scholarly journals Sensitive in vivo Visualization of Breast Cancer Using Ratiometric Protease-activatable Fluorescent Imaging Agent, AVB-620

Theranostics ◽  
2017 ◽  
Vol 7 (13) ◽  
pp. 3369-3386 ◽  
Author(s):  
Marcel Miampamba ◽  
Junjie Liu ◽  
Alec Harootunian ◽  
Andrew J Gale ◽  
Stephen Baird ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fluorescent Imaging ◽  
Imaging Agent

scholarly journals Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery

2021 ◽  
Vol 187 (1) ◽  
pp. 145-153
Author(s):  
Conor R. Lanahan ◽  
Bridget N. Kelly ◽  
Michele A. Gadd ◽  
Michelle C. Specht ◽  
Carson L. Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real Time ◽  
Imaging System ◽  
Ex Vivo ◽  
Menopausal Status ◽  
Fluorescent Imaging ◽  
Cancer Subtypes ◽  
Surgical Workflow ◽  
Tumor Types

Abstract Purpose Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20–40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. Methods We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. Results Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81–5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. Conclusions Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

Image-guided surgery for tumor agnostic detection of solid tumors using the pH-activated micellar imaging agent ONM-100.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3068-3068 ◽  
Author(s):  
Floris Jan Voskuil ◽  
Pieter Jan Steinkamp ◽  
Marjory Koller ◽  
Bert van der Vegt ◽  
Jan Johannes Doff ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Fluorescent Imaging ◽  
Activation Mechanism ◽  
Imaging Agent ◽  
Image Guided Surgery ◽  
Pharmacokinetic Data ◽  
Guided Surgery ◽  
Image Guided ◽  
Fluorescence Images

3068 Background: ONM-100, a micelle-based polymer imaging agent conjugated to indocyanine green (ICG) and with an exquisitely pH-sensitive binary activation mechanism, may be used for tumor detection. ONM-100 micelles dissociate in acidic environments resulting in activation of the fluorescent ICG tag. As nearly all solid cancer types are acidotic, ONM-100 has the potential to act as a broadly indicated tumor agnostic imaging agent. This first-in-human study investigates the safety and feasibility of ONM-100 as a tumor agnostic imaging agent for intra-operative fluorescent imaging of various solid tumors. Methods: ONM-100 was IV administered 24±8h prior to surgery in a dose escalation scheme (0.1-1.2mg/kg). Patients with histopathologically confirmed breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) and esophageal cancer (EC) were included. Blood was drawn to assess safety and pharmacokinetic data. Intra-operative fluorescence images were collected before and after tumor excision. Post-excision fluorescence images were obtained from serially sliced specimens and correlated with standard histopathological assessment. Results: 30 patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled. No ONM-100 related serious adverse events were observed and the agent was well-tolerated. A strong and sharply demarcated fluorescent signal was observed in all patients with vital tumor tissue (median CNR ranging 1.85-14.05) which correlated with tumor on final histopathology. HNSCC and superficially located BC as well as peritoneal metastasis could be clearly visualized in vivo during surgery. In four patients (BC and HNSCC), perioperatively, tumors otherwise unnoticed by the surgeons were detected on the margin or wound bed using fluorescence imaging. Additionally, two BC tumor lesions were detected that were missed by conventional pre-operative imaging and pathological assessment. Conclusions: ONM-100 appears to be safe and enables fluorescent visualization of tumors both in vivo and ex vivo. The first-in-human data demonstrate the feasibility for potential use of ONM-100 for image guided surgery, margin assessment and detection of occult disease. Clinical trial information: NTR 7085.

DEVELOPMENT OF NEEDLE-BASED MICROENDOSCOPY FOR FLUORESCENCE MOLECULAR IMAGING OF BREAST TUMOR MODELS

2009 ◽  
Vol 02 (04) ◽  
pp. 343-352
Author(s):  
CHAO-WEI CHEN ◽  
TIFFANY R. BLACKWELL ◽  
RENEE NAPHAS ◽  
PAUL T. WINNARD ◽  
VENU RAMAN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Contrast Agents ◽  
Breast Biopsy ◽  
Fluorescent Imaging ◽  
Model Systems ◽  
Breast Cancers ◽  
Imaging Device ◽  
Fluorescence Molecular Imaging

Fluorescence molecular imaging enables the visualization of basic molecular processes such as gene expression, enzyme activity, and disease-specific molecular interactions in vivo using targeted contrast agents, and therefore, is being developed for early detection and in situ characterization of breast cancers. Recent advances in developing near-infrared fluorescent imaging contrast agents have enabled the specific labeling of human breast cancer cells in mouse model systems. In synergy with contrast agent development, this paper describes a needle-based fluorescence molecular imaging device that has the strong potential to be translated into clinical breast biopsy procedures. This microendoscopy probe is based on a gradient-index (GRIN) lens interfaced with a laser scanning microscope. Specifications of the imaging performance, including the field-of-view, transverse resolution, and focus tracking characteristics were calibrated. Orthotopic MDA-MB-231 breast cancer xenografts stably expressing the tdTomato red fluorescent protein (RFP) were used to detect the tumor cells in this tumor model as a proof of principle study. With further development, this technology, in conjunction with the development of clinically applicable, injectable fluorescent molecular imaging agents, promises to perform fluorescence molecular imaging of breast cancers in vivo for breast biopsy guidance.

SNC–Coumarin is a Biocompatible Imaging Agent for In Vivo Labeling of Cells and Fluids

Nano LIFE ◽  
2015 ◽  
Vol 05 (03) ◽  
pp. 1540004 ◽  
Author(s):  
Changliang Ren ◽  
Grace Hwee Boon Ng ◽  
Xu Li ◽  
Cathleen Teh
Keyword(s):  
In Vivo Imaging ◽  
Cell Types ◽  
The Body ◽  
Fluorescent Imaging ◽  
Imaging Agent ◽  
Fluorescent Intensity ◽  
In Vivo Detection ◽  
Fabrication Procedure ◽  
Harmful Radiation

Optical imaging uses nonionizing radiation to obtain images of tissues and cells inside the body. The approach reduces exposure to harmful radiation and is suitable for lengthy and repetitive imaging procedures. Development of strongly fluorescent imaging agents will help in the detection of signal through thick tissues. Presence of such biocompatible imaging agent has potential clinical applications as it gives real-time information on disease progression and therapeutic response. We report here a nanoformulation-based strategy to synthesize a strongly fluorescent imaging agent. The fabrication procedure uses silica nanocapsules (SNC) to trap and concentrate highly fluorescent Coumarin 545T fluorophore. Biocompatibility of synthesized SNC–Coumarin was tested in cell lines and zebrafish. In vivo detection of fluorescent signal was validated in optically translucent zebrafish larvae and adult casper mutant. Nonbiased labeling of all cell types was detected in both young and adult zebrafish. The ability to differentiate fluid filled cavities from cells was also highlighted during in vivo imaging. Concomitant assessment of internalized SNC–Coumarin through acquired fluorescent intensity and associated biocompatibility in zebrafish supports its use as an in vivo imaging agent.

Water-soluble ultrasmall Eu2O3 nanoparticles as a fluorescent imaging agent: In vitro and in vivo studies

2012 ◽  
Vol 394 ◽  
pp. 85-91 ◽  
Author(s):  
Krishna Kattel ◽  
Ja Young Park ◽  
Wenlong Xu ◽  
Han Gyeol Kim ◽  
Eun Jung Lee ◽  
...  
Keyword(s):  
Fluorescent Imaging ◽  
Water Soluble ◽  
Imaging Agent ◽  
In Vivo Studies

scholarly journals Axonal Transport as an In Vivo Biomarker for Retinal Neuropathy

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1298
Author(s):  
Lucia G. Le Roux ◽  
Xudong Qiu ◽  
Megan C. Jacobsen ◽  
Mark D. Pagel ◽  
Seth T. Gammon ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Vision Loss ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Loss ◽  
Fluorescent Imaging ◽  
Imaging Agent ◽  
Imaging Biomarker ◽  
Fast Axonal Transport

We illuminate a possible explanatory pathophysiologic mechanism for retinal cellular neuropathy by means of a novel diagnostic method using ophthalmoscopic imaging and a molecular imaging agent targeted to fast axonal transport. The retinal neuropathies are a group of diseases with damage to retinal neural elements. Retinopathies lead to blindness but are typically diagnosed late, when substantial neuronal loss and vision loss have already occurred. We devised a fluorescent imaging agent based on the non-toxic C fragment of tetanus toxin (TTc), which is taken up and transported in neurons using the highly conserved fast axonal transport mechanism. TTc serves as an imaging biomarker for normal axonal transport and demonstrates impairment of axonal transport early in the course of an N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinopathy model in rats. Transport-related imaging findings were dramatically different between normal and retinopathic eyes prior to presumed neuronal cell death. This proof-of-concept study provides justification for future clinical translation.

scholarly journals 99mTc-Radiolabeled TPGS Nanomicelles Outperform 99mTc-Sestamibi as Breast Cancer Imaging Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Fiorella C. Tesan ◽  
Melisa B. Nicoud ◽  
Mariel Nuñez ◽  
Vanina A. Medina ◽  
Diego A. Chiappetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gamma Camera ◽  
Ex Vivo ◽  
Scintillation Counter ◽  
Imaging Agent ◽  
Sprague Dawley ◽  
Breast Cancer Imaging ◽  
Murine Cell Line ◽  
Polyethylene Glycol 1000

D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a Food and Drug Administration (FDA) approved biomaterial that can form nanosized micelles in aqueous solution. TPGS micelles stand as an interesting system to perform drug delivery as they can carry lipophilic drugs and overcome P glycoprotein efflux as well. Therefore, TPGS micelles combined with other copolymers have been reported in many cancer research studies as a carrier for therapeutic drugs. Their ability to reach tumoral tissue can also be exploited to develop imaging agents with diagnostic application. A radiolabeling method with 99mTc for TPGS nanosized micelles and their biodistribution in a healthy animal model as well as their pharmacokinetics and radiolabeling stability in vivo was previously reported. The aim of this work was to evaluate the performance of this radioactive probe as a diagnostic imaging agent compared to routinely available SPECT radiopharmaceutical, 99mTc-sestamibi. A small field of view gamma camera was used for scintigraphy studies using radiolabeled TPGS micelles in two animal models of breast cancer: syngeneic 4T1 murine cell line (injected in BALB/c mice) and chemically NMU-induced (Sprague-Dawley rats). Ex vivo radioactivity accumulation in organs of interest was measured by a solid scintillation counter, and a semiquantitative analysis was performed over acquired images as well. Results showed an absence of tumoral visualization in 4T1 model for both radioactive probes by gamma camera imaging. On the contrary, NMU-induced tumors had a clear tumor visualization by scintigraphy. A higher tumor/background ratio and more homogeneous uptake were found for radiolabeled TPGS micelles compared to 99mTc-sestamibi. In conclusion, 99mTc-radiolabeled TPGS micelles might be a potential SPECT imaging probe for diagnostic purposes.

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 &gt;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.

Sign in / Sign up

Export Citation Format

Share Document