The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Ralph Weissleder - One of the best experts on this subject based on the ideXlab platform.
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Meeting report: high-throughput technologies for in vivo Imaging Agents.
Molecular Imaging, 2020Co-Authors: Robert J. Gillies, John M. Hoffman, Anne E. Menkens, David Piwnica-worms, Daniel C. Sullivan, Ralph WeisslederAbstract:Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo Imaging Agents. Important differences in the biological and pharmacological properties needed for Imaging Agents, compared to those for a therapeutic Agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good Imaging Agent candidate.
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supercritical fluid assisted one pot synthesis of biocompatible core γ fe2o3 shell sio2 nanoparticles as high relaxivity t2 contrast Agents for magnetic resonance Imaging
Advanced Functional Materials, 2009Co-Authors: Elena Taboada, Raul Solanas, Elisenda Rodríguez, Ralph Weissleder, Asunción RoigAbstract:Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(γ-Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol–gel chemistry and supercritical fluid technology. This one-step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T2 MRI Imaging Agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.
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Supercritical-Fluid-Assisted One-Pot Synthesis of Biocompatible Core( γ -Fe 2 O 3 )/Shell(SiO 2 ) Nanoparticles as High Relaxivity T 2 -Contrast Agents for Magnetic Resonance Imaging
Advanced Functional Materials, 2009Co-Authors: Elena Taboada, Raul Solanas, Elisenda Rodríguez, Ralph Weissleder, Asunción RoigAbstract:Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(γ-Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol–gel chemistry and supercritical fluid technology. This one-step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T2 MRI Imaging Agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.
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detection of early prostate cancer using a hepsin targeted Imaging Agent
Cancer Research, 2008Co-Authors: Kimberly A Kelly, Sunita R Setlur, Robert S Ross, Rajesh Anbazhagan, Peter Waterman, Mark A Rubin, Ralph WeisslederAbstract:Early detection and diagnosis of prostate cancer is key to designing effective treatment strategies. Microarrays have resulted in the discovery of hepsin (HPN) as a biomarker for detection of prostate cancer. In this study, we explore the development of HPN Imaging probes for detection of prostate cancer. We used phage display to isolate HPN binding peptides with 190 + 2.2 nmol/L affinity in monomeric form and high specificity. The identified peptides were able to detect human prostate cancer on tissue microarrays and in cell-based assays. HPN-targeted Imaging Agents were synthesized by conjugating multiple peptides to fluorescent nanoparticles to further improve avidity through multivalency and to improve pharmacokinetics. When injected into mouse xenograft models, HPN-targeted nanoparticles bound specifically to HPN-expressing LNCaP xenografts compared with non-HPN-expressing PC3 xenografts. HPN Imaging may provide a new method for detection of prostate cancer.
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optical visualization of cathepsin k activity in atherosclerosis with a novel protease activatable fluorescence sensor
Circulation, 2007Co-Authors: Farouc A Jaffer, Luisa Quinti, Chinghsuan Tung, Elena Aikawa, Ashvin N Pande, Rainer H Kohler, Peter Libby, Ralph WeisslederAbstract:Background— Cathepsin K (CatK), a potent elastinolytic and collagenolytic cysteine protease, likely participates in the evolution and destabilization of atherosclerotic plaques. To assess better the biology of CatK activity in vivo, we developed a novel near-infrared fluorescence (NIRF) probe for Imaging of CatK and evaluated it in mouse and human atherosclerosis. Methods and Results— The NIRF Imaging Agent consists of the CatK peptide substrate GHPGGPQGKC-NH2 linked to an activatable fluorogenic polymer. In vitro, CatK produced a 2- to 14-fold activation of the Agent over other cysteine and matrix metalloproteinases (P 8-fold activation over a control Imaging Agent (P 100% NIRF signal increases in apolipoprotein E−/− mice in vivo (n=13; P<0.05, CatK Imaging Agent versus control Agent) and in human carotid endarterectomy specimens ex vivo (n=14; P<0.05). Fluorescence microscopy of plaque sections demonstrated that enzymatically active Ca...
Sanjeeb K Sahoo - One of the best experts on this subject based on the ideXlab platform.
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multifunctional nanoparticle epcam aptamer bioconjugates a paradigm for targeted drug delivery and Imaging in cancer therapy
Nanomedicine: Nanotechnology Biology and Medicine, 2015Co-Authors: Manasi Das, Wei Duan, Sanjeeb K SahooAbstract:Abstract The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and Imaging Agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an Imaging Agent (quantum dots) for cancer therapy and bioImaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-Imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy. From the Clinical Editor This study investigated the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles functionalized with a targeting ligand (EpCAM aptamer) and an Imaging Agent (quantum dots) for cancer therapy and bioImaging. It was concluded that the studied multifunctional targeted nanoparticle may become a viable and efficient approach in cancer therapy.
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Multifunctional nanoparticle–EpCAM aptamer bioconjugates: A paradigm for targeted drug delivery and Imaging in cancer therapy
Nanomedicine: Nanotechnology Biology and Medicine, 2014Co-Authors: Manasi Das, Wei Duan, Sanjeeb K SahooAbstract:Abstract The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and Imaging Agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an Imaging Agent (quantum dots) for cancer therapy and bioImaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-Imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy. From the Clinical Editor This study investigated the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles functionalized with a targeting ligand (EpCAM aptamer) and an Imaging Agent (quantum dots) for cancer therapy and bioImaging. It was concluded that the studied multifunctional targeted nanoparticle may become a viable and efficient approach in cancer therapy.
Asunción Roig - One of the best experts on this subject based on the ideXlab platform.
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supercritical fluid assisted one pot synthesis of biocompatible core γ fe2o3 shell sio2 nanoparticles as high relaxivity t2 contrast Agents for magnetic resonance Imaging
Advanced Functional Materials, 2009Co-Authors: Elena Taboada, Raul Solanas, Elisenda Rodríguez, Ralph Weissleder, Asunción RoigAbstract:Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(γ-Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol–gel chemistry and supercritical fluid technology. This one-step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T2 MRI Imaging Agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.
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Supercritical-Fluid-Assisted One-Pot Synthesis of Biocompatible Core( γ -Fe 2 O 3 )/Shell(SiO 2 ) Nanoparticles as High Relaxivity T 2 -Contrast Agents for Magnetic Resonance Imaging
Advanced Functional Materials, 2009Co-Authors: Elena Taboada, Raul Solanas, Elisenda Rodríguez, Ralph Weissleder, Asunción RoigAbstract:Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(γ-Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol–gel chemistry and supercritical fluid technology. This one-step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T2 MRI Imaging Agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.
Mei-ping Kung - One of the best experts on this subject based on the ideXlab platform.
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whole body biodistribution and radiation dosimetry of 18f fp dtbz 18f av 133 a novel vesicular monoamine transporter 2 Imaging Agent
The Journal of Nuclear Medicine, 2010Co-Authors: Yihsin Weng, Ingtsung Hsiao, Chinsong Lu, Daniel M Skovronsky, Hsiuping Chang, Mei-ping KungAbstract:Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the endocrine cells and brain. We investigated the biodistribution and radiation dosimetry of (2R,3R,11bR)-9-(3- 18 F-fluoropropoxy)-3-isobutyl-10-methoxy-2,3,4,6,7, 11 b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ( 18 F-FP-(+)-dihydrotetrabenazine [DTBZ] or 18 F -AV-1 33), a potential VMAT2 Imaging Agent showing encouraging results in humans, to facilitate its future clinical use. Methods: Nine healthy human subjects (mean age ± SD, 58.6 ± 4.2 y) were enrolled for the whole-body PET scan. Serial images were acquired for 3 h immediately after a bolus injection of 390.7 ± 22.9 MBq of 18 F-AV-133 per individual. The source organs were delineated on PET/CT images. The OLINDA/EXM application was used to determine the equivalent dose for individual organs. Results: The radiotracer did not show any noticeable adverse effects for the 9 subjects examined. The radioactivity uptake in the brain was the highest at 7.5% ± 0.6% injected dose at 10 min after injection. High absorbed doses were found in the pancreas, liver, and upper large intestine wall. The highest-dosed organ, which received 153.3 ± 23.8 μGy/MBq, was the pancreas. The effective dose equivalent and effective dose for 18 F-AV-133 were 36.5 ± 2.8 and 27.8 ± 2.5 μSv/MBq, respectively. These values are comparable to those reported for any other 18 F-labeled radiopharmaceutical. Conclusion: 18 F-AV-133 is safe, with appropriate biodistribution and radiation dosimetry for Imaging VMAT2 sites in humans.
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Clinical acceptance of a molecular Imaging Agent: a long march with [99mTc]TRODAT
Nuclear Medicine and Biology, 2007Co-Authors: Hank F. Kung, Mei-ping KungAbstract:In the past 10 years, significant progress has been made in using a technetium-99m dopamine transporter Imaging Agent, [99mTc]TRODAT, for routine clinical studies. Developing a molecular Imaging Agent from bench to the bedside is more than a simple scientific venture. Currently, Taiwan is the only place where [99mTc]TRODAT is approved for routine clinical use in the diagnosis of Parkinson's disease. The trials and tribulations of developing [99mTc]TRODAT for routine clinical use in Taiwan provide an interesting case study in how to (critics may say, how not to) develop a molecular Imaging Agent.
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characterization of optically resolved 9 fluoropropyl dihydrotetrabenazine as a potential pet Imaging Agent targeting vesicular monoamine transporters
Nuclear Medicine and Biology, 2007Co-Authors: Mei-ping Kung, Datta E. Ponde, Rajesh Goswami, Michael R Kilbourn, Hank F. KungAbstract:Abstract Labeling derivatives of dihydrotetrabenazine (DTBZ) with F-18 ( T 1/2 =110 min) instead of C-11 ( T 1/2 =20 min) would improve their utility and availability for Imaging vesicular monoamine transporters (VMAT2) in clinical settings. The successful synthesis, reported previously, of two novel 9-fluoroalkyl(±)-DTBZ ligands prompted us to study the optically resolved active ligand 9-fluoropropyl-(+)-DTBZ (FP-(+)-DTBZ), which may have more promising characteristics. The inhibition constant ( K i ) estimated for FP-(+)-DTBZ (using [ 3 H](±)-DTBZ as the labeled ligand in rat striatal homogenates) showed a lower value as compared to the racemic FP-(±)-DTBZ (0.10±0.01 vs 0.19±0.04 nM). The inactive isomer, FP-(-)-DTBZ, displayed a much lower binding affinity with a K i value >3000 nM. Biodistribution studies in mice after an iv injection of [ 18 F]FP-(+)-DTBZ exhibited a ratio of striatum (ST, target) to cerebellum (CB, background) of 4.51 at 30 min postinjection, which is a higher value than previously obtained with the racemic ligand [ 18 F]FP-(±)-DTBZ (ST/CB=2.95). Brain extraction at 30 min after the tracer injection in mice showed that >95% of the radioactivity corresponded to the parent, nonmetabolized, compound remaining in the ST, suggesting that the tracer has an excellent in vivo stability. Furthermore, localization of the tracer in the brain examined with ex vivo autoradiography displayed a typical distribution pattern consistent with VMAT2 sites. The highest labeling was observed in monoaminergic neuron regions (caudate putamen, olfactory tubercle, nucleus accumbens, substantia nigra, dorsal raphe and locus coerules). We also tested the selective labeling of this tracer at the dopamine neurons in unilateral-lesioned mice (treated with 6-hydroxydopamine). When [ 18 F]FP-(+)-DTBZ and [ 125 I]IPT (( N -(3′-iodopropen-2′-yl)-2-beta-carbomethoxy-3-beta-(4-chlorophenyl)tropane, a selective marker for dopamine transporters (DATs) in dopaminergic neurons) were simultaneously injected into lesioned mice, we observed an excellent correlation ( r =0.95) for these tracers. From these findings, we conclude that [ 18 F]FP-(+)-DTBZ is a sensitive and selective tracer for VMAT2 binding sites and it may be useful for in vivo evaluation of diseases relating to changes of monoamine neuronal integrity.
Hank F. Kung - One of the best experts on this subject based on the ideXlab platform.
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18f 2s 4s 4 3 fluoropropyl glutamine as a tumor Imaging Agent
Molecular Pharmaceutics, 2014Co-Authors: Zehui Wu, Seok Rye Choi, Genxun Li, Brian P Lieberman, Karl Ploessl, Hank F. KungAbstract:Although the growth and proliferation of most tumors is fueled by glucose, some tumors are more likely to metabolize glutamine. In particular, tumor cells with the upregulated c-Myc gene are generally reprogrammed to utilize glutamine. We have developed new 3-fluoropropyl analogs of glutamine, namely [18F](2S,4R)- and [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 3 and 4, to be used as probes for studying glutamine metabolism in these tumor cells. Optically pure isomers labeled with 18F and 19F (2S,4S) and (2S,4R)-4-(3-fluoropropyl)glutamine were synthesized via different routes and isolated in high radiochemical purity (≥95%). Cell uptake studies of both isomers showed that they were taken up efficiently by 9L tumor cells with a steady increase over a time frame of 120 min. At 120 min, their uptake was approximately two times higher than that of l-[3H]glutamine ([3H]Gln). These in vitro cell uptake studies suggested that the new probes are potential tumor Imaging Agents. Yet, the lower chemical yield of the ...
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Clinical acceptance of a molecular Imaging Agent: a long march with [99mTc]TRODAT
Nuclear Medicine and Biology, 2007Co-Authors: Hank F. Kung, Mei-ping KungAbstract:In the past 10 years, significant progress has been made in using a technetium-99m dopamine transporter Imaging Agent, [99mTc]TRODAT, for routine clinical studies. Developing a molecular Imaging Agent from bench to the bedside is more than a simple scientific venture. Currently, Taiwan is the only place where [99mTc]TRODAT is approved for routine clinical use in the diagnosis of Parkinson's disease. The trials and tribulations of developing [99mTc]TRODAT for routine clinical use in Taiwan provide an interesting case study in how to (critics may say, how not to) develop a molecular Imaging Agent.
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characterization of optically resolved 9 fluoropropyl dihydrotetrabenazine as a potential pet Imaging Agent targeting vesicular monoamine transporters
Nuclear Medicine and Biology, 2007Co-Authors: Mei-ping Kung, Datta E. Ponde, Rajesh Goswami, Michael R Kilbourn, Hank F. KungAbstract:Abstract Labeling derivatives of dihydrotetrabenazine (DTBZ) with F-18 ( T 1/2 =110 min) instead of C-11 ( T 1/2 =20 min) would improve their utility and availability for Imaging vesicular monoamine transporters (VMAT2) in clinical settings. The successful synthesis, reported previously, of two novel 9-fluoroalkyl(±)-DTBZ ligands prompted us to study the optically resolved active ligand 9-fluoropropyl-(+)-DTBZ (FP-(+)-DTBZ), which may have more promising characteristics. The inhibition constant ( K i ) estimated for FP-(+)-DTBZ (using [ 3 H](±)-DTBZ as the labeled ligand in rat striatal homogenates) showed a lower value as compared to the racemic FP-(±)-DTBZ (0.10±0.01 vs 0.19±0.04 nM). The inactive isomer, FP-(-)-DTBZ, displayed a much lower binding affinity with a K i value >3000 nM. Biodistribution studies in mice after an iv injection of [ 18 F]FP-(+)-DTBZ exhibited a ratio of striatum (ST, target) to cerebellum (CB, background) of 4.51 at 30 min postinjection, which is a higher value than previously obtained with the racemic ligand [ 18 F]FP-(±)-DTBZ (ST/CB=2.95). Brain extraction at 30 min after the tracer injection in mice showed that >95% of the radioactivity corresponded to the parent, nonmetabolized, compound remaining in the ST, suggesting that the tracer has an excellent in vivo stability. Furthermore, localization of the tracer in the brain examined with ex vivo autoradiography displayed a typical distribution pattern consistent with VMAT2 sites. The highest labeling was observed in monoaminergic neuron regions (caudate putamen, olfactory tubercle, nucleus accumbens, substantia nigra, dorsal raphe and locus coerules). We also tested the selective labeling of this tracer at the dopamine neurons in unilateral-lesioned mice (treated with 6-hydroxydopamine). When [ 18 F]FP-(+)-DTBZ and [ 125 I]IPT (( N -(3′-iodopropen-2′-yl)-2-beta-carbomethoxy-3-beta-(4-chlorophenyl)tropane, a selective marker for dopamine transporters (DATs) in dopaminergic neurons) were simultaneously injected into lesioned mice, we observed an excellent correlation ( r =0.95) for these tracers. From these findings, we conclude that [ 18 F]FP-(+)-DTBZ is a sensitive and selective tracer for VMAT2 binding sites and it may be useful for in vivo evaluation of diseases relating to changes of monoamine neuronal integrity.