The Experts below are selected from a list of 98238 Experts worldwide ranked by ideXlab platform
Hisataka Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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Fluorescent Molecular Imaging: Technical Progress and Current Preclinical and Clinical Applications in Urogynecologic Diseases
Current Molecular Medicine, 2013Co-Authors: Vinita M. Alexander, Peter L Choyke, Hisataka KobayashiAbstract:Many molecular imaging probes have been developed in recent years that hold great promise for both diagnostic and therapeutic functions in urogynecologic disease. Historically, optical probe designs were based on either endogenous or exogenous Fluorophores. More recently, organic Fluorophore probes have been engineered to target specific tissues and emit fluorescence only upon binding to targets. Several different photochemical mechanisms of activation exist. This review presents a discussion of the history and development of molecular imaging probe designs and provides an overview of successful preclinical and clinical models employing molecular probes for in vivo imaging of urogynecologic cancers.
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Fluorophore quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore−quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore−quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore−quencher pair. We selected the TAMRA (Fluorophore)−QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA−QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-...
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Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore-quencher pair. We selected the TAMRA (Fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a Fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the Fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management.
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Toxicity of organic Fluorophores used in molecular imaging: Literature review
Molecular Imaging, 2009Co-Authors: Peter L Choyke, Haley M. Simpson, Josh Duberman, G. Craig Hill, Celeste Regino, Raphael Alford, Mikako Ogawa, Hisataka KobayashiAbstract:Fluorophores are potentially useful for in vivo cancer diagnosis. Using relatively inexpensive and portable equipment, optical imaging with Fluorophores permits real-time detection of cancer. However, Fluorophores can be toxic and must be investigated before they can be administered safely to patients. A review of published literature on the toxicity of 19 widely used Fluorophores was conducted by searching 26 comprehensive biomedical and chemical literature databases and analyzing the retrieved material. These Fluorophores included Alexa Fluor 488 and 514, BODIPY FL, BODIPY R6G, Cy 5.5, Cy 7, cypate, fluorescein, indocyanine green, Oregon green, 8-phenyl BODIPY, rhodamine 110, rhodamine 6G, rhodamine X, rhodol, TAMRA, Texas red, and Tokyo green. Information regarding cytotoxicity, tissue toxicity, in vivo toxicity, and mutagenicity was included. Considerable toxicity-related information was available for the Food and Drug Administration (FDA)-approved compounds indocyanine green and fluorescein, but published information on many of the non-FDA-approved Fluorophores was limited. The information located was encouraging because the amounts of Fluorophore used in molecular imaging probes are typically much lower than the toxic doses described in the literature. Ultimately, the most effective and appropriate probes for use in patients will be determined by their fluorescent characteristics and the safety of the conjugates.
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Determination of optimal rhodamine Fluorophore for in vivo optical imaging.
Bioconjugate chemistry, 2008Co-Authors: Michelle R. Longmire, Celeste A S Regino, Yukihiro Hama, Nobuyuki Kosaka, Mikako Ogawa, Peter L Choyke, Hisataka KobayashiAbstract:Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived Fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine Fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect Fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of Fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine Fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-Fluorophore, TAMRA, is the most robust of the 4 common rhodamine Fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
Peter L Choyke - One of the best experts on this subject based on the ideXlab platform.
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Fluorescent Molecular Imaging: Technical Progress and Current Preclinical and Clinical Applications in Urogynecologic Diseases
Current Molecular Medicine, 2013Co-Authors: Vinita M. Alexander, Peter L Choyke, Hisataka KobayashiAbstract:Many molecular imaging probes have been developed in recent years that hold great promise for both diagnostic and therapeutic functions in urogynecologic disease. Historically, optical probe designs were based on either endogenous or exogenous Fluorophores. More recently, organic Fluorophore probes have been engineered to target specific tissues and emit fluorescence only upon binding to targets. Several different photochemical mechanisms of activation exist. This review presents a discussion of the history and development of molecular imaging probe designs and provides an overview of successful preclinical and clinical models employing molecular probes for in vivo imaging of urogynecologic cancers.
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Fluorophore quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore−quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore−quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore−quencher pair. We selected the TAMRA (Fluorophore)−QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA−QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-...
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Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore-quencher pair. We selected the TAMRA (Fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a Fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the Fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management.
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Toxicity of organic Fluorophores used in molecular imaging: Literature review
Molecular Imaging, 2009Co-Authors: Peter L Choyke, Haley M. Simpson, Josh Duberman, G. Craig Hill, Celeste Regino, Raphael Alford, Mikako Ogawa, Hisataka KobayashiAbstract:Fluorophores are potentially useful for in vivo cancer diagnosis. Using relatively inexpensive and portable equipment, optical imaging with Fluorophores permits real-time detection of cancer. However, Fluorophores can be toxic and must be investigated before they can be administered safely to patients. A review of published literature on the toxicity of 19 widely used Fluorophores was conducted by searching 26 comprehensive biomedical and chemical literature databases and analyzing the retrieved material. These Fluorophores included Alexa Fluor 488 and 514, BODIPY FL, BODIPY R6G, Cy 5.5, Cy 7, cypate, fluorescein, indocyanine green, Oregon green, 8-phenyl BODIPY, rhodamine 110, rhodamine 6G, rhodamine X, rhodol, TAMRA, Texas red, and Tokyo green. Information regarding cytotoxicity, tissue toxicity, in vivo toxicity, and mutagenicity was included. Considerable toxicity-related information was available for the Food and Drug Administration (FDA)-approved compounds indocyanine green and fluorescein, but published information on many of the non-FDA-approved Fluorophores was limited. The information located was encouraging because the amounts of Fluorophore used in molecular imaging probes are typically much lower than the toxic doses described in the literature. Ultimately, the most effective and appropriate probes for use in patients will be determined by their fluorescent characteristics and the safety of the conjugates.
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Determination of optimal rhodamine Fluorophore for in vivo optical imaging.
Bioconjugate chemistry, 2008Co-Authors: Michelle R. Longmire, Celeste A S Regino, Yukihiro Hama, Nobuyuki Kosaka, Mikako Ogawa, Peter L Choyke, Hisataka KobayashiAbstract:Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived Fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine Fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect Fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of Fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine Fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-Fluorophore, TAMRA, is the most robust of the 4 common rhodamine Fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
Mikako Ogawa - One of the best experts on this subject based on the ideXlab platform.
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Fluorophore quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore−quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore−quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore−quencher pair. We selected the TAMRA (Fluorophore)−QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA−QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-...
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Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore-quencher pair. We selected the TAMRA (Fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a Fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the Fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management.
-
Toxicity of organic Fluorophores used in molecular imaging: Literature review
Molecular Imaging, 2009Co-Authors: Peter L Choyke, Haley M. Simpson, Josh Duberman, G. Craig Hill, Celeste Regino, Raphael Alford, Mikako Ogawa, Hisataka KobayashiAbstract:Fluorophores are potentially useful for in vivo cancer diagnosis. Using relatively inexpensive and portable equipment, optical imaging with Fluorophores permits real-time detection of cancer. However, Fluorophores can be toxic and must be investigated before they can be administered safely to patients. A review of published literature on the toxicity of 19 widely used Fluorophores was conducted by searching 26 comprehensive biomedical and chemical literature databases and analyzing the retrieved material. These Fluorophores included Alexa Fluor 488 and 514, BODIPY FL, BODIPY R6G, Cy 5.5, Cy 7, cypate, fluorescein, indocyanine green, Oregon green, 8-phenyl BODIPY, rhodamine 110, rhodamine 6G, rhodamine X, rhodol, TAMRA, Texas red, and Tokyo green. Information regarding cytotoxicity, tissue toxicity, in vivo toxicity, and mutagenicity was included. Considerable toxicity-related information was available for the Food and Drug Administration (FDA)-approved compounds indocyanine green and fluorescein, but published information on many of the non-FDA-approved Fluorophores was limited. The information located was encouraging because the amounts of Fluorophore used in molecular imaging probes are typically much lower than the toxic doses described in the literature. Ultimately, the most effective and appropriate probes for use in patients will be determined by their fluorescent characteristics and the safety of the conjugates.
-
Determination of optimal rhodamine Fluorophore for in vivo optical imaging.
Bioconjugate chemistry, 2008Co-Authors: Michelle R. Longmire, Celeste A S Regino, Yukihiro Hama, Nobuyuki Kosaka, Mikako Ogawa, Peter L Choyke, Hisataka KobayashiAbstract:Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived Fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine Fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect Fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of Fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine Fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-Fluorophore, TAMRA, is the most robust of the 4 common rhodamine Fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
Michelle R. Longmire - One of the best experts on this subject based on the ideXlab platform.
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Fluorophore quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore−quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore−quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore−quencher pair. We selected the TAMRA (Fluorophore)−QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA−QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-...
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Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore-quencher pair. We selected the TAMRA (Fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a Fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the Fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management.
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Determination of optimal rhodamine Fluorophore for in vivo optical imaging.
Bioconjugate chemistry, 2008Co-Authors: Michelle R. Longmire, Celeste A S Regino, Yukihiro Hama, Nobuyuki Kosaka, Mikako Ogawa, Peter L Choyke, Hisataka KobayashiAbstract:Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived Fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine Fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect Fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of Fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine Fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-Fluorophore, TAMRA, is the most robust of the 4 common rhodamine Fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
Nobuyuki Kosaka - One of the best experts on this subject based on the ideXlab platform.
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Fluorophore quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore−quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore−quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore−quencher pair. We selected the TAMRA (Fluorophore)−QSY7 (quencher) pair and conjugated it to either avidin (targeting the d-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA−QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-...
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Fluorophore-quencher based activatable targeted optical probes for detecting in vivo cancer metastases
Molecular Pharmaceutics, 2009Co-Authors: Mikako Ogawa, Michelle R. Longmire, Yasuteru Urano, Nobuyuki Kosaka, Peter L Choyke, Hisataka KobayashiAbstract:In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable Fluorophores, which increased their fluorescence by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional Fluorophores. We developed an in vivo targeted activatable optical imaging probe based on a Fluorophore-quencher pair, bound to a targeting moiety. With this system, fluorescence is quenched by the Fluorophore-quencher interaction outside cancer cells, but is activated within the target cells by dissociation of the Fluorophore-quencher pair. We selected the TAMRA (Fluorophore)-QSY7 (quencher) pair and conjugated it to either avidin (targeting the D-galactose receptor) or trastuzumab (a monoclonal antibody against the human epithelial growth factor receptor type2 (HER2/neu)) and evaluated their performance in mouse models of cancer. Two probes, TAMRA-QSY7 conjugated avidin (Av-TM-Q7) and trastuzumab (Traz-TM-Q7) were synthesized. Both demonstrated better than similar self-quenching probes. In vitro fluorescence microscopic studies of SHIN3 and NIH/3T3/HER2+ cells demonstrated that Av-TM-Q7 and Traz-TM-Q7 produced high intracellular fluorescent signal. In vivo imaging with Av-TM-Q7 and Traz-TM-Q7 in mice enabled the detection of small tumors. This molecular imaging probe, based on a Fluorophore-quencher pair conjugated to a targeting ligand, successfully detected tumors in vivo due to its high activation ratio and low background signal. Thus, these activatable probes, based on the Fluorophore-quencher system, hold promise clinically for "see and treat" strategies of cancer management.
-
Determination of optimal rhodamine Fluorophore for in vivo optical imaging.
Bioconjugate chemistry, 2008Co-Authors: Michelle R. Longmire, Celeste A S Regino, Yukihiro Hama, Nobuyuki Kosaka, Mikako Ogawa, Peter L Choyke, Hisataka KobayashiAbstract:Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived Fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine Fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect Fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of Fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine Fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-Fluorophore, TAMRA, is the most robust of the 4 common rhodamine Fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
