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Hyun H.,Beth Israel Deaconess Medical Center | Hyun H.,Chonnam National University | Owens E.A.,Georgia State University | Wada H.,Beth Israel Deaconess Medical Center | And 9 more authors.
Angewandte Chemie - International Edition | Year: 2015

A novel class of near-infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage-specific drug development. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hyun H.,Beth Israel Deaconess Medical Center | Park M.H.,Beth Israel Deaconess Medical Center | Park M.H.,Chonnam National University | Owens E.A.,Georgia State University | And 8 more authors.
Nature Medicine | Year: 2015

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg â '1 in a pig. By using a dual-channel NIR imaging system, we observed - in real time and with high sensitivity - the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.


Park M.H.,Beth Israel Deaconess Medical Center | Park M.H.,Chonnam National University | Hyun H.,Beth Israel Deaconess Medical Center | Ashitate Y.,Beth Israel Deaconess Medical Center | And 11 more authors.
Theranostics | Year: 2014

Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection. In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection. Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further. © Ivyspring International Publisher.


Hyun H.,Beth Israel Deaconess Medical Center | Wada H.,Beth Israel Deaconess Medical Center | Bao K.,Beth Israel Deaconess Medical Center | Gravier J.,Beth Israel Deaconess Medical Center | And 7 more authors.
Angewandte Chemie - International Edition | Year: 2014

The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non-delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence-assisted resection and exploration (FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra-compact, targeted near-infrared fluorophores for various bioimaging applications is described. Bifunctional molecules with high-affinity binding to bone minerals as well as bright near-infrared fluorescence were obtained by attaching low-affinity pendant groups to the non-delocalized backbone of polymethines. These agents enable the noninvasive assessment of bone development over the course of weeks in living animals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Patent
inviCRO LLC and Curadel LLC | Date: 2016-08-31

In one embodiment, a fluorescence histo-tomography (FHT) system is disclosed. The FHT system includes a housing, a fluorescence camera located within the housing, a white light camera located within the housing, and a fluorescence light source located within the housing. The FHT system further includes a support mount configured to support the housing within a chamber of a slicing apparatus such that the cameras and fluorescence light source are aimed towards a block face of a tissue specimen retained within the chamber.


Trademark
Curadel LLC | Date: 2016-05-20

Contrast agents for use in surgical and medical imaging and visualization; Fluorescent contrast agents for use in surgical and medical imaging and visualization; Exogenous contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical and medical imaging and visualization; Exogenous near-infrared contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical procedures; Exogenous near-infrared contrast agents for use in surgical procedures; Near-infrared contrast agents for use in medical imaging and visualization; Exogenous near-infrared contrast agents for use in medical imaging and visualization; Near-infrared contrast agents for use in real-time surgical imaging and visualization; Exogenous near-infrared contrast agents for use in real-time surgical imaging and visualization, none of the foregoing being ophthalmic preparations, otorhinolaryngological preparations, or preparations for the treatment of inflammation.


Trademark
Curadel LLC | Date: 2016-05-20

Contrast agents for use in surgical and medical imaging and visualization; Fluorescent contrast agents for use in surgical and medical imaging and visualization; Exogenous contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical and medical imaging and visualization; Exogenous near-infrared contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical procedures; Exogenous near-infrared contrast agents for use in surgical procedures; Near-infrared contrast agents for use in medical imaging and visualization; Exogenous near-infrared contrast agents for use in medical imaging and visualization; Near-infrared contrast agents for use in real-time surgical imaging and visualization; Exogenous near-infrared contrast agents for use in real-time surgical imaging and visualization, none of the foregoing being ophthalmic preparations, otorhinolaryngological preparations, or preparations for the treatment of inflammation.


Trademark
Curadel LLC | Date: 2015-08-06

Contrast agents for use in surgical and medical imaging and visualization; Fluorescent contrast agents for use in surgical and medical imaging and visualization; Exogenous contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical and medical imaging and visualization; Exogenous near-infrared contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical procedures; Exogenous near-infrared contrast agents for use in surgical procedures; Near-infrared contrast agents for use in medical imaging and visualization; Exogenous near-infrared contrast agents for use in medical imaging and visualization; Near-infrared contrast agents for use in real-time surgical imaging and visualization; Exogenous near-infrared contrast agents for use in real-time surgical imaging and visualization, none of the foregoing being ophthalmic preparations, otorhinolaryngological preparations, or preparations for the treatment of inflammation. Medical and surgical equipment for use in surgical procedures, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical procedures, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit, Medical and surgical equipment for use in medical imaging and visualization, namely, visual wavelength imaging cameras, ultraviolet wavelength imaging cameras, radioscintigraphic detection hardware, optical lenses, image detectors, light sources, monitors, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras; Medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit. Tools for use in the instruction of medical imaging and visualization, namely, imaging phantoms in the nature of replications of human or animal body parts or tissue, anatomical replicas of human bodies, anatomical replicas of animal bodies, synthetic organs and tissue for instructional use. Providing consumer information in the field of cancer treatment and diagnosis via the Internet and social media. Medical and scientific research services in the field of cancer treatment and diagnosis. Providing health information in the field of cancer treatment and diagnosis via the Internet and social media.


PubMed | Leiden University, MILabs, Curadel LLC and Northwestern University
Type: Journal Article | Journal: Oncotarget | Year: 2015

Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 1.3 at 72h using fluorescence and 4.2 0.1 at 24h with radioactivity. 1-2 mm sized tumors could be clearly recognized by their fluorescent rim. This study showed the feasibility of an uPAR-recognizing multimodal agent to visualize tumors during image-guided resections using NIR fluorescence, whereas its nuclear component assisted in the pre-operative non-invasive recognition of tumors using SPECT imaging. This strategy can assist in surgical planning and subsequent precision surgery to reduce the number of incomplete resections.


Trademark
Curadel Llc and Beth Israel Deaconess Medical Center | Date: 2012-01-17

Contrast agents for use in surgical and medical imaging and visualization; Fluorescent contrast agents for use in surgical and medical imaging and visualization; Exogenous contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical and medical imaging and visualization; Exogenous near-infrared contrast agents for use in surgical and medical imaging and visualization; Near-infrared contrast agents for use in surgical procedures; Exogenous near-infrared contrast agents for use in surgical procedures; Near-infrared contrast agents for use in medical imaging and visualization; Exogenous near-infrared contrast agents for use in medical imaging and visualization; Near-infrared contrast agents for use in real-time surgical imaging and visualization; Exogenous near-infrared contrast agents for use in real-time surgical imaging and visualization, none of the foregoing being ophthalmic preparations, otorhinolaryngological preparations, or preparations for the treatment of inflammation. Medical and surgical equipment for use in surgical procedures, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical procedures, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical imaging and visualization, namely, visual wavelength imaging cameras, ultraviolet wavelength imaging cameras, radioscintigraphic detection hardware, optical lenses, image detectors, light sources, monitors, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in medical imaging and visualization, namely, cameras and near-infrared cameras; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras, and operating software used therewith, all sold as a unit; Medical and surgical equipment for use in real-time surgical imaging and visualization, namely, cameras and near-infrared cameras; Medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time medical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time surgical imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit; Real-time oncological imaging and visualization systems consisting of imaging apparatus and operating software used therewith, all sold as a unit. Tools for use in the instruction of medical imaging and visualization, namely, imaging phantoms in the nature of replications of human or animal body parts or tissue, anatomical replicas of human bodies, anatomical replicas of animal bodies, synthetic organs and tissue for instructional use.

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