 can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study not only demonstrates BODIPY dye as a new J-aggregation platform for developing NIR-II imaging agents but also encourages further exploration on J-aggregation induced NIR-II emission of the other conventional organic dyes.

scholarly journals Characterization of residual lipid-rich plaques despite achieving LDL-C <1.8mmol/l with a statin in patients with coronary artery disease: insights from the REASSURE-NIRS registry

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Kitahara ◽  
Y Kataoka ◽  
T Iwai ◽  
K Sawada ◽  
H Matama ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Near Infrared ◽  
Imaging Modality ◽  
Statistical Significance ◽  
Lipid Lowering ◽  
Residual Lipid ◽  
Artery Disease ◽  
Stable Cad

Abstract Introduction Recent studies have demonstrated favourable modification of lipidic plaque materials under achieving LDL-C &lt;1.8mmol/l with a statin, which potentially accounts for its clinical benefit. However, coronary events still occur even under optimal LDL-C management. This may suggest the presence of residual lipid-rich coronary plaque despite on-treatment LDL-C &lt;1.8mmol/l. Given that near-infrared spectroscopy (NIRS) enables quantitative evaluation of lipidic plaque in vivo, we employed this imaging modality to investigate characteristics and drivers of residual lipid-rich plaques in statin-treated patients with coronary artery disease (CAD) who achieved LDL-C &lt;1.8mmol/l. Purpose To clarify the frequency, clinical demographics and factors associated with residual lipid-rich plaques under LDL-C &lt;1.8mmol/l. Methods The REASSURE-NIRS registry is an on-going multi-center registry to enroll CAD subjects receiving NIRS/intravascular ultrasound-guided PCI. The current analysis included 133 statin-treated stable CAD patients with on-treatment LDL-C &lt;1.8mmol/l from August 2015 to December 2020. The maximum 4-mm lipid core burden index (maxLCBI4mm) at culprit lesions was measured by NIRS imaging prior to PCI. Clinical characteristics were compared in patients with and without maxLCBI4mm ≥400 at culprit lesions. Results In the current study, 45% (=58/128) of study subjects exhibited maxLCBI4mm ≥400 at culprit lesions under on-treatment LDL-C &lt;1.8 mmol/l. They were more likely to be female, whereas there were no differences in age and the frequency of risk factors. Most of study subjects received moderate to high-intensity statin (p=0.79), and over one-fourth of them were treated with ezetimibe (p=0.56). Under these lipid-lowering therapies, LDL-C level was significantly higher in patients with maxLCBI4mm ≥400 (Table). Additionally, a lower frequency of LDL-C &lt;1.4mmol/l was observed in those exhibiting maxLCBI4mm ≥400 (31.0 vs. 45.7%), but this comparison failed to meet statistical significance (p=0.09). Despite LDL-C control with a statin, deterioration of coronary flow after PCI with stent implantation more frequently occurred in patients with maxLCBI4mm ≥400 (Table). Multivariate analysis demonstrated that an independent factor associated with maxLCBI4mm ≥400 was LDL-C level (OR=1.05; 95% CI=1.00–1.10, p=0.03), but not other lipid and clinical parameters. Conclusion Almost half of CAD subjects who achieved LDL-C level &lt;1.8mmol/l still exhibited the accumulation of lipidic plaque materials within vessel wall. Given that LDL-C level was associated with this residual lipid-rich plaque features, our findings support current ESC-guideline recommended LDL-C goal (&lt;1.4mmol/l) to optimize the secondary prevention in stable CAD patients. Funding Acknowledgement Type of funding sources: None.

scholarly journals Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Extent Of Resection ◽  
Fluorescent Imaging ◽  
Control Group ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Specific Accumulation

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

Porous Hollow Gold Nanoparticles for Cancer SERS Imaging

2010 ◽  
Vol 10 ◽  
pp. 137-148 ◽  
Author(s):  
Chien Wen Huang ◽  
Yao Wu Hao ◽  
James Nyagilo ◽  
Digant P. Dave ◽  
Li Feng Xu ◽  
...  
Keyword(s):  
Large Scale ◽  
Near Infrared ◽  
Au Nanoparticles ◽  
Imaging Modality ◽  
Surface Enhanced Raman Spectroscopy ◽  
Au Nanoparticle ◽  
Resonant Effect ◽  
Surface Enhanced Raman ◽  
Sers Imaging

Surface enhanced Raman spectroscopy (SERS) is a promising molecular imaging modality capable of simultaneously detecting multiple molecular biomarkers. With the biocompatibility and functionalizability of Au, Au-nanoparticle based Raman tags possess the potential for in vivo SERS cancer biomarker detection. Here, we report the large scale synthesis of a new type of Au nanoparticles, Porous Hollow Au Nanoparticles (PHAuNPs), and demonstrate their potential application as SERS imaging tags. PHAuNPs feature a sub-20 nm porous shell and a 50 nm void core. Such unique morphology enables them to strongly absorb and scatter near infrared lights due to the surface plasmon resonant effect of Au. This makes them particularly suitable for in vivo applications, where NIR wavelengths are considered as a ‘clear window’ for deeper penetration of light. The construction and characterization of PHAuNP-based Raman nanotag, including attachment of Raman dye, pegylation and their stability, are described. Cytotoxicity of Raman nanotags are tested using the radioactive [3H]thymidine incorporation method. The results show that pegylated Raman nanotags are stable and non-toxic and can potentially be used for in vivo applications.

Programmably switching the NIR upconversion for orthogonal activation of photoacoustic imaging and on-demand phototherapy

2021 ◽  
Author(s):  
Yang Yang ◽  
Jinshu Huang ◽  
Wei Wei ◽  
Qin Zeng ◽  
Xipeng Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Continuous Wave ◽  
Photoacoustic Imaging ◽  
Imaging Modality ◽  
Infrared Emission ◽  
Imaging Diagnostics ◽  
On Demand ◽  
Personalized Cancer

Abstract Upconversion nanoparticles (UCNPs) based phototheranostics offer significant expectations for the personalized cancer medicine via integrating both modalities of imaging diagnostics and phototherapeutics. However, programmably controlling the photoactivation of imaging and therapy towards the accurate diagnosis with minimum side effects for on-demand therapy has remained challenging due to the lack of ideal switchable UCNPs agents. Herein, we demonstrate a facile strategy to simply switch the near infrared emission at 800 nm from rationally designed UCNPs by modulating the irradiation laser into pulse output. Through synthesis of the theranostic UCNPs-DI agent combining with a photosensitizer and a photoabsorbing agent assembled on the UCNPs, the orthogonal activation of in vivo photoacoustic imaging and photodynamic therapy was further achieved by simply altering the excitation modes from pulse to continuous-wave output upon a single 980-nm laser. Importantly, no obvious harmful effects during photoexcitation caused by reactive oxygen species (ROS) photooxidation and photohyperthermia were generated under imaging modality, which facilitates the long-term and real-time imaging-guidance for the subsequent phototherapy. This work provides a new facile approach for the orthogonal activation of imaging diagnostics and photodynamic therapeutics towards the target cancers.

Upconversion Luminescence Imaging of Tumors with EGFR-Affibody Conjugated Nanophosphors

MRS Advances ◽  
2019 ◽  
Vol 4 (46-47) ◽  
pp. 2461-2470 ◽  
Author(s):  
Majid Badieirostami ◽  
Colin Carpenter ◽  
Guillem Pratx ◽  
Lei Xing ◽  
Conroy Sun
Keyword(s):  
Near Infrared ◽  
Imaging System ◽  
Imaging Modality ◽  
Photophysical Properties ◽  
Upconversion Luminescence ◽  
Detection Sensitivity ◽  
Photon Absorption ◽  
Great Promise

ABSTRACTNear infrared (NIR) optical imaging has demonstrated significant potential as an effective modality for cancer molecular imaging. Among various NIR probes currently under investigation, upconversion nanophosphors (UCNPs) possess great promise due to their anti-Stokes emission and sequential photon absorption which result in superior detection sensitivity and a simple imaging setup, respectively. Here we investigated the utility of this imaging modality to detect tumor cells expressing the epidermal growth factor receptor (EGFR) using affibody functionalized nanophosphors and a custom built imaging system. Initially, aqueous dispersible NaYF4: Tm+3, Yb+3 UCNPs were synthesized and their photophysical properties were characterized. Then, their luminescence response as a function of concentration and their depth resolving capability in a tissue-simulating phantom were examined. Finally, we demonstrated the use of bioconjugated UCNPs for imaging EGFR-expressing tumors both in vitro and in vivo. Our data suggests that NIR imaging with UCNPs may be useful for noninvasive imaging of tumors.

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