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Molecular Imaging

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https://www.readbyqxmd.com/read/29098927/radiochemistry-and-preclinical-pet-imaging-of-68-ga-desferrioxamine-radiotracers-targeting-prostate-specific-membrane-antigen
#1
Eleni Gourni, Luigi Del Pozzo, Mark Bartholomä, Yvonne Kiefer, Philipp T Meyer, Helmut R Maecke, Jason P Holland
Radiotracers incorporating the urea-based Glu-NH-C(O)-NH-Lys group have gained prominence due to their role in targeting prostate-specific membrane antigen (PSMA)-a clinical biomarker of prostate cancer. Here, the synthesis, radiolabeling, and in vitro and in vivo characterization of two (68)Ga-radiolabeled Glu-NH-C(O)-NH-Lys radiotracers conjugated to the desferrioxamine B (DFO) chelate were evaluated. Two linker groups based on amide bond and thiourea coupling chemistries were employed to develop (68)Ga-DFO-Nsucc-PSMA ((68)Ga-4) and (68)Ga-DFO- pNCS-Bn-PSMA ((68)Ga-7), respectively...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29073808/whole-body-biodistribution-dosimetry-and-metabolite-correction-of-11-c-palmitate-a-pet-tracer-for-imaging-of-fatty-acid-metabolism
#2
Nana L Christensen, Steen Jakobsen, Anna C Schacht, Ole L Munk, Aage K O Alstrup, Lars P Tolbod, Hendrik J Harms, Søren Nielsen, Lars C Gormsen
INTRODUCTION: Despite the decades long use of [(11)C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were performed in 2 pigs and 2 healthy volunteers by whole-body [(11)C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29067878/brain-penetration-of-the-ros1-alk-inhibitor-lorlatinib-confirmed-by-pet
#3
T Lee Collier, Kevin P Maresca, Marc D Normandin, Paul Richardson, Timothy J McCarthy, Steven H Liang, Rikki N Waterhouse, Neil Vasdev
The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique (11)C and (18)F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. A major goal in cancer therapeutics is to measure the concentrations of this drug in the brain metastases of patients with lung cancer, and penetration of the blood-brain barrier is important for optimal therapeutic outcomes...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29037107/first-in-man-evaluation-of-124-i-pgn650-a-pet-tracer-for-detecting-phosphatidylserine-as-a-biomarker-of-the-solid-tumor-microenvironment
#4
Richard Laforest, Farrokh Dehdashti, Yongjian Liu, Jennifer Frye, Sarah Frye, Hannah Luehmann, Deborah Sultan, Joseph S Shan, Bruce D Freimark, Barry A Siegel
PURPOSE: PGN650 is a F(ab')2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with (124)I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28948859/whole-body-distribution-of-leukemia-and-functional-total-marrow-irradiation-based-on-flt-pet-and-dual-energy-ct
#5
Taiki Magome, Jerry Froelich, Shernan G Holtan, Yutaka Takahashi, Michael R Verneris, Keenan Brown, Kathryn Dusenbery, Jeffrey Wong, Susanta K Hui
This report describes a multimodal whole-body 3'-deoxy-3'[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28929924/the-search-for-a-subtype-selective-pet-imaging-agent-for-the-gabaa-receptor-complex-evaluation-of-the-radiotracer-11-c-ado-in-nonhuman-primates
#6
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA, GABAB, and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28929923/rethinking-brain-cancer-therapy-tumor-enzyme-activatable-theranostic-nanoparticles
#7
Heike E Daldrup-Link
This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28927325/molecular-imaging-of-hydrolytic-enzymes-using-pet-and-spect
#8
Brian P Rempel, Eric W Price, Christopher P Phenix
Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28893116/imaging-hepatocellular-carcinoma-with-68-ga-citrate-pet-first-clinical-experience
#9
Carina Mari Aparici, Spencer C Behr, Youngho Seo, R Kate Kelley, Carlos Corvera, Kenneth T Gao, Rahul Aggarwal, Michael J Evans
While cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging is the primary method for diagnosing hepatocellular carcinoma (HCC), they provide little biological insight into this molecularly heterogeneous disease. Nuclear imaging tools that can detect molecular subsets of tumors could greatly improve diagnosis and management of HCC. To this end, we conducted a patient study to determine whether HCC can be resolved using (68)Ga-citrate positron emission tomography (PET). One patient with recurrent HCC was injected with 300 MBq of (68)Ga-citrate and imaged with PET/CT 249 minutes post injection...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28884622/ex-vivo-and-in-vivo-noninvasive-imaging-of-epidermal-growth-factor-receptor-inhibition-on-colon-tumorigenesis-using-activatable-near-infrared-fluorescent-probes
#10
Shengli Ding, Randall E Blue, Emily Moorefield, Hong Yuan, Pauline K Lund
BACKGROUND: Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection. OBJECTIVE: To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in Apc(Min/+) mice. METHODS: The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28877656/longitudinal-evaluation-of-myocardial-fatty-acid-and-glucose-metabolism-in-fasted-and-nonfasted-spontaneously-hypertensive-rats-using-micropet-ct
#11
Jennifer S Huber, Andrew M Hernandez, Mustafa Janabi, James P O'Neil, Kathleen M Brennan, Stephanie T Murphy, Youngho Seo, Grant T Gullberg
Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog (18)F-fluoro-6-thia heptadecanoic acid ((18)F-FTHA) and glucose analog (18)F-fluorodeoxyglucose ((18)F-FDG) under normal or fasting conditions...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28877655/developing-a-strategy-for-interventional-molecular-imaging-of-oxidized-low-density-lipoprotein-in-atherosclerosis
#12
Samata S Pandey, Dorian O Haskard, Ramzi Y Khamis
The identification of vulnerable coronary artery atherosclerotic plaques offers the prospect of either localized or systematic therapeutic targeting in order to prevent myocardial infarction. Molecular imaging of atherosclerosis adds to morphological imaging by focusing on the immunobiology hidden in and behind the endothelium and therefore may be able to improve the identification of prospective culprit lesions. Our focus has been on identifying arterial accumulation of oxidized low-density lipoprotein (oxLDL) by exploiting advances in knowledge of vascular pathobiology...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28856922/detection-and-delineation-of-oral-cancer-with-a-parp1-targeted-optical-imaging-agent
#13
Susanne Kossatz, Wolfgang Weber, Thomas Reiner
More sensitive and specific methods for early detection are imperative to improve survival rates in oral cancer. However, oral cancer detection is still largely based on visual examination and histopathology of biopsy material, offering no molecular selectivity or spatial resolution. Intuitively, the addition of optical contrast could improve oral cancer detection and delineation, but so far no molecularly targeted approach has been translated. Our fluorescently labeled small-molecule inhibitor PARPi-FL binds to the DNA repair enzyme poly(ADP-ribose)polymerase 1 (PARP1) and is a potential diagnostic aid for oral cancer delineation...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28856921/near-infrared-intraoperative-imaging-can-successfully-identify-malignant-pleural-mesothelioma-after-neoadjuvant-chemotherapy
#14
Jarrod D Predina, Andrew Newton, Greg Kennedy, M Kenneth Lee, Sunil Singhal
Malignant pleural mesothelioma is a deadly disease. Complete surgical resection provides patients with the best opportunity for long-term survival. Unfortunately, identification of disease during resection can be challenging. In this report, we describe successful intraoperative utilization of the near-infrared imaging agent, indocyanine green, to help the surgeon identify malignant disease in a patient with malignant pleural mesothelioma who had previously received neoadjuvant chemotherapy. This technology may ultimately enhance the thoracic surgeon's ability to identify small disease deposits at the time of resection...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28849712/combination-of-fluorescence-guided-surgery-with-photodynamic-therapy-for-the-treatment-of-cancer
#15
Jun He, Leping Yang, Wenjun Yi, Wentao Fan, Yu Wen, Xiongying Miao, Li Xiong
Specific visualization of body parts is needed during surgery. Fluorescence-guided surgery (FGS) uses a fluorescence contrast agent for in vivo tumor imaging to detect and identify both malignant and normal tissues. There are several advantages and clinical benefits of FGS over other conventional medical imaging modalities, such as its safety, effectiveness, and suitability for real-time imaging in the operating room. Recent advancements in contrast agents and intraoperative fluorescence imaging devices have led to a greater potential for intraoperative fluorescence imaging in clinical applications...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28849698/imaging-neurotensin-receptor-in-prostate-cancer-with-64-cu-labeled-neurotensin-analogs
#16
Huaifu Deng, Hui Wang, He Zhang, Mengzhe Wang, Ben Giglio, Xiaofen Ma, Guihua Jiang, Hong Yuan, Zhanhong Wu, Zibo Li
INTRODUCTION: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. MATERIALS AND METHODS: Three (64)Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28730928/feasibility-of-na-18-f-pet-ct-and-mri-for-noninvasive-in-vivo-quantification-of-knee-pathophysiological-bone-metabolism-in-a-canine-model-of-post-traumatic-osteoarthritis
#17
Maria I Menendez, Bianca Hettlich, Lai Wei, Michael V Knopp
PURPOSE: To assess and quantify by molecular imaging knee osseous metabolic changes serially in an in vivo canine model of posttraumatic osteoarthritis (PTOA) of the knee utilizing sodium fluoride (Na(18)F) positron emission tomography (PET)/computed tomography (CT) coregistered with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sodium fluoride PET imaging of 5 canines was performed prior to anterior cruciate ligament transection (ACLT) and 2 times post-ACLT (3 and 12 weeks)...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28707500/noninvasive-imaging-of-immune-checkpoint-ligand-pd-l1-in-tumors-and-metastases-for-guiding-immunotherapy
#18
Samit Chatterjee, Wojciech G Lesniak, Sridhar Nimmagadda
Immunotherapy holds great promise in cancer treatment. The challenges in advancing immunotherapies lie in patient stratification and monitoring therapy. Noninvasive detection of immune checkpoint ligand PD-L1 can serve as an important biomarker for guidance and monitoring of immunotherapy. Here in, we provide an overview of our efforts to develop clinically translatable PD-L1-specific imaging agents for quantitative and real-time assessment of PD-L1 expression in tumor microenvironment.
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28654388/commentary-on-a-microfluidic-platform-to-design-crosslinked-hyaluronic-acid-nanoparticles-chanps-for-enhanced-mri
#19
Maria Russo, Paolo Bevilacqua, Paolo Antonio Netti, Enza Torino
Strategies to enhance the relaxometric properties of gadolinium (Gd)-based contrast agents (CAs) for magnetic resonance imaging (MRI), without the chemical modification of chelates, have recently had a strong impact on the diagnostic field. We have taken advantage of the interaction between Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and the hydrogel structure of hyaluronic acid to design cross-linked hyaluronic acid nanoparticles down to 35 nm for use in MRI applications. The proposed bioformulations enable the control of the relaxometric properties of CAs, thus boosting the relaxation rate of T1...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28654387/phosphatidylserine-targeted-nanotheranostics-for-brain-tumor-imaging-and-therapeutic-potential
#20
Lulu Wang, Amyn A Habib, Akiva Mintz, King C Li, Dawen Zhao
Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers...
January 1, 2017: Molecular Imaging
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