Recent progress in fluorine-18 labelled peptide radiopharmaceuticals

International Nuclear Information System (INIS)

Okarvi, S.M.

2001-01-01

The application of biologically active peptides labelled with positron-emitting nuclides has emerged as a useful and interesting field in nuclear medicine. Small synthetic receptor-binding peptides are currently the preferred agents over proteins and antibodies for diagnostic imaging of various tumours. Due to the smaller size of peptides, both higher target-to-background ratios and rapid blood clearance can often be achieved with radiolabelled peptides. Hence, short-lived positron emission tomography (PET) isotopes are potential candidates for labelling peptides. Among a number of positron-emitting nuclides, fluorine-18 appears to be the best candidate for labelling bioactive peptides by virtue of its favourable physical and nuclear characteristics. The major disadvantage of labelling peptides with 18 F is the laborious and time-consuming preparation of the 18 F labelling agents. In recent years, various techniques have been developed which allow efficient labelling of peptides with 18 F without affecting their receptor-binding properties. Moreover, the development of a variety of prosthetic groups has facilitated the efficient and site-specific labelling of peptides with 18 F. The 18 F-labelled peptides hold enormous clinical potential owing to their ability to quantitatively detect and characterise a wide variety of human diseases when using PET. Recently, a number of 18 F-labelled bioactive peptides have shown great promise as diagnostic imaging agents. This review presents the recent developments in 18 F-labelled biologically active peptides used in PET. (orig.)

Fluorine-18 labeled tracers for PET studies in the neurosciences

Energy Technology Data Exchange (ETDEWEB)

Ding, Yu-Shin; Fowler, J.S.

1995-12-31

This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.

Fluorine-18 labeled tracers for PET studies in the neurosciences

International Nuclear Information System (INIS)

Ding, Yu-Shin; Fowler, J.S.

1995-01-01

This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments

F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET

Energy Technology Data Exchange (ETDEWEB)

Wu, Anna M. [Univ. of California, Los Angeles, CA (United States)

2013-01-18

The goal of the proposed work is to develop novel dual-labeled molecular imaging probes for multimodality imaging. Based on small, engineered antibodies called diabodies, these probes will be radioactively tagged with Fluorine-18 for PET imaging, and fused to luciferases for optical (bioluminescence) detection. Performance will be evaluated and validated using a prototype integrated optical-PET imaging system, OPET. Multimodality probes for optical-PET imaging will be based on diabodies that are dually labeled with 18F for PET detection and fused to luciferases for optical imaging. 1) Two sets of fusion proteins will be built, targeting the cell surface markers CEA or HER2. Coelenterazine-based luciferases and variant forms will be evaluated in combination with native substrate and analogs, in order to obtain two distinct probes recognizing different targets with different spectral signatures. 2) Diabody-luciferase fusion proteins will be labeled with 18F using amine reactive [18F]-SFB produced using a novel microwave-assisted, one-pot method. 3) Sitespecific, chemoselective radiolabeling methods will be devised, to reduce the chance that radiolabeling will inactivate either the target-binding properties or the bioluminescence properties of the diabody-luciferase fusion proteins. 4) Combined optical and PET imaging of these dual modality probes will be evaluated and validated in vitro and in vivo using a prototype integrated optical-PET imaging system, OPET. Each imaging modality has its strengths and weaknesses. Development and use of dual modality probes allows optical imaging to benefit from the localization and quantitation offered by the PET mode, and enhances the PET imaging by enabling simultaneous detection of more than one probe.

Radiolabeling of liposomes and polymeric micelles with PET-isotopes

Energy Technology Data Exchange (ETDEWEB)

Ingemann Jensen, A.T.

2013-06-01

glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were prepared. [18F]Radiofluorination of these substrates was performed on fully automated equipment using a classic Kryptofix222-mediated procedure in DMSO. Yields were poor, 3-17% depending on conditions. The [18F]fluorinated probes were purified in-situ on SEP-Paks. The cholesteryl ether mesylate performed best. This substrate was radiolabeled and formulated in long-circulating liposomes by drying the probe and the lipids together, followed by hydration by magnetic stirring. The liposomes were extruded through 100 nm filter on fully automated equipment. Animal studies were done in tumor-bearing mice, and PET-scans were performed over 8 hours. Clear tumor uptake, as well as hepatic and splenic uptake, was observed, corresponding to expected liposomal pharmacokinetics. Tumor uptake was quantifiable (tumor-tomuscle ratio at 8 h: 2.20), showing that the maximum scan duration with 18F is sufficient for visualizing tumor tissue. Because of the low [18F]radiofluorination yields obtained, we investigated ways of labeling lipophilic substrates in nonpolar solvents. This involved the transfer of [18]HF gas from a solution of concentrated sulphuric acid into a receiving vial containing the substrate in toluene. A phosphazene base was present to bind [18]HF and mediate fluorination. This procedure made it possible to fluorinate highly lipophilic substrates in 71% yields. Chapter 3. Radiolabeling of polymeric micelles with 64Cu (18% positron decay, T = 12.7 h) was investigated. 64Cu allows longer scans (up to 48 hours), which mirrors the duration of nanoparticle pharmacokinetics. It is a metal and must be attached to polymeric micelles by covalently conjugated chelators. DOTA and CB-TE2A are two such chelators, but DOTA is widely believed to be unstable in-vivo. DOTA and CB-TE2A were conjugated to triblock polymeric micelles in the shellregion. Here, they were

Radiolabeling of liposomes and polymeric micelles with PET-isotopes

International Nuclear Information System (INIS)

Ingemann Jensen, A.T.

2013-01-01

glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were prepared. [18F]Radiofluorination of these substrates was performed on fully automated equipment using a classic Kryptofix222-mediated procedure in DMSO. Yields were poor, 3-17% depending on conditions. The [18F]fluorinated probes were purified in-situ on SEP-Paks. The cholesteryl ether mesylate performed best. This substrate was radiolabeled and formulated in long-circulating liposomes by drying the probe and the lipids together, followed by hydration by magnetic stirring. The liposomes were extruded through 100 nm filter on fully automated equipment. Animal studies were done in tumor-bearing mice, and PET-scans were performed over 8 hours. Clear tumor uptake, as well as hepatic and splenic uptake, was observed, corresponding to expected liposomal pharmacokinetics. Tumor uptake was quantifiable (tumor-tomuscle ratio at 8 h: 2.20), showing that the maximum scan duration with 18F is sufficient for visualizing tumor tissue. Because of the low [18F]radiofluorination yields obtained, we investigated ways of labeling lipophilic substrates in nonpolar solvents. This involved the transfer of [18]HF gas from a solution of concentrated sulphuric acid into a receiving vial containing the substrate in toluene. A phosphazene base was present to bind [18]HF and mediate fluorination. This procedure made it possible to fluorinate highly lipophilic substrates in 71% yields. Chapter 3. Radiolabeling of polymeric micelles with 64Cu (18% positron decay, T = 12.7 h) was investigated. 64Cu allows longer scans (up to 48 hours), which mirrors the duration of nanoparticle pharmacokinetics. It is a metal and must be attached to polymeric micelles by covalently conjugated chelators. DOTA and CB-TE2A are two such chelators, but DOTA is widely believed to be unstable in-vivo. DOTA and CB-TE2A were conjugated to triblock polymeric micelles in the shellregion. Here, they were

Expedited Synthesis of Fluorine-18 Labeled Phenols. A Missing Link in PET Radiochemistry

Energy Technology Data Exchange (ETDEWEB)

Katzenellenbogen, John A. [Univ. of Illinois, Champaign, IL (United States); Zhou, Dong [Washington Univ., St. Louis, MO (United States)

2015-03-26

Fluorine-18 (F-18) is arguably the most valuable radionuclide for positron emission tomographic (PET) imaging. However, while there are many methods for labeling small molecules with F-18 at aliphatic positions and on electron-deficient aromatic rings, there are essentially no reliable and practical methods to label electron-rich aromatic rings such as phenols, with F-18 at high specific activity. This is disappointing because fluorine-labeled phenols are found in many drugs; there are also many interesting plant metabolites and hormones that contain either phenols or other electron-rich aromatic systems such as indoles whose metabolism, transport, and distribution would be interesting to study if they could readily be labeled with F-18. Most approaches to label phenols with F-18 involve the labeling of electron-poor precursor arenes by nucleophilic aromatic substitution, followed by subsequent conversion to phenols by oxidation or other multi-step sequences that are often inefficient and time consuming. Thus, the lack of good methods for labeling phenols and other electron-rich aromatics with F-18 at high specific activity represents a significant methodological gap in F-18 radiochemistry that can be considered a “Missing Link in PET Radiochemistry”. The objective of this research project was to develop and optimize a series of unusual synthetic transformations that will enable phenols (and other electron-rich aromatic systems) to be labeled with F-18 at high specific activity, rapidly, reliably, and conveniently, thereby bridging this gap. Through the studies conducted with support of this project, we have substantially advanced synthetic methodology for the preparation of fluorophenols. Our progress is presented in detail in the sections below, and much has been published or presented publication; other components are being prepared for publication. In essence, we have developed a completely new method to prepare o-fluorophenols from non-aromatic precursors

Fluorinated tracers for imaging cancer with positron emission tomography

International Nuclear Information System (INIS)

Couturier, Olivier; Chatal, Jean-Francois; Luxen, Andre; Vuillez, Jean-Philippe; Rigo, Pierre; Hustinx, Roland

2004-01-01

2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images. Further, the 110-min physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site and imaging protocols that may span hours, which permits dynamic studies and assessment of potentially fairly slow metabolic processes. The synthesis of fluorinated tracers as an alternative to FDG was initially tested using nucleophilic fluorination of the molecule, as performed when radiolabelling with iodine-124 or bromide-76. However, in addition to being long, with multiple steps, this procedure is not recommended for bioactive molecules containing reactive groups such as amine or thiol groups. Radiochemical yields are also often low. More recently, radiosynthesis from prosthetic group precursors, which allows easier radiolabelling of biomolecules, has led to the development of numerous fluorinated tracers. Given the wide availability of 18 F, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated radiotracers recently developed and under investigation for possible PET imaging in cancer patients. Two groups can be distinguished. The first includes ''generalist'' tracers, i.e. tracers amenable to use in a wide variety of tumours and indications, very similar in this respect to FDG. These are tracers for non-specific cell metabolism, such as protein synthesis, amino acid transport, nucleic acid synthesis or membrane component synthesis. The second group consists of ''specific'' tracers for receptor expression (i.e. oestrogens or somatostatin), cell

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

International Nuclear Information System (INIS)

Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

2007-01-01

Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

Fluorine-18-labelled molecules: synthesis and application in medical imaging

International Nuclear Information System (INIS)

Dolle, F.; Perrio, C.; Barre, L.; Lasne, M.C.; Le Bars, D.

2006-01-01

Positron emission tomography (PET) is one of the more powerful available techniques for medical imaging. It relies on the use of molecules labelled with a positron emitter (β + ). Among those emitters, fluorine-18, available from a cyclotron, is a radionuclide of choice because of its relatively long-half-life (109.8 min) and the relatively low energy of the emitted-positron. The electrophilic form of fluorine-18 ([ 18 F]F 2 or reagents derived from [ 18 F]F 2 ) is mainly used for hydrogen or metal substitutions on aromatic or vinylic carbons. The presence of the stable isotope (fluorine-19) in the radiotracers limits their use in medical imaging. The nucleophilic form of fluorine-18 (alkaline mono-fluoride, K[ 18 F]F, the most used), obtained from irradiation of enriched water, is widely used in aliphatic and (hetero)aromatic substitutions for the synthesis of radiotracers with high specific radioactivity. Some examples of radio-fluorinated tracers used in PET are presented, as well as some of their in vivo applications in human. (authors)

Fluorine-18 radiopharmaceuticals beyond [F-18]FDG for use in oncology and neurosciences

NARCIS (Netherlands)

Coenen, H. H.; Elsinga, P. H.; Iwata, R.; Kilbourn, M. R.; Pillai, M. R. A.; Rajan, M. G. R.; Wagner, H. N.; Zaknun, J. J.

2010-01-01

Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 (F-18) tracers that can be used for PET studies

Comparison between whole-body MRI and Fluorine-18-Fluorodeoxyglucose PET or PET/CT in oncology: a systematic review

International Nuclear Information System (INIS)

Ciliberto, Mario; Maggi, Fabio; Treglia, Giorgio; Padovano, Federico; Calandriello, Lucio; Giordano, Alessandro; Bonomo, Lorenzo

2013-01-01

The aim of the article is to systematically review published data about the comparison between positron emission tomography (PET) or PET/computed tomography (PET/CT) using Fluorine-18-Fluorodeoxyglucose (FDG) and whole-body magnetic resonance imaging (WB-MRI) in patients with different tumours. A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through April 2012 and regarding the comparison between FDG-PET or PET/CT and WB-MRI in patients with various tumours was carried out. Forty-four articles comprising 2287 patients were retrieved in full-text version, included and discussed in this systematic review. Several articles evaluated mixed tumours with both diagnostic methods. Concerning the specific tumour types, more evidence exists for lymphomas, bone tumours, head and neck tumours and lung tumours, whereas there is less evidence for other tumour types. Overall, based on the literature findings, WB-MRI seems to be a valid alternative method compared to PET/CT in oncology. Further larger prospective studies and in particular cost-effectiveness analysis comparing these two whole-body imaging techniques are needed to better assess the role of WB-MRI compared to FDG-PET or PET/CT in specific tumour types

Al18F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging

Science.gov (United States)

Cleeren, Frederik; Lecina, Joan; Ahamed, Muneer; Raes, Geert; Devoogdt, Nick; Caveliers, Vicky; McQuade, Paul; Rubins, Daniel J; Li, Wenping; Verbruggen, Alfons; Xavier, Catarina; Bormans, Guy

2017-01-01

Positron emission tomography (PET) using radiolabeled biomolecules is a translational molecular imaging technology that is increasingly used in support of drug development. Current methods for radiolabeling biomolecules with fluorine-18 are laborious and require multistep procedures with moderate labeling yields. The Al18F-labeling strategy involves chelation in aqueous medium of aluminum mono[18F]fluoride ({Al18F}2+) by a suitable chelator conjugated to a biomolecule. However, the need for elevated temperatures (100-120 °C) required for the chelation reaction limits its widespread use. Therefore, we designed a new restrained complexing agent (RESCA) for application of the AlF strategy at room temperature. Methods. The new chelator RESCA was conjugated to three relevant biologicals and the constructs were labeled with {Al18F}2+ to evaluate the generic applicability of the one-step Al18F-RESCA-method. Results. We successfully labeled human serum albumin with excellent radiochemical yields in less than 30 minutes and confirmed in vivo stability of the Al18F-labeled protein in rats. In addition, we efficiently labeled nanobodies targeting the Kupffer cell marker CRIg, and performed µPET studies in healthy and CRIg deficient mice to demonstrate that the proposed radiolabeling method does not affect the functional integrity of the protein. Finally, an affibody targeting HER2 (PEP04314) was labeled site-specifically, and the distribution profile of (±)-[18F]AlF(RESCA)-PEP04314 in a rhesus monkey was compared with that of [18F]AlF(NOTA)-PEP04314 using whole-body PET/CT. Conclusion. This generic radiolabeling method has the potential to be a kit-based fluorine-18 labeling strategy, and could have a large impact on PET radiochemical space, potentially enabling the development of many new fluorine-18 labeled protein-based radiotracers. PMID:28824726

Al18F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging.

Science.gov (United States)

Cleeren, Frederik; Lecina, Joan; Ahamed, Muneer; Raes, Geert; Devoogdt, Nick; Caveliers, Vicky; McQuade, Paul; Rubins, Daniel J; Li, Wenping; Verbruggen, Alfons; Xavier, Catarina; Bormans, Guy

2017-01-01

Positron emission tomography (PET) using radiolabeled biomolecules is a translational molecular imaging technology that is increasingly used in support of drug development. Current methods for radiolabeling biomolecules with fluorine-18 are laborious and require multistep procedures with moderate labeling yields. The Al 18 F-labeling strategy involves chelation in aqueous medium of aluminum mono[ 18 F]fluoride ({Al 18 F} 2+ ) by a suitable chelator conjugated to a biomolecule. However, the need for elevated temperatures (100-120 °C) required for the chelation reaction limits its widespread use. Therefore, we designed a new restrained complexing agent (RESCA) for application of the AlF strategy at room temperature. Methods. The new chelator RESCA was conjugated to three relevant biologicals and the constructs were labeled with {Al 18 F} 2+ to evaluate the generic applicability of the one-step Al 18 F-RESCA-method. Results. We successfully labeled human serum albumin with excellent radiochemical yields in less than 30 minutes and confirmed in vivo stability of the Al 18 F-labeled protein in rats. In addition, we efficiently labeled nanobodies targeting the Kupffer cell marker CRIg, and performed µPET studies in healthy and CRIg deficient mice to demonstrate that the proposed radiolabeling method does not affect the functional integrity of the protein. Finally, an affibody targeting HER2 (PEP04314) was labeled site-specifically, and the distribution profile of (±)-[ 18 F]AlF(RESCA)-PEP04314 in a rhesus monkey was compared with that of [ 18 F]AlF(NOTA)-PEP04314 using whole-body PET/CT. Conclusion. This generic radiolabeling method has the potential to be a kit-based fluorine-18 labeling strategy, and could have a large impact on PET radiochemical space, potentially enabling the development of many new fluorine-18 labeled protein-based radiotracers.

General method for labeling siRNA by click chemistry with fluorine-18 for the purpose of PET imaging.

Science.gov (United States)

Mercier, Frédéric; Paris, Jérôme; Kaisin, Geoffroy; Thonon, David; Flagothier, Jessica; Teller, Nathalie; Lemaire, Christian; Luxen, André

2011-01-19

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction, was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An alkyne solid support CPG for the preparation of monostranded oligonucleotides functionalized with alkyne has been developed. Two complementary azide labeling agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3-[(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical yields (decay-corrected), respectively. After annealing with the complementary strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and purity.

A novel method of 18F radiolabeling for PET.

NARCIS (Netherlands)

McBride, W.J.; Sharkey, R.M.; Karacay, H.; D'Souza, C.A.; Rossi, E.A.; Laverman, P.; Chang, C.H.; Boerman, O.C.; Goldenberg, D.M.

2009-01-01

Small biomolecules are typically radiolabeled with (18)F by binding it to a carbon atom, a process that usually is designed uniquely for each new molecule and requires several steps and hours to produce. We report a facile method wherein (18)F is first attached to aluminum as Al(18)F, which is then

Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [18F]F-PHNO

International Nuclear Information System (INIS)

Vasdev, Neil; Seeman, Philip; Garcia, Armando; Stableford, Winston T.; Nobrega, Jose N.; Houle, Sylvain; Wilson, Alan A.

2007-01-01

Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([ 11 C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [ 3 H]domperidone in homogenates of rat striatum and inhibition of binding to [ 3 H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [ 3 H]domperidone and [ 3 H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K i High , was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K i High =2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [ 18 F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the promising in vitro pharmacological profile, [ 18

Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [{sup 18}F]F-PHNO

Energy Technology Data Exchange (ETDEWEB)

Vasdev, Neil [PET Centre for Addiction and Mental Health, Toronto, Ontario, Canada, M5T-1R8 (Canada) and Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)]. E-mail: neil.vasdev@camhpet.ca; Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Garcia, Armando [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Stableford, Winston T. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Nobrega, Jose N. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Houle, Sylvain [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Wilson, Alan A. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)

2007-02-15

Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [{sup 3}H]domperidone in homogenates of rat striatum and inhibition of binding to [{sup 3}H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [{sup 3}H]domperidone and [{sup 3}H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K {sub i} {sup High}, was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K {sub i} {sup High}=2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [{sup 18}F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the

Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

Science.gov (United States)

Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

2017-10-01

Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

Fluorinated tropinyl esters for application with PET

International Nuclear Information System (INIS)

Emran, A.M.; Cherif, A.; Yang, D.J.; Flynn, D.D.

1993-01-01

Regulation of muscarinic acetylcholine receptors (MAR) number and function occurs with various exogenous chemicals and pathological conditions. Use of positron emission tomography (PET) has potential in investigating MAR in living humans. This requires synthesis of appropriate radiolabelled tracers with high affinity and high specific activity. Several analogs of atropine and tropacocaine, including fluorinated derivatives, were synthesized and evaluated for their MAR binding affinity. Specific structural alterations correlated with changes in receptor affinity. Substitution was directed primarily on aromatic rings of the acid moieties. In vitro binding assays demonstrated that molecular substitution on some of the compounds retained significant affinity for MAR. Changing the acid moiety on these molecules resulted in a change in MAR affinity. Substitution o the aromatic ring of the acid moiety was also associated with change in receptor affinity. Preliminary radiofluorination has been successful. These compounds provide new tools to study MAR dynamics in the living human brain

SiRNAs in vivo imaging: methodology of fluorine-18 radiolabelling and application for the optimization of the siRNAs biodistribution and pharmaceutical properties

International Nuclear Information System (INIS)

Viel, Th.

2008-01-01

As RNA interference is a natural process which enables eukaryote cells to regulate the gene expressions, to control transposons, and to struggle against some viruses, two imagery techniques have been used in this research, i.e. optical imagery and Positron Emission Tomography (PET) imagery, to study the various modifications of the small interferential RNAs (siRNA). Different chemically modified siRNAs have been prepared and their in vitro activity, their in vivo metabolism (by HPLC analysis), their bio-distribution and their pharmacokinetic properties (by PET imagery) after marking them with fluorine-18. Their in vivo activity has been assessed by optical imagery

Fluorine-18-labeling of polymerized nano-micelles for in vivo PET imaging

International Nuclear Information System (INIS)

Kuhnast, B.; Hinnen, F.; Mackiewicz, N.; Tavitian, B.; Duconge, F.; Dolle, F.; Gravel, E.; Doris, E.

2011-01-01

Complete text of publication follows: Objectives: One of the key issues in nano-medicine, and in particular in the field of cancer treatment and follow up, is the development of nano-particles able to improve the delivery of drugs or contrast agents. It is well established that passive targeting by nano-particles is favoured by specific features of tumors, a phenomena usually defined as the enhanced permeability and retention (EPR) effect. While several nano-particulate systems in the 70- 200 nm size range have been explored for cancer targeting by the EPR effect (liposomes, dendrimers, ceramic or metallic nano-particles, carbon nano-tubes...), recent studies suggested that particles of smaller sizes (≤ 30 nm) might better diffuse through blood vessel walls and reach deeper tumor tissues. Recently, a novel series of small-sized (diameter of ca. 10 nm) and highly stable (polymerized) micelles were designed as drug nano-carriers. For in vivo 3D-imaging purposes, these micelles were provided with a sulfhydryl function permitting prosthetic conjugation with maleimide-based reagents such as AlexaFluor680 R (AF680) for optical fluorescence imaging and [ 18 F]FPyME (1-[3-(2-[ 18 F]fluoropyridin-3-yloxy)propyl]pyrrole-2, 5-dione), a prosthetic reagent labeled with the positron-emitter fluorine-18 for PET imaging, which latter work is presented herein. Methods: nano-micelles were synthesized using standard already reported procedures and comprise a defined molar ratio of functionalized diacetylene-containing poly(ethyleneglycol) (PEG-2000) lipids (pentacosa-10, 12- diyn-1-oxy-penta-tetraconta-ethylene-glycols). Preparation includes polymerization of the diacetylene functions borne by the C-25 lipophilic chains upon UV-irradiation at 254 nm via a topochemical 1, 4-addition mechanism. [ 18 F]FPyME was conjugated with the micelles in a 1/9 (v:v) mixture (1 mL) of DMSO and 0.1 M aq. PBS (pH 7.5) at room temperature for 15 min. The conjugated micelles were then separated from

Synthesis and pharmacological evaluation of a new series of radiolabeled ligands for 5-HT7 receptor PET neuroimaging

International Nuclear Information System (INIS)

Colomb, Julie; Becker, Guillaume; Forcellini, Elsa; Meyer, Sandra; Buisson, Lauriane; Zimmer, Luc; Billard, Thierry

2014-01-01

Introduction: The brain serotonin-7 receptor (5-HT 7 ) is the most recently discovered serotonin receptor. It is targeted by several drug-candidates in psychopharmacology and neuropharmacology. In these fields, positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the development process from preclinical discovery to clinical phases. We recently described fluorinated 5-HT 7 radioligands, inspired by the structure of SB269970, the prototypical 5-HT 7 antagonist. Although these results were promising, it appeared that the radiotracer-candidates suffered, among other drawbacks, from too low a 5-HT 7 receptor affinity. Methods: In the present study, seven structural analogs of SB269970 were synthesized using design strategies aiming to improve their radiopharmacological properties. Their 5-HT 7 binding properties were investigated by cellular functional assay. The nitro-precursors of the analogs were radiolabeled by [ 18 F-]nucleophilic substitution, and in vitro autoradiography was performed in rat brain, followed by in vivo microPET. Result: The chemical and radiochemical purity of the fluorine radiotracers was > 99% with specific activity in the 40–129 GBq/μmol range. The seven derivatives presented heterogeneous binding affinities toward 5-HT 7 and 5-HT 1A receptors. While [ 18 F]2F3P3 had promising characteristics in vitro, it showed poor brain penetration in vivo, partially reversed after pharmacological inhibition of P-glycoprotein. Conclusions: These results indicated that, while chemical modification of these series improved several radiotracer-candidates in terms of 5-HT 7 receptor affinity and specificity toward 5-HT 1A receptors, other physicochemical modulations would be required in order to increase brain penetration

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis

Energy Technology Data Exchange (ETDEWEB)

Bassetti, Matteo; Merelli, Maria; Della Siega, Paola; Righi, Elda [Santa Maria della Misericordia University Hospital, Infectious Diseases Division, Udine (Italy); Di Gregorio, Fernando [Santa Maria della Misericordia University Hospital, Microbiology Unit, Udine (Italy); Screm, Maria; Scarparo, Claudio [Santa Maria della Misericordia University Hospital, Radiology Unit, Udine (Italy)

2017-06-15

Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases. Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012. Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up. Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation. (orig.)

Synthesis of geminal difluorides by oxidative desulfurization-difluorination of alkyl aryl thioethers with halonium electrophiles in the presence of fluorinating reagents and its application for 18F-radiolabeling.

Science.gov (United States)

Hugenberg, Verena; Wagner, Stefan; Kopka, Klaus; Schober, Otmar; Schäfers, Michael; Haufe, Günter

2010-09-17

Various ω-substituted 1,1-difluoroalkanes are synthesized in good yields from alkyl aryl thioethers by a new oxidative desulfurization-difluorination protocol with the reagents combination of 1,3-dibromo-5,5-dimethylhydantoin (DBH) as an oxidizer and pyridine·9HF (Py·9HF) as a fluoride source. The reaction proceeds via a fluoro-Pummerer-type rearrangement followed by an oxidative desulfurization-fluorination step. Starting from α-fluorinated thioethers, this reaction is promising for (18)F-labeling (τ(1/2) = 110 min) of ligands applicable for positron emission tomography (PET). Using the combination of DBH and carrier-added Py·9H[(18)F]F, an (18)F-labeled difluoride was synthesized from the corresponding α-fluoro thioether with a radiochemical yield of 9%.

Cyclotron-produced radioisotopes and their clinical use at the Austin PET Centre

International Nuclear Information System (INIS)

Tochon-Danguy, H.J.

1997-01-01

A Centre for Positron Emission Tomography (PET) has been established within the Department of Nuclear Medicine at the Austin and Repatriation Medical Centre in Melbourne. PET is a non-invasive technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic equipment consists of a medical cyclotron (10 MeV proton and 5 MeV deuteron), six lead-shielded hot cells with associated radiochemistry facilities and a whole body PET scanner. During its first five years of operation, the Melbourne PET Centre, has pursued a strong radiolabelling development program, leading to an ambitious clinical program in neurology, oncology and cardiology. This presentation will describe the basic principles of the PET technique and review the cyclotron-produced radioisotopes and radiopharmaceuticals. Radiolabelling development programs and clinical applications are also addressed

Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging

International Nuclear Information System (INIS)

Evens, Nele; Muccioli, Giulio G.; Houbrechts, Nele; Lambert, Didier M.; Verbruggen, Alfons M.; Van Laere, Koen; Bormans, Guy M.

2009-01-01

Introduction: The type 2 cannabinoid (CB 2 ) receptor is part of the endocannabinoid system and has been suggested as a mediator of several central and peripheral inflammatory processes. Imaging of the CB 2 receptor has been unsuccessful so far. We synthesized and evaluated a carbon-11- and a fluorine-18-labeled 2-oxoquinoline derivative as new PET tracers with high specificity and affinity for the CB 2 receptor. Methods: Two 2-oxoquinoline derivatives were synthesized and radiolabeled with either carbon-11 or fluorine-18. Their affinity and selectivity for the human CB 2 receptor were determined. Biological evaluation was done by biodistribution, radiometabolite and autoradiography studies in mice. Results: In vitro studies showed that both compounds are high affinity CB 2 -specific inverse agonists. Biodistribution study of the tracers in mice showed a high in vivo initial brain uptake and fast brain washout, in accordance with the low CB 2 receptor expression levels in normal brain. A persistently high in vivo binding to the spleen was observed, which was inhibited by pretreatment with two structurally unrelated CB 2 selective inverse agonists. In vitro autoradiography studies with the radioligands confirmed CB 2 -specific binding to the mouse spleen. Conclusion: We synthesized two novel CB 2 receptor PET tracers that show high affinity/selectivity for CB 2 receptors. Both tracers show favourable characteristics as radioligands for central and peripheral in vivo visualization of the CB 2 receptor and are promising candidates for primate and human CB 2 PET imaging.

Development of fluorine 18 labelled MPPF, radiopharmaceutical tracer for serotoninergic system exploration

International Nuclear Information System (INIS)

Le Bars, D.; Tochon-Danguy, H.

2002-01-01

Full text: Positron Emission Tomography (PET) is a non-invasive method for exploration, in man and animals, of metabolism with radiopharmaceutical tracers labelled with positron emitters such as carbon 11 and fluorine 18 obtained with a cyclotron. Among the ever increasing number of tracers focussed at the CNS neurotransmission, the discovery of a new family of serotoninergic 5HT 1A antagonists (WAY 100635) has led to the first in vivo imaging of 5HT 1A receptors in man, located in cerebral structures such as cortex and hippocampus. Exploration of serotonine parthway is particulaly interesting in normal or diseased state, as this neurotransmitter is involved in the control of mood, sleep and is probably altered in psychiatric disorders. CERMEP, in collaboration with other PET centres has developped a new 5HT 1A antagonist, MPPF, labelled with fluorine 18. [ 18 F]MPPF has the advantadge of fluorine 18 labelling, with a longer half-life (110 min vs 20 min for carbon 11) and easier radiosynthesis automation. Moreover, MPPF affinity for 5HT 1A is close to serotonin itself, thus enabling displacement of MPPF by endogenous serotonin during pharmacological challenges. Automated radiosynthesis of MPPF is achieved via a classical [ 18 F]F - fluoro for nitro displacement, activated by a catalyst, on a nitro precursor prepared in four steps. A final HPLC purification ensures the production of [ 18 F]MPPF with a high purity and a high specific activity. Ex vivo autoradiographies and PET studies in animals (rat, cat) have shown the excellent specificity of MPPF for the 5HT 1A receptor. Experiments with intracerebral β probe have evidenced the displacement of [ 18 F]MPPF by endogenous serotonin after fenfluramine injection. [ 18 F]MPPF is now used in man for non-invasive PET studies of serotoninergic system. Normal volunteers matched for age and sex have been screened as a database and to compute a mathematical model of the tracer kinetic describing 5HT 1A receptor affinity and

Synthesis of 6-[18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET

International Nuclear Information System (INIS)

Damont, A.; Boisgard, R.; Kuhnast, B.; Lemee, F.; Raggiri, G.; Tavitian, B.; Dolle, F.; Boisgard, R.; Tavitian, B.; Scarf, A.M.; Scarf, A.M.; Kassiou, M.; Da Pozzo, E.; Martini, C.; Selleri, S.; Kassiou, M.; Tavitian, B.; Kassiou, M.

2011-01-01

6-Fluoro-PBR28 (N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide), a fluorinated analogue of the recently developed TSPO 18 kDa ligand PBR28, was synthesized and labelled with fluorine- 18. 6-Fluoro-PBR28 and its 6-chloro/6-bromo counterparts were synthesized in six chemical steps and obtained in 16%, 10% and 19% overall yields, respectively. Labelling with fluorine-18 was performed in one single step (chlorine/bromine-for-fluorine heteroaromatic substitution) using a Zymate-XP robotic system affording HPLC-purified, ready-to-inject, 6-[ 18 F]fluoro-PBR28 (≥95% radiochemically pure). Non decay-corrected overall yields were 9-10% and specific radioactivities ranged from 74 to 148 GBq/μmol. In vitro binding experiments, dynamic μPET studies performed in a rat model of acute neuro-inflammation (unilaterally, AMPA-induced, striatum-lesioned rats) and ex vivo autoradiography on the same model demonstrated the potential of 6-[ 18 F]fluoro-PBR28 to image the TSPO 18 kDa using PET. (authors)

Cyclotron-produced radioisotopes and their clinical use at the Austin PET Centre

Energy Technology Data Exchange (ETDEWEB)

Tochon-Danguy, H.J. [Centre for PET, Melbourne, VIC (Australia). Austin and Repatriation Medical Centre

1997-12-31

A Centre for Positron Emission Tomography (PET) has been established within the Department of Nuclear Medicine at the Austin and Repatriation Medical Centre in Melbourne. PET is a non-invasive technique based on the use of biologically relevant compounds labelled with short-lived positron-emitting radionuclides such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18. The basic equipment consists of a medical cyclotron (10 MeV proton and 5 MeV deuteron), six lead-shielded hot cells with associated radiochemistry facilities and a whole body PET scanner. During its first five years of operation, the Melbourne PET Centre, has pursued a strong radiolabelling development program, leading to an ambitious clinical program in neurology, oncology and cardiology. This presentation will describe the basic principles of the PET technique and review the cyclotron-produced radioisotopes and radiopharmaceuticals. Radiolabelling development programs and clinical applications are also addressed. 30 refs., 1 tab., 1 fig.

Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351

International Nuclear Information System (INIS)

Harada, Ryuichi; Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu; Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka; Okamura, Nobuyuki

2016-01-01

18 F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of 18 F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of 18 F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of 18 F-THK5351. The isolated radiometabolite of 18 F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

Synthesis, radiofluorination, and preliminary evaluation of the potential 5-HT2A receptor agonists [18 F]Cimbi-92 and [18 F]Cimbi-150

DEFF Research Database (Denmark)

Edgar, Fraser Graeme; Hansen, Hanne D; Leth-Petersen, Sebastian

2017-01-01

An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F-labelled ......An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F......-labelled agonist 5-HT2A receptor (5-HT2A R) tracer is highly sought after. Herein, we report a 2-step, 1-pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5-HT2A R. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled...

Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

Energy Technology Data Exchange (ETDEWEB)

Vanasschen, Christian; Brandt, Marie; Ermert, Johannes [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany); Neumaier, Bernd [Institute for Radiochemistry and Experimental Molecular Imaging, Medical Clinics, University of Cologne (Germany); Coenen, Heinz H [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany)

2015-05-18

The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

International Nuclear Information System (INIS)

Vanasschen, Christian; Brandt, Marie; Ermert, Johannes; Neumaier, Bernd; Coenen, Heinz H

2015-01-01

The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands.

Science.gov (United States)

Taylor, Nicholas J; Emer, Enrico; Preshlock, Sean; Schedler, Michael; Tredwell, Matthew; Verhoog, Stefan; Mercier, Joel; Genicot, Christophe; Gouverneur, Véronique

2017-06-21

Molecules labeled with fluorine-18 ( 18 F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18 F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18 F-fluorination of aryl boron reagents with 18 F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18 F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

Fluorinated ceramide trafficking inhibitors as Alzheimer's disease radiomarkers

International Nuclear Information System (INIS)

Ferko, B.; Berkes, D.; Crivelli, S. M.

2017-01-01

Herein, we describe the synthesis of the most potent analogues of HPA-12 radiolabeled with fluorine-18 from the universal precursor m-Br-HPA-12. The enantioselective access to this precursor is based on a practical and reliable crystallization induced asymmetric transformation (CIAT) of 3- Bromo-benzoylacrylic acid and suitable chiral auxiliary. Incorporation of alkynol chains was accomplished by Sonogashira coupling, followed by triple bond reduction and protection of primary hydroxyl group delivering the intermediates for the radiofluorinated analogues of HPA-12. Radiofluorination of analogues of HPA-12 and PET imaging was carried out by our partners at University of Maastricht. (authors)

Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma

DEFF Research Database (Denmark)

Mylam, Karen Juul; Nielsen, Anne Lerberg; Pedersen, Lars Møller

2014-01-01

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially curable type of lymphoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is part of clinical routine for DLBCL in most hospitals and also recommended for staging and end-of-therapy evaluation. FDG......-PET/computed tomography (CT) is able to identify nodal and extranodal sites with greater accuracy than CT alone. Little evidence supports the use of surveillance FDG-PET imaging in the follow-up setting because of high rates of false-positive scans and because most studies are retrospective. This article discusses FDG...

Use of fluorine-18-BPA PET images and image registration to enhance radiation treatment planning for boron neutron capture therapy

Science.gov (United States)

Khan, Mohammad Khurram

The Monte-Carlo based simulation environment for radiation therapy (SERA) software is used to simulate the dose administered to a patient undergoing boron neutron capture therapy (BNCT). Point sampling of tumor tissue results in an estimate of a uniform boron concentration scaling factor of 3.5. Under conventional treatment protocols, this factor is used to scale the boron component of the dose linearly and homogenously within the tumor and target volumes. The average dose to the tumor cells by such a method could be improved by better methods of quantifying the in-vivo 10B biodistribution. A better method includes radiolabeling para-Boronophenylalanine (p-BPA) with 18F and imaging the pharmaceutical using positron emission tomography (PET). This biodistribution of 18F-BPA can then be used to better predict the average dose delivered to the tumor regions. This work uses registered 18F-BPA PET images to incorporate the in-vivo boron biodistribution within current treatment planning. The registered 18F-BPA PET images are then coupled in a new computer software, PET2MRI.m, to linearly scale the boron component of the dose. A qualititative and quantitative assessment of the dose contours is presented using the two approaches. Tumor volume, tumor axial extent, and target locations are compared between using MRI or PET images to define the tumor volume. In addition, peak-to-normal brain value at tumor axial center is determined for pre and post surgery patients using 18F-BPA PET images. The differences noted between the registered GBM tumor volumes (range: 34.04--136.36%), tumor axial extent (range: 20--150%), and the beam target location (1.27--4.29 cm) are significantly different. The peak-to-normal brain values are also determined at the tumor axial center using the 18F-BPA PET images. The peak-to-normal brain values using the last frame of the pre-surgery study for the GBM patients ranged from 2.05--3.4. For post surgery time weighted PET data, the peak

Synthesis of positron labeled photoactive compounds: 18F labeled aryl azides for positron labeling of biochemical molecules

International Nuclear Information System (INIS)

Hashizume, Kazunari; Hashimoto, Naota; Miyake, Yoshihiro

1995-01-01

The authors have prepared various [ 18 F] fluorine labeled aryl azides as a novel photoactive compounds suitable for positron labeling of biochemical molecules. The introduction of fluorine substituents to aryl azides can be expected to have dramatic effects on their nature and reactivity toward photolysis. Positron labeled reagents for labeling proteins or peptides have recently attracted considerable attention due to their wide applicability in biochemistry and positron emission tomography (PET). Various labeled azide compounds are often used in biochemistry for radiolabeling biological molecules by photolysis, but there have been no reports on the preparation or use of fluorine-18 labeled azides. The authors now report a novel synthesis of 18 F-labeled aryl azides which will have wide application in the biochemistry and nuclear medicine as a means for 18 F-fluorine labeling for proteins, peptides, and nucleic acids. 2 tabs

Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

Energy Technology Data Exchange (ETDEWEB)

Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

2016-11-15

{sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

An Unusual Case of Anaphylaxis After Fluorine-18-Labeled Fluorodeoxyglucose Injection

Energy Technology Data Exchange (ETDEWEB)

Lee, Dong Yun; Lee, Jong Jin; Kwon, Hyouksoo; Moon, Woo Yeon; Jin, Soyoung; Lee, Sang Ju; Oh, Seung Jun; Ryu, Jin Sook [Univ. of Ulsan College of Medicine, Ulsan (Korea, Republic of)

2013-09-15

[{sup 18}F]FDG (fluorine-18 fluoro-2-deoxy-D-glucose) positron emission tomography (PET) is used worldwide for oncologic and neurologic applications. To date, the potential harm caused by [{sup 18}F]FDG has focused on its radiation exposure effects rather than on its pharmacological effects. While an allergic response in the form of a skin manifestation has been reported after exposure to [{sup 18}F]FDG, this report describes the first case of hypotension following exposure to this tracer. Here, the development of anaphylaxis after [{sup 18}F]FDG injection is described.

Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors

International Nuclear Information System (INIS)

Slobbe, Paul; Windhorst, Albert D.; Walsum, Marijke Stigter-van; Schuit, Robert C.; Smit, Egbert F.; Niessen, Heiko G.; Solca, Flavio; Stehle, Gerd; Dongen, Guus A.M.S. van; Poot, Alex J.

2014-01-01

Introduction: Afatinib is an irreversible ErbB family blocker that was approved for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron emission tomography (PET) with fluorine-18 labeled afatinib provides a means to obtain improved understanding of afatinib tumor disposition in vivo. PET imaging with [ 18 F]afatinib may also provide a method to select treatment responsive patients. The aim of this study was to label afatinib with fluorine-18 and evaluate its potential as TKI-PET tracer in tumor bearing mice. Methods: A radiochemically novel coupling, using peptide coupling reagent BOP, was explored and optimized to synthesize [ 18 F]afatinib, followed by a metabolite analysis and biodistribution studies in two clinically relevant lung cancer cell lines, xenografted in nude mice. Results: A reliable [ 18 F]afatinib radiosynthesis was developed and the tracer could be produced in yields of 17.0 ± 2.5% calculated from [ 18 F]F − and >98% purity. The identity of the product was confirmed by co-injection on HPLC with non-labeled afatinib. Metabolite analysis revealed a moderate rate of metabolism, with >80% intact tracer in plasma at 45 min p.i. Biodistribution studies revealed rapid tumor accumulation and good retention for a period of at least 2 hours, while background tissues showed rapid clearance of the tracer. Conclusion: We have developed a method to synthesize [ 18 F]afatinib and related fluorine-18 labeled 4-anilinoquinazolines. [ 18 F]Afatinib showed good stability in vivo, justifying further evaluation as a TKI-PET tracer

[{sup 18}F]FDG-PET in large vessel vasculitis; [{sup 18}F]FDG-PET bei Grossgefaess-Vaskulitiden

Energy Technology Data Exchange (ETDEWEB)

Hauser, A.S.D.; Walter, M.A. [Universitaetsspital Basel (Switzerland). Inst. fuer Nuklearmedizin

2007-06-15

[{sup 18}F]FDG-PET is a non-invasive metabolic imaging modality based on the regional distribution of fluorine-18-fluorodeoxyglucose that is highly effective in assessing the activity and the extent of giant cell arteritis and Takayasu's arteritis. It has shown to identify more affected vascular regions than morphologic imaging with Magnetic Resonance Imaging in both diseases. A visual grading of vascular [{sup 18}F]FDG-uptake helps to discriminate arteritis from atherosclerosis und therefore provides high specificity. High sensitivity is reached by scanning during the active inflammatory phase. [{sup 18}F]FDG-PET has the potential to develop into a valuable tool in the diagnostic work-up of giant cell arteritis and Takayasu's arteritis, respectively, and might become a first-line investigation technique. Therefore consensus regarding the most favorable imaging procedure as well as further clinical evidence is needed. The purpose of this review is to summarize current information on the present clinical data and to assist nuclear medicine practitioners in recommending, performing and interpreting the results of [{sup 18}F]FDG-PET in patients with suspected large vessel vasculitis. (orig.)

6-[Fluorine-18]Fluorodopamine pharmacokinetics and dosimetry in humans

International Nuclear Information System (INIS)

Goldstein, D.S.; Coronado, L.; Kopin, I.J.

1994-01-01

PET scanning after injection of 6-[ 18 F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[ 18 F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[ 18 F]fluorodopamine into 10 normal volunteers. The main target organs for 6-[ 18 F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [ 18 F]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. At administered doses required to visualize the left ventricular myocardium in humans, a 6-[ 18 F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. 22 refs., 2 figs., 5 tabs

Imaging dopamine-2 receptors in cebus apella at PET with F-18 fluoropropylspiperone and F-18 fluorinated benzamide neuroleptic

International Nuclear Information System (INIS)

Mukherjee, J.; Yasillo, N.J.; Luh, K.E.; Diamond, M.; Levy, D.; Chen, C.T.; Cooper, M.

1990-01-01

Tardive dyskinesia (TD), an intractable disorder believed to involve dysfunction of dopamine D-2 receptors, often occurs with neuroleptic treatment in neuropsychiatric illness. This paper investigates the role of these receptors using a unique primate model of TD with newly developed (F-18) fluorinated radioligands. Two radioligands, (F-18)FPMB (one of a new class of fluorinated benzamide neuroleptics) have been used to image these receptors in a normal Cebus apella. Either (F-18)FPSP or (F-18)FPMB was administered intravenously to a normal Cebus, which was scanned for 2 hours in a PETT VI tomograph

Dibenzodiazepines (clozapine) and analogues were labelled with carrier-free carbon-11 and fluorine-18

International Nuclear Information System (INIS)

Bender, D.

1993-12-01

Pharmacologically active dibenzodiazepines were labelled with carbon-11 and fluorine-18, in particular the atypical neuroleptic clozapine (8-Cl-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e]-[1,4]-diazepine) for pharmakokinetic studies with positron emission tomography (PET). (orig./EF)

PET radiochemistry: synthesis of 2-[18 F]-fluorine-2-deoxy-D-glucose

International Nuclear Information System (INIS)

Lopez D, F.A.; Flores M, A.; Zarate M, A.; Romo, E.

2005-01-01

The present work describes the method for the synthesis of the 2-[ 18 F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

Diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography in gallbladder cancer: A meta-analysis.

Science.gov (United States)

Annunziata, Salvatore; Pizzuto, Daniele Antonio; Caldarella, Carmelo; Galiandro, Federica; Sadeghi, Ramin; Treglia, Giorgio

2015-10-28

To meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the evaluation of primary tumor in patients with gallbladder cancer (GBCa). A comprehensive literature search of studies published through 30(th) June 2014 regarding the role of (18)F-FDG PET and PET/CT in the evaluation of primary gallbladder cancer (GBCa) was performed. All retrieved studies were reviewed. Pooled sensitivity and specificity of (18)F-FDG PET or PET/CT in the evaluation of primary GBCa were calculated. The area under the summary receiving operator characteristics curve (AUC) was calculated to measure the accuracy of these methods. Sub-analyses considering the device used (PET vs PET/CT) were carried out. Twenty-one studies comprising 495 patients who underwent (18)F-FDG PET or PET/CT for suspicious GBCa were selected for the systematic review. The meta-analysis of 13 selected studies provided the following results: sensitivity 87% (95%CI: 82%-92%), specificity 78% (95%CI: 68%-86%). The AUC was 0.88. Improvement of sensitivity and specificity was observed when PET/CT was used. (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of primary tumor in GBCa patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. PET/CT seems to have a better diagnostic accuracy than PET alone in this setting.

[18F]FDG-PET in large vessel vasculitis

International Nuclear Information System (INIS)

Hauser, A.S.D.; Walter, M.A.

2007-01-01

[ 18 F]FDG-PET is a non-invasive metabolic imaging modality based on the regional distribution of fluorine-18-fluorodeoxyglucose that is highly effective in assessing the activity and the extent of giant cell arteritis and Takayasu's arteritis. It has shown to identify more affected vascular regions than morphologic imaging with Magnetic Resonance Imaging in both diseases. A visual grading of vascular [ 18 F]FDG-uptake helps to discriminate arteritis from atherosclerosis und therefore provides high specificity. High sensitivity is reached by scanning during the active inflammatory phase. [ 18 F]FDG-PET has the potential to develop into a valuable tool in the diagnostic work-up of giant cell arteritis and Takayasu's arteritis, respectively, and might become a first-line investigation technique. Therefore consensus regarding the most favorable imaging procedure as well as further clinical evidence is needed. The purpose of this review is to summarize current information on the present clinical data and to assist nuclear medicine practitioners in recommending, performing and interpreting the results of [ 18 F]FDG-PET in patients with suspected large vessel vasculitis. (orig.)

Microfluidic radiolabeling of biomolecules with PET radiometals

International Nuclear Information System (INIS)

Zeng Dexing; Desai, Amit V.; Ranganathan, David; Wheeler, Tobias D.; Kenis, Paul J.A.; Reichert, David E.

2013-01-01

Introduction: A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. Methods: The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64 Cu and 68 Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Results: Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64 Cu/ 68 Ga using the microreactor, which demonstrates the ability to label both small and large molecules. Conclusions: A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.

Nuclear medicine. In vivo PET-TDM or PET diagnosis with fluorine 18 and other positron emitters - FR 6

International Nuclear Information System (INIS)

Herain, C.; Machacek, C.; Menechal, P.; Aubert, B.; Celier, D.; Rehel, J.L.; Vidal, J.P.; Barbe, R.; Lahaye, T.; Gauron, C.; Barret, C.; Biau, A.; Donnarieix, D.; Gambini, D.; Gondran, C.; Guerin, C.; Marande, J.L.; Mercier, J.; Paycha, F.; Pierrat, N.

2012-03-01

This sheet first indicates the different personnel categories concerned with application of various legal arrangements associated with the practice of in vivo diagnosis by positron emission tomography (PET) coupled or not with tomodensitometry (PDM) using fluorine 18 or other positron emitters. It briefly describes the procedures, indicates the hazards and risks associated with the use of sealed sources and X ray generators or of unsealed sources, describes how the risk is assessed, how controlled and surveyed areas are determined, how the personnel is classified according to workstation studies, and how the dose control method is selected with respect to each personnel category. It describes how a risk management strategy is defined and implemented (risk reduction, technical measures for the installation, protection measures, education and training, prevention action, how to deal with incidents and dysfunction). It describes the various aspects and practices of medical survey for the personnel, in case of pregnancy, and by using a medical file and performing a post-professional follow-up, and by taking on anomalies and incidents. It also describes how risk management is to be assessed, and mentions some other risks. An example of workstation study is provided in appendix

Aliphatic Nucleophilic Radio-fluorination

International Nuclear Information System (INIS)

Roeda, D.; Dolle, F.

2010-01-01

In this review we are looking at some aspects of nucleophilic aliphatic radio-fluorination, notably the labelled fluoride source, design aspects, the leaving group and the solvent. It should be clear that there is more to this branch of radiolabelling than one would suspect from the frequently used standard tosylate replacement with kryptofix/[ 18 F]fluoride in acetonitrile or DMSO. Competitive elimination can be a serious problem that can affect both yield and purification. De-protection of sensitive groups after radiolabelling and its possible side reactions can complicate purification. The right choice of leaving group and protecting groups may be crucial. Newer developments such as the use of tertiary alcohols or ionic liquids as solvents, long-chain poly-fluorinated sulphonate leaving groups facilitating fluorous solid phase extraction, or immobilisation of the precursor on a solid phase support may help to solve these problems, for example the longstanding problems with [ 18 F]FLT, whereas older concepts such as certain cyclic reactive entities for ring opening or even an abandoned reagent as [ 18 F]DAST should not be forgotten. (authors)

Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

Directory of Open Access Journals (Sweden)

Vadim Bernard-Gauthier

2015-12-01

Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

Diagnostic Performance of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Postchemotherapy Management of Patients with Seminoma: Systematic Review and Meta-Analysis

OpenAIRE

Giorgio Treglia; Ramin Sadeghi; Salvatore Annunziata; Carmelo Caldarella; Francesco Bertagna; Luca Giovanella

2014-01-01

Objective. To meta-analyze published data about the diagnostic performance of fluorine-18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the postchemotherapy management of patients with seminoma. Methods. A comprehensive literature search of studies published through January 2014 on this topic was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity and specificity, positive and negative predicti...

Reference values for fluorine-18-fluorodeoxyglucose and fluorine-18-sodium fluoride uptake in human arteries

DEFF Research Database (Denmark)

Blomberg, Björn A; Thomassen, Anders; de Jong, Pim A

2017-01-01

OBJECTIVE: Reference values of fluorine-18-fluorodeoxyglucose (F-FDG) and fluorine-18-sodium fluoride (F-NaF) uptake in human arteries are unknown. The aim of this study was to determine age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. PARTICIPANTS AND METHODS...

Microfluidic radiolabeling of biomolecules with PET radiometals.

Science.gov (United States)

Zeng, Dexing; Desai, Amit V; Ranganathan, David; Wheeler, Tobias D; Kenis, Paul J A; Reichert, David E

2013-01-01

A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both ⁶⁴Cu and ⁶⁸Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with ⁶⁴Cu/⁶⁸Ga using the microreactor, which demonstrates the ability to label both small and large molecules. A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions. Copyright © 2013 Elsevier Inc. All rights reserved.

A first-in-man PET study of [18F]PSS232, a fluorinated ABP688 derivative for imaging metabotropic glutamate receptor subtype 5.

Science.gov (United States)

Warnock, Geoffrey; Sommerauer, Michael; Mu, Linjing; Pla Gonzalez, Gloria; Geistlich, Susanne; Treyer, Valerie; Schibli, Roger; Buck, Alfred; Krämer, Stefanie D; Ametamey, Simon M

2018-06-01

Non-invasive imaging of metabotropic glutamate receptor 5 (mGlu 5 ) in the brain using PET is of interest in e.g., anxiety, depression, and Parkinson's disease. Widespread application of the most widely used mGlu 5 tracer, [ 11 C]ABP688, is limited by the short physical half-life of carbon-11. [ 18 F]PSS232 is a fluorinated analog with promising preclinical properties and high selectivity and specificity for mGlu 5 . In this first-in-man study, we evaluated the brain uptake pattern and kinetics of [ 18 F]PSS232 in healthy volunteers. [ 18 F]PSS232 PET was performed with ten healthy male volunteers aged 20-40 years. Seven of the subjects received a bolus injection and the remainder a bolus/infusion protocol. Cerebral blood flow was determined in seven subjects using [ 15 O]water PET. Arterial blood activity was measured using an online blood counter. Tracer kinetics were evaluated by compartment modeling and parametric maps were generated for both tracers. At 90 min post-injection, 59.2 ± 11.1% of total radioactivity in plasma corresponded to intact tracer. The regional first pass extraction fraction of [ 18 F]PSS232 ranged from 0.41 ± 0.06 to 0.55 ± 0.03 and brain distribution pattern matched that of [ 11 C]ABP688. Uptake kinetics followed a simple two-tissue compartment model. The volume of distribution of total tracer (V T , ml/cm 3 ) ranged from 1.18 ± 0.20 for white matter to 2.91 ± 0.51 for putamen. The respective mean distribution volume ratios (DVR) with cerebellum as the reference tissue were 0.88 ± 0.06 and 2.12 ± 0.10, respectively. The tissue/cerebellum ratios of a bolus/infusion protocol (30/70 dose ratio) were close to the DVR values. Brain uptake of [ 18 F]PSS232 matched the distribution of mGlu 5 and followed a two-tissue compartment model. The well-defined kinetics and the possibility to use reference tissue models, obviating the need for arterial blood sampling, make [ 18 F]PSS232 a promising fluorine-18 labeled

Fluorine-18 labelled compounds

International Nuclear Information System (INIS)

Kleijn, J.P. de

1978-01-01

The work presented in this thesis deals with the problems involved in the adaption of reactor-produced fluorine-18 to the synthesis of 18 F-labelled organic fluorine compounds. Several 18 F-labelling reagents were prepared and successfully applied. The limitations to the synthetic possibilities of reactor-produced fluoride- 18 become manifest in the last part of the thesis. An application to the synthesis of labelled aliphatic fluoro amino acids has appeared to be unsuccessful as yet, although some other synthetic approaches can be indicated. Seven journal articles (for which see the availability note) are used to compose the four chapters and three appendices. The connecting text gives a survey of known 18 F-compounds and methods for preparing such compounds. (Auth.)

PET Imaging of Macrophage Mannose Receptor-Expressing Macrophages in Tumor Stroma Using 18F-Radiolabeled Camelid Single-Domain Antibody Fragments.

Science.gov (United States)

Blykers, Anneleen; Schoonooghe, Steve; Xavier, Catarina; D'hoe, Kevin; Laoui, Damya; D'Huyvetter, Matthias; Vaneycken, Ilse; Cleeren, Frederik; Bormans, Guy; Heemskerk, Johannes; Raes, Geert; De Baetselier, Patrick; Lahoutte, Tony; Devoogdt, Nick; Van Ginderachter, Jo A; Caveliers, Vicky

2015-08-01

Tumor-associated macrophages constitute a major component of the stroma of solid tumors, encompassing distinct subpopulations with different characteristics and functions. We aimed to identify M2-oriented tumor-supporting macrophages within the tumor microenvironment as indicators of cancer progression and prognosis, using PET imaging. This can be realized by designing (18)F-labeled camelid single-domain antibody fragments (sdAbs) specifically targeting the macrophage mannose receptor (MMR), which has been identified as an important biomarker on this cell population. Cross-reactive anti-MMR sdAbs were generated after immunization of an alpaca with the extracellular domains of both human and mouse MMR. The lead binder was chosen on the basis of comparisons of binding affinity and in vivo pharmacokinetics. The PET tracer (18)F-fluorobenzoate (FB)-anti-MMR sdAb was developed using the prosthetic group N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), and its biodistribution, tumor-targeting potential, and specificity in terms of macrophage and MMR targeting were evaluated in mouse tumor models. Four sdAbs were selected after affinity screening, but only 2 were found to be cross-reactive for human and mouse MMR. The lead anti-MMR 3.49 sdAb, bearing an affinity of 12 and 1.8 nM for mouse and human MMR, respectively, was chosen for its favorable in vivo biodistribution profile and tumor-targeting capacity. (18)F-FB-anti-MMR 3.49 sdAb was synthesized with a 5%-10% radiochemical yield using an automated and optimized protocol. In vivo biodistribution analyses showed fast clearance via the kidneys and retention in MMR-expressing organs and tumor. The kidney retention of the fluorinated sdAb was 20-fold lower than a (99m)Tc-labeled counterpart. Compared with MMR- and C-C chemokine receptor 2-deficient mice, significantly higher uptake was observed in tumors grown in wild-type mice, demonstrating the specificity of the (18)F tracer for MMR and macrophages, respectively. Anti

Preparation of the metabotropic glutamate receptor 5 (mGluR5) PET tracer [18F]FPEB for human use: An automated radiosynthesis and a novel one-pot synthesis of its radiolabeling precursor

International Nuclear Information System (INIS)

Lim, Keunpoong; Labaree, David; Li, Songye; Huang, Yiyun

2014-01-01

The radiotracer 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile, or [ 18 F]FPEB, is a promising PET imaging agent for the metabotropic glutamate subtype 5 receptor (mGluR5). In an effort to develop a routine production method of this radiotracer for use in clinical research we adapted its radiosynthesis to an automated chemistry module. In the meanwhile, we also developed a simplified “one-pot” method for the preparation of the nitrobenzonitrile radiolabeling precursor for [ 18 F]FPEB and its reference standard to replace the existing multi-step synthetic approach. - Highlights: • Radiosynthesis of [ 18 F]FPEB was performed in a Tracerlab FX-FN automated module. • The radiolabeling precursor was prepared from a “one-pot” Suzuki coupling method. • Total synthesis time from EOB to a final injectable dose was about 90 min. • The procedure was applied in the routine preparation of [ 18 F]FPEB for human use

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

International Nuclear Information System (INIS)

Mejia, A.A.; Nakamura, T.; Masatoshi, I.; Hatazawa, J.; Masaki, M.; Watanuki, S.

1991-01-01

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, 'S' value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical

Fluorine-18 labeling of proteins

International Nuclear Information System (INIS)

Kilbourn, M.R.; Dence, C.S.; Welch, M.J.; Mathias, C.J.

1987-01-01

Two fluorine-18-labeled reagents, methyl 3-[ 18 F]fluoro-5-nitrobenzimidate and 4-[ 18 F]fluorophenacyl bromide, have been prepared for covalent attachment of fluorine-18 to proteins. Both reagents can be prepared in moderate yields (30-50%, EOB) in synthesis times of 50-70 min. Reaction of these reagents with proteins (human serum albumin, human fibrinogen, and human immunoglobulin A) is pH independent, protein concentration dependent, and takes 5-60 min at mild pH (8.0) and temperature (25-37 degrees C), in yields up to 95% (corrected). The 18 F-labeled proteins are purified by size exclusion chromatography

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma

OpenAIRE

Hall, D. O.; Hooper, C. E.; Searle, J.; Darby, M.; White, P.; Harvey, J. E.; Braybrooke, J. P.; Maskell, N. A.; Masani, V.; Lyburn, I. D.

2018-01-01

Purpose\\ud \\ud The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma.\\ud \\ud Patients and methods\\ud \\ud 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two...

Biodistribution and PET imaging of [18F]-fluoroadenosine derivatives

International Nuclear Information System (INIS)

Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

2007-01-01

Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[ 18 F]fluoro-1-β-D-arabinofuranosyl-adenine ([ 18 F]-FAA) and 3'-deoxy-3'-[ 18 F]fluoro-1-β-D-xylofuranosyl-adenine ([ 18 F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [ 18 F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [ 18 F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [ 18 F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [ 18 F]FAA in spleen and visualization of tumors, and high uptake of [ 18 F]FXA in the heart. Conclusion: These results suggest that [ 18 F]FAA may be useful for tumor imaging, while [ 18 F]FXA may have potential as a heart imaging agent with PET

Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT)

International Nuclear Information System (INIS)

Hirakawa, Tomoko; Okumura, Yoshihiro; Kato, Jun

2012-01-01

The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT). Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard. In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT. The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results. (author)

Fluorine-18 radiopharmaceuticals beyond [18F]FDG for use in oncology and neurosciences

International Nuclear Information System (INIS)

Coenen, H.H.; Elsinga, P.H.; Iwata, R.; Kilbourn, M.R.; Pillai, M.R.A.; Rajan, M.G.R.; Wagner, H.N.; Zaknun, J.J.

2010-01-01

Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ( 18 F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the 18 F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful 18 F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of 18 F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of 18 F-tracers for oncology and neurosciences. A selection of three groups of 18 F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on 'Development of 18 F radiopharmaceuticals (beyond [ 18 F]FDG) for use in oncology and neurosciences' in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more 18 F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

Efficient synthesis of a fluorine-18 labeled biotin derivative

International Nuclear Information System (INIS)

Claesener, Michael; Breyholz, Hans-Jörg; Hermann, Sven; Faust, Andreas; Wagner, Stefan; Schober, Otmar; Schäfers, Michael; Kopka, Klaus

2012-01-01

Introduction: The natural occurring vitamin biotin, also known as vitamin H or vitamin B 7 , plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10 -15 M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [ 18 F]4 for a potential application in positron emission tomography (PET). Methods: Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [ 18 F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Results: Compound [ 18 F]4 was obtained from precursor compound 3 with an average specific activity of 16 GBq/μmol within 45 min and a radiochemical yield of 45 ± 5% (decay corrected). [ 18 F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [ 18 F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. Conclusion: An efficient synthesis for [ 18 F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [ 18 F]4.

Impact of Endoscopic Ultrasonography on (18)F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment

NARCIS (Netherlands)

Hulshoff, J. B.; Mul, V. E. M.; de Boer, H. E. M.; Noordzij, W.; Korteweg, T.; van Dullemen, H. M.; Nagengast, W. B.; Oppedijk, V.; Pierie, J. P. E. N.; Plukker, John Th. M.

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Science.gov (United States)

Blake, Glen M; Puri, Tanuj; Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac

2018-02-01

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([ 18 F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [ 18 F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [ 18 F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [ 18 F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

Science.gov (United States)

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

Rare case of isolated splenic metastases from gastric cancer detected with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Kamaleshwaran, Koramadai Karuppusamy; Shibu, Deepu; Sugunan Shinto, Ajit; Sivanesan, Balasubramanian

2013-01-01

We report a rare case of isolated splenic metastasis from gastric cancer detected with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT). A 55-year-old man with gastric cancer 1 year post surgery, evaluated with PET/CT showed focal, intense uptake in the spleen, with no other abnormal findings. On splenectomy, the lesion was confirmed as metastasis from gastric cancer pathologically. (author)

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

International Nuclear Information System (INIS)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N.; Karges, Wolfram; Pauls, Sandra; Verburg, Frederik A.; Dralle, Henning; Neumaier, Bernd; Mottaghy, Felix M.

2010-01-01

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18 F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. 18 F-DOPA PET, CT and 18 F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18 F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. 18 F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18 F-DOPA PET or CT alone. (orig.)

Fluorine-18 labelling using [18F]FPyME of a small-glyco drug for potential applications in oncology

International Nuclear Information System (INIS)

Kuhnast, B.; Boisgard, R.; Hinnen, F.; Tavitian, B.; Dolle, F.; El Hadri, A.; Richard, S.; Caravano, A.; Petitou, M.

2011-01-01

Complete text of publication follows: Objectives: Proteoglycans, among which heparan sulfates (HS), are involved in many of the physiopathological steps of tumour development. Through their interaction with target proteins which regulate cell proliferation, migration, adhesion and invasion, HS play a crucial role in tumour angiogenesis and metastasis. Fully synthetic HS-mimetic oligosaccharides, also called small-glyco drugs, can be prepared and their affinity and inhibition profiles can be finely tuned according to the chemical substitutions. Access to these small-glyco drugs labeled with a positron emitter would be highly valuable in PET imaging not only for their pharmacological evaluation in vivo but also for a better understanding of tumour development. Prosthetic labeling is an efficient and reliable methodology that gives access to radiolabeled biological macromolecules. It consists in the preparation of a low molecular weight reagent bearing the radioactive isotope followed by its conjugation with the desired macromolecule. This strategy is particularly convenient when fluorine-18 is considered. Numerous prosthetic reagents have been designed among which [ 18 F]FPyME (a fluoro-pyridine-based maleimide reagent) for a selective conjugation with sulfhydryl functions borne by the macromolecules. In the present contribution, fluorine-18 labeling of the small-glyco drug EP80043 (c-2) via prosthetic labeling with [ 18 F]FPyME of the corresponding sulphated octa-saccharide, functionalized with a sulfhydryl function (2), is reported. Methods: [ 18 F]FPyME was prepared using a three-step radiochemical pathway, HPLC-purified and freed from HPLC solvents as already reported. The target octa-saccharide 2 was first synthesized as its acetylated derivative 1 to avoid intermolecular disulfide bridge formation. Prior to conjugation with [ 18 F]FPyME, 1 mg of 1 dissolved in PBS (0.1 M, pH 7.5, 100 μL) was treated with a 50 mM solution of hydroxylamine in PBS (100 μL) for

Synthesis of a fluorine-18 labeled hypoxic cell sensitizer

International Nuclear Information System (INIS)

Jerabek, P.A.; Dischino, D.D.; Kilbourn, M.R.; Welch, M.J.

1984-01-01

The objective of this work was to synthesize a positron emitting radiosensitizing agent as a potential in vivo marker of hypoxic regions within tumors, and ischemic areas of the heart and brain. The method involved radiochemical synthesis of fluorine-18 labeled 1-(2-nitro-imidazolyl)-3-fluoro-2-propanol via nucleophilic ring opening of 1-(2,3-epoxypropyl)2-nitro-imidzole by fluorine-18 labeled tetrabutylammonium fluoride (TBAF). Fluroine-18 TBAF was prepared by the exchange reaction of TBAF with aqueous flourine-18 produced by proton bombardment of enriched oxygen-18 water. The aqueous solution was evaporated carefully by azeotropic distillation with acetonitrile. The fluorine-18 labeled TBAF was taken up in N,N-dimethylacetamide or dimethysulfoxide, then reacted with the episode at 60C for 30 minutes. Separation and identification of the fluorine-18 labeled products by high performance liquid chromatography showed a radioactive peak with a retention time identical to that of 1-(2-nitro-1-imidazolyl)-3-fluoro-2-propanol and a second radioactive peak with a retention time three minutes longer in addition to unreacted fluorine-18 labeled TBAF. The second radioactive peak may represent fluorine-18 labeled 1-2-nitro-1-imidazolyl)-2-fluoro-3-propanol. The average radiochemical yield from reactions run in N,N-dimethylacetamide using 20 micromoles of TBAF and 1-2 mg of the epoxide was l7% in a synthesis time of about 40 minutes. The synthesis of fluorohydrins by the reaction of fluorine-18 labeled TBAF on epoxides represents a new method for the preparation of fluorine-18 labeled fluorohydrins

Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

International Nuclear Information System (INIS)

Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M.

1997-01-01

Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient's body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t, 1/2 =2min), nitrogen-13 (t 1/2 = 10 min), carbon-11 (t 1/2 =20 min) and fluorine-18 (t 1/2 = 110 min). These radiopharmaceuticals include [ 15 O]oxygen, [ 15 O]carbon monoxide, [ 15 O]carbon dioxide, [ 15 O]water, [ 13 N]ammonia, [ 11 C]flumazenil, [ 11 C]SCH23390, [ 18 F]fluoromisonidazole and [ 18 F]fluoro-deoxy-glucose ([ 18 F]FDG). In addition, since the half life of [ 18 F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [ 18 F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [ 18 F]thymidine analog to measure cell proliferation and a [ 11 C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors)

Fluorine 18 in tritium generator ceramic materials

International Nuclear Information System (INIS)

Jimenez-Becerril, J.; Bosch, P.; Bulbulian, S.

1992-01-01

At present time, the ceramic materials generators of tritium are very interesting mainly by the necessity of to found an adequate product for its application as fusion reactor shielding. The important element that must contain the ceramic material is the lithium and especially the isotope with mass=6. The tritium in these materials is generated by neutron irradiation, however, when the ceramic material contains oxygen, then is generated too fluorine 18 by the action of energetic atoms of tritium in recoil on the 16 O, as it is showed in the next reactions: 1) 6 Li (n, α) 3 H ; 2) 16 O( 3 H, n) 18 F . In the present work was studied the LiAlO 2 and the Li 2 O. The first was prepared in the laboratory and the second was used such as it is commercially expended. In particular the interest of this work is to study the chemical behavior of fluorine-18, since if it would be mixed with tritium it could be contaminate the fusion reactor fuel. The ceramic materials were irradiated with neutrons and also the chemical form of fluorine-18 produced was studied. It was determined the amount of fluorine-18 liberated by the irradiated materials when they were submitted to extraction with helium currents and argon-hydrogen mixtures and also it was investigated the possibility about the fluorine-18 was volatilized then it was mixed so with the tritium. Finally it was founded that the liberated amount of fluorine-18 depends widely of the experimental conditions, such as the temperature and the hydrogen amount in the mixture of dragging gas. (Author)

Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

Science.gov (United States)

Oakes, Terrence Rayford

1995-01-01

Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

[18F]FE@SNAP—A new PET tracer for the melanin concentrating hormone receptor 1 (MCHR1): Microfluidic and vessel-based approaches

Science.gov (United States)

Philippe, Cécile; Ungersboeck, Johanna; Schirmer, Eva; Zdravkovic, Milica; Nics, Lukas; Zeilinger, Markus; Shanab, Karem; Lanzenberger, Rupert; Karanikas, Georgios; Spreitzer, Helmut; Viernstein, Helmut; Mitterhauser, Markus; Wadsak, Wolfgang

2012-01-01

Changes in the expression of the melanin concentrating hormone receptor 1 (MCHR1) are involved in a variety of pathologies, especially obesity and anxiety disorders. To monitor these pathologies in-vivo positron emission tomography (PET) is a suitable method. After the successful radiosynthesis of [11C]SNAP-7941—the first PET-Tracer for the MCHR1, we aimed to synthesize its [18F]fluoroethylated analogue: [18F]FE@SNAP. Therefore, microfluidic and vessel-based approaches were tested. [18F]fluoroethylation was conducted via various [18F]fluoroalkylated synthons and direct [18F]fluorination. Only the direct [18F]fluorination of a tosylated precursor using a flow-through microreactor was successful, affording [18F]FE@SNAP in 44.3 ± 2.6%. PMID:22921745

18F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F-labelling and an in-vitro assessment of its binding with NeutravidinTM-trastuzumab pre-treated cells

International Nuclear Information System (INIS)

Smith, Tim A.D.; Simpson, Michael; Cheyne, Richard; Trembleau, Laurent

2011-01-01

In terms of nuclear decay 18 F is the most ideal PET nuclide but its short t 1/2 precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin TM -biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin TM -conjugated antibodies. Methods: Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with 18 F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin TM -conjugated trastuzumab, washed, and then incubated with 18 F-PEG-biotin. Results: The 18 F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel 18 F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin TM -conjugated trastuzumab. Conclusion: Biotin can be functionalised with boroaryl and readily 18 F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin TM -antibody conjugates. - Highlights: → Boroaryl-biotin precursor is prepared. → Rapid 18 F-fluorination is demonstrated. → HER-2 expressing breast cancer cells pre-treated with trastuzumab-Neutravidin TM . → 18 F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression.

PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

Energy Technology Data Exchange (ETDEWEB)

Giovacchini, Giampiero; Giovannini, Elisabetta; Leoncini, Rossella; Riondato, Mattia; Ciarmiello, Andrea [S. Andrea Hospital, Nuclear Medicine Department, La Spezia (Italy)

2017-09-15

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [{sup 11}C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging. (orig.)

Production of PET radiopharmaceutical 18F-FDG using synthesizer automatic module

International Nuclear Information System (INIS)

Purwoko; Chairuman; Adang Hardi Gunawan; Yayan Tahyan; Eny Lestari; Sri Aguswarini Lestiyowati; Karyadi; Sri Bagiawati

2010-01-01

Radiopharmaceutical 2-( 18 F)Fluoro-2-Deoxy-D-Glucose or 18 F(FDG) is an important PET (Positron Emission Tomography) radiopharmaceutical for tumour imaging. In the PET technique glucose metabolism in tumour tissues can be determined quantitatively and used for diagnosis staging and monitoring of treatment tumour or cancer disease in medical oncology. The production of 2-( 18 F)Fluoro-2-Deoxy-D-Glucose 18 F-FDG using compact automated system module TRACERlab MX has been carried out. The modular setup of the apparatus permits reliable for routine synthesis of radiopharmaceuticals 18 F-FDG based on kriptofix mediated nucleophilic fluorination to mannose triflate precursor. Radiochemical yield of 18 F-FDG was 53.895 % (decay time uncorrected) in 40 minutes. The product showed that the colorless and clear solution at pH:6, sterile and pirogen free, kriptofix impurities was low and radiochemical purity was 99.595%. (author)

Efficient synthesis of a fluorine-18 labeled biotin derivative.

Science.gov (United States)

Claesener, Michael; Breyholz, Hans-Jörg; Hermann, Sven; Faust, Andreas; Wagner, Stefan; Schober, Otmar; Schäfers, Michael; Kopka, Klaus

2012-11-01

The natural occurring vitamin biotin, also known as vitamin H or vitamin B(7), plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10(-15)M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [(18)F]4 for a potential application in positron emission tomography (PET). Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [(18)F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Compound [(18)F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. An efficient synthesis for [(18)F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [(18)F]4. Copyright © 2012 Elsevier Inc. All rights reserved.

Detection of occult bone metastases of lung cancer with Fluorine-18 fluorodeoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Foo, S.S.; Ramdave, S.; Berlangieri, S.U.; Scott, A.M.

2004-01-01

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastasesin patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans. Copyright (2004) Blackwell Science Pty Ltd

Synthesis and Pharmacological Evaluation of [11C]Granisetron and [18F]Fluoropalonosetron as PET Probes for 5-HT3 Receptor Imaging.

Science.gov (United States)

Mu, Linjing; Müller Herde, Adrienne; Rüefli, Pascal M; Sladojevich, Filippo; Milicevic Sephton, Selena; Krämer, Stefanie D; Thompson, Andrew J; Schibli, Roger; Ametamey, Simon M; Lochner, Martin

2016-11-16

Serotonin-gated ionotropic 5-HT 3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT 3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril) and palonosetron (Aloxi), belong to a family of drugs (the "setrons") that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15) that has a binding affinity (K i = 0.26 ± 0.05 nM) similar to the parent drug (K i = 0.21 ± 0.03 nM). We radiolabeled 15 by nucleophilic 18 F-fluorination of an unsymmetrical diaryliodonium palonosetron precursor and achieved the radiosynthesis of 1-(methyl- 11 C)-N-granisetron ([ 11 C]2) through N-alkylation with [ 11 C]CH 3 I, respectively. Both compounds [ 18 F]15 (chemical and radiochemical purity >95%, specific activity 41 GBq/μmol) and [ 11 C]2 (chemical and radiochemical purity ≥99%, specific activity 170 GBq/μmol) were evaluated for their utility as positron emission tomography (PET) probes. Using mouse and rat brain slices, in vitro autoradiography with both [ 18 F]15 and [ 11 C]2 revealed a heterogeneous and displaceable binding in cortical and hippocampal regions that are known to express 5-HT 3 receptors at significant levels. Subsequent PET experiments suggested that [ 18 F]15 and [ 11 C]2 are of limited utility for the PET imaging of brain 5-HT 3 receptors in vivo.

NCA nucleophilic radiofluorination on substituted benzaldehydes for the preparation of [18F]fluorinated aromatic amino acids

International Nuclear Information System (INIS)

Wadsak, Wolfgang; Wirl-Sagadin, Barbara; Mitterhauser, Markus; Mien, Leonhard-Key; Ettlinger, Dagmar E.; Keppler, Bernhard K.; Dudczak, Robert; Kletter, Kurt

2006-01-01

Nucleophilic aromatic substitution is a challenging task in radiochemistry. Therefore, a thorough evaluation and optimisation of this step is needed to provide a satisfactory tool for the routine preparation of [ 18 F]fluorinated aromatic amino acids. Two methods, already proposed elsewhere, were evaluated and improved. The yields for the radiofluorination were increased whereas activity loss during solid phase extraction was observed. Radiochemical yields for the two methods were 92.7±5.5% (method 1) and 92.1±12.3% (method 2) for conversion and 11.1±2.8% (method 1) and 34.8±0.6% (method 2) for purification, respectively. In total, we demonstrate an optimised method for the preparation of this important class of [ 18 F]fluorinated synthons for PET

The role of 18F-FDG PET in characterising disease activity in Takayasu arteritis

International Nuclear Information System (INIS)

Webb, Myles; Chambers, Anthony; AL-Nahhas, Adil; Maudlin, Lucy; Rahman, Lucy; Frank, John; Mason, Justin C.

2004-01-01

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 18 F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists' criteria for TA. 18 F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that 18 F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment. (orig.)

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer

International Nuclear Information System (INIS)

Kosuda, S.; Kison, P.V.; Greenough, R.; Grossman, H.B.; Wahl, R.L.

1997-01-01

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000-3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine. (orig.). With 3 figs., 1 tab

Regulatory requirements for fluorine 18-labelled radiotracers

International Nuclear Information System (INIS)

Prigent, A.

2005-01-01

Although European and French regulations define radiopharmaceuticals and their different conditions for use, there is no legal status of the radiotracer. Radiotracer is commonly known as a molecular entity administered in tracer doses, that means at very low masses (e.g., nano-mol amounts) and, consequently, without any pharmacological effect. A radiotracer can meet the specifications of either a radiochemical (usually restricted to research in animal models) or a radiopharmaceutical (human use for diagnostic imaging or research projects). Besides the 'proprietary medicinal product', different status have been defined to allow other uses in humans, referring to 'magistral formula' preparation, 'officinal formula' preparation, investigational medicinal product for clinical trials, or to a radiopharmaceutical with a 'patient named authorization'. However, because of the short half-life of fluorine 18 and expanding development of molecular imaging techniques using positron emission tomography (PET), the current regulation is sometimes considered as inappropriate with regard to the small-size production required for such on-site manufactured radiopharmaceuticals. It is often claimed that it could be very difficult to comply with the current Good Manufactured Practice (cGMP). As previously done for radiopharmaceuticals based on monoclonal antibodies, specific adjustments for PET radiopharmaceuticals are under discussion and the 'note for guidance on radiopharmaceuticals' will be soon revised by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA). In many cases, a status of 'magistral' product might be attributed to a PET radiopharmaceutical manufactured according with European Pharmacopoeia monographs. (author)

First (18)F-labeled ligand for PET imaging of uPAR

DEFF Research Database (Denmark)

Persson, Morten; Liu, Hongguang; Madsen, Jacob

2013-01-01

Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA......-conjugated version (NOTA-AE105) for development of the first (18)F-labeled uPAR positron-emission-tomography PET ligand using the Al(18)F radiolabeling method. In this study, the potential of (18)F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated....

Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

Energy Technology Data Exchange (ETDEWEB)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

2010-03-15

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

Radiolabeled cypoxic cell sensitizers: tracer for assessment of ischemia

International Nuclear Information System (INIS)

Mathias, C.J.; Welch, M.J.; Kilbourn, M.R.; Jerabek, P.A.; Patrick, T.B.; Raichle, M.E.; Krohn, K.A.; Rasey, J.S.; Shaw, D.W.

1987-01-01

Hypoxic, non-functional, but viable, tissue may exist in heart and brain following an arterial occlusion. Identification of such tissue in vivo is crucial to the development of effective treatment strategies. It has been suggested that certain compounds capable of sensitizing hypoxic tumor cells to killing by x-rays (i.e., misonidazole) might serve as in vivo markers of hypoxic tissue in ischemic myocardium or brain if properly radiolabeled. To this end the authors have radiolabeled two fluorinated analogs of nitroimidazole based hypoxic cell sensitizers with the 110 minute half-lived positron-emitting fluorine-18. The ability of these tracers to quantitate the presence of hypoxic tissue has been studied in a gerbil stroke model. The in vivo uptake of one of these tracers [F-18]-fluoronormethyoxymisonidazole is dependent on the extent of tissue hypoxia, and thus, appears to have potential as a diagnostic indicator of non-functional but viable tissue when the tracer is used in conjunction with positron emission tomography. 80 references, 2 figures, 1 table

Fluorine-18-Fluorodeoxyglucose PET in the mediastinal nodal staging of bronchogenic carcinoma.

Energy Technology Data Exchange (ETDEWEB)

Berlangieri, S.U.; Scott, A.M.; Knight, S.; Pointon, O.; Thomas, D.L.; O``Keefe, G.; Chan, J.G.; Egen, G.F.; Tochon-Danguy, H.J.; Clarke, C.P.; McKay, W.J. [Austin Hospital, Melbourne, VIC (Australia). Centre for Positron Emission Tomography and the Departments of Nuclear Medicine and Thoracic Surgery

1998-03-01

Full text: Non-invasive methods of pre-operative staging of non-small cell bronchogenic carcinoma are inaccurate. To determine the clinical role of positron emission tomography (PET) in the mediastinal staging of lung carcinoma, {sup 18}F-fluorodeoxyglucose (FDG) studies were performed in 25 patients with suspected non-small cell bronchogenic carcinoma and correlated with pathology. The patients comprised 20 men and 5 women (mean age 63; range 43-78 y). All patients had proven non-small cell lung carcinoma, except two, one patient with benign inflammatory disease and the other with small cell carcinoma. The FDG PET studies were acquired on a Siemens 951131R body tomography over 2-3 bed positions to include the thorax and mediastinum. The PET images were interpreted for tumour involvement of mediastinal nodes according to the American Thoracic Society classification and scored for confidence of tumour presence on a 5 point scale. The intensity of glucose metabolism was compared to mediastinal blood pool activity and graded on a 4 point scale. FDG PET correctly excluded ipsilateral mediastinal nodal (N2) disease in 16 of 16 patients. Six of nine patients with N2 disease were correctly identified by FDG PET. Of the three patients with N2 nodal involvement not detected by PET, each had single station nodal disease, and in two patients the primary lesions abutted the involved nodal group. A total of 104 nodal stations were sampled or examined at surgery. FDG PET correctly excluded disease in 83/83 (100% specificity) negative nodal stations. FDG PET is a promising non-invasive functional imaging modality for the mediastinal staging of bronchogenic carcinoma.

Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Ramdave, Shankar; Berlangieri, Salvatore U.

2004-01-01

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans Copyright (2004) Blackwell Publishing Asia Pty Ltd

PET radiochemistry: synthesis of 2-[{sup 18} F]-fluorine-2-deoxy-D-glucose; Radioquimica PET: sintesis de 2-[{sup 18} F]-fluor-2-desoxi-D-glucosa

Energy Technology Data Exchange (ETDEWEB)

Lopez D, F A; Flores M, A; Zarate M, A; Romo, E [Unidad PET-Ciclotron, Facultad de Medicina, UNAM, Ciudad Universitaria, 04510 Mexico D.F. (Mexico)

2005-07-01

The present work describes the method for the synthesis of the 2-[{sup 18}F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

Science.gov (United States)

Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

2013-12-01

(18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

Energy Technology Data Exchange (ETDEWEB)

Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

1997-10-01

Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

Clinical significance of incidental focal bowel uptake on ¹⁸F-FDG PET/CT as related to colorectal cancer

DEFF Research Database (Denmark)

Soltau, Sofus Rønne; Hess, Søren; Nguyen, Tram

2016-01-01

OBJECTIVE: Increased focal colorectal uptake of fluorine-18-fluorodeoxyglucose ((18)F-FDG) is reported to occur in 1%-3% of patients undergoing (18)F-FDG positron emission tomography/computed tomography (PET/CT) for disease outside the bowel. However, there is no consensus on how to deal with thi......OBJECTIVE: Increased focal colorectal uptake of fluorine-18-fluorodeoxyglucose ((18)F-FDG) is reported to occur in 1%-3% of patients undergoing (18)F-FDG positron emission tomography/computed tomography (PET/CT) for disease outside the bowel. However, there is no consensus on how to deal...... with this finding in the clinic. Due to the non-specific appearance of such lesions and a certain rate of false positive findings, patients may by subjected to unnecessary invasive procedures or, conversely, cancers may be overlooked if the risk of malignancy is downplayed. The purpose of this study was to examine...

Fluorine-18 labeled tetrahydrocannabinol: Synthesis and PET studies in a boron

International Nuclear Information System (INIS)

Marciniak, G.; Charalambous, A.; Makriyannis, A.; Shiue, C.Y.; Dewey, S.L.; Schlyer, D.J.; Wolf, A.P.

1990-01-01

Cannabinoids, the active components of marijuana are known to be psychotic. The most active components of this class of compound are delta-9-tetrahydrocannabinol (Δ 9 -THC) and its delta-8 isomer. While Δ 8 -THC and Δ 9 -THC have similar psychotic activity, Δ 8 -THC is more stable than its Δ 9 analog. Recently, several cannabinoids are found to have high binding affinity to the brain. However, little is known about the mechanisms of their actions. In order to study its pharmacokinetic in animals, the authors have synthesized fluorine-18 labeled 5'-fluoro-Δ 8 -THC and studied its distribution in mice and in a baboon brain

The role of {sup 18}F-FDG PET in characterising disease activity in Takayasu arteritis

Energy Technology Data Exchange (ETDEWEB)

Webb, Myles; Chambers, Anthony; AL-Nahhas, Adil; Maudlin, Lucy; Rahman, Lucy; Frank, John [Department of Nuclear Medicine, Hammersmith Hospital, Du Cane Road, W12 0HS, London (United Kingdom); Mason, Justin C. [Department of Rheumatology, Hammersmith Hospital, London (United Kingdom)

2004-05-01

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 {sup 18}F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists' criteria for TA. {sup 18}F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that {sup 18}F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment. (orig.)

Diagnostic performance of fluorine-18-dihydroxyphenylalanine positron emission tomography in diagnosing and localizing the focal form of congenital hyperinsulinism: a meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Mirk, Paoletta; Giordano, Alessandro; Rufini, Vittoria

2012-11-01

We performed a meta-analysis on published data on the diagnostic performance of fluorine-18 dihydroxyphenylalanine ((18)F-DOPA) positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). A comprehensive computer literature search of studies published up to 31 January 2012 regarding (18)F-DOPA PET or PET/CT in patients with CHI was performed. Pooled sensitivity and specificity, area under the ROC curve and diagnostic odds ratio (DOR) of (18)F-DOPA PET or PET/CT in diagnosing focal CHI were calculated. The localization accuracy of focal CHI was also estimated. Seven studies comprising 195 CHI patients were included. The pooled sensitivity and specificity of (18)F-DOPA PET or PET/CT in differentiating between focal and diffuse CHI were 89% (95% confidence interval [CI]:81-95%) and 98% (95% CI:89-100%), respectively. The DOR was 74.5 (95% CI:18-307). The area under the ROC curve was 0.95. The pooled accuracy of these functional imaging methods in localizing focal CHI was 80% (95% CI:71-88%). In CHI patients, (18)F-DOPA PET or PET/CT demonstrated high sensitivity and specificity in differentiating between focal and diffuse CHI. (18)F-DOPA PET or PET/CT are accurate methods of localizing focal CHI. Nevertheless, possible sources of false-negative results for focal CHI should be kept in mind.

PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

Energy Technology Data Exchange (ETDEWEB)

Page, R.L.; Garg, P.K.; Gard, S. [North Carolina State Univ., Raleigh, NC (United States)]|[Duke Univ. Medical Center, Durham, NC (United States)]|[North Carolina and Norke Radium Hospital, Oslo (Norway)] [and others

1994-09-01

Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the {sup 18}F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4{prime}-({sup 18}F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T{sub 1/2{beta}} = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of {sup 18}F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10{sup -3}% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of {sup 18}F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs.

PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

International Nuclear Information System (INIS)

Page, R.L.; Garg, P.K.; Gard, S.

1994-01-01

Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the 18 F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4'-( 18 F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T 1/2β = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of 18 F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10 -3 % injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of 18 F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs

Cerebral Toxoplasmosis in a Patient with AIDS on F-18 FDG PET/CT

International Nuclear Information System (INIS)

Kim, Hae Won; Won, Kyung Sook; Choi, Byung Wook; Zeon, Seok Kil

2010-01-01

The distinction between primary central nervous system (CNS) lymphoma and nonmalignant lesions due to opportunistic infections, in particular cerebral toxoplasmosis, is important because of the different treatments involved. A 32-year-old patient with AIDS was hospitalized for intermittent headaches. Brain magnetic resonance imaging (MRI) showed a small well-enhanced nodular lesion in the right frontal lobe. A fluorine-18 fluorodeoxyglucose (F-18 FDG) position emission tomography (PET)/ computed tomography (CT) scan showed moderate FDG uptake in the nodular lesion of the right frontal lobe. We present a case of cerebral toxoplasmosis in a patient with acquired immunodeficiency syndrome (AIDS) and the usefulness of F-18 FDG PET/CT in the differential diagnosis of the cerebral toxoplasmosis will be discussed.

Cerebral Toxoplasmosis in a Patient with AIDS on F-18 FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Kim, Hae Won; Won, Kyung Sook; Choi, Byung Wook; Zeon, Seok Kil [Keimyung University School of Medicine, Daegu (Korea, Republic of)

2010-04-15

The distinction between primary central nervous system (CNS) lymphoma and nonmalignant lesions due to opportunistic infections, in particular cerebral toxoplasmosis, is important because of the different treatments involved. A 32-year-old patient with AIDS was hospitalized for intermittent headaches. Brain magnetic resonance imaging (MRI) showed a small well-enhanced nodular lesion in the right frontal lobe. A fluorine-18 fluorodeoxyglucose (F-18 FDG) position emission tomography (PET)/ computed tomography (CT) scan showed moderate FDG uptake in the nodular lesion of the right frontal lobe. We present a case of cerebral toxoplasmosis in a patient with acquired immunodeficiency syndrome (AIDS) and the usefulness of F-18 FDG PET/CT in the differential diagnosis of the cerebral toxoplasmosis will be discussed.

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma

International Nuclear Information System (INIS)

Quartuccio, Natale; Treglia, Giorgio; Salsano, Marco; Mattoli, Maria Vittoria; Muoio, Barbara; Piccardo, Arnoldo; Lopci, Egesta; Cistaro, Angelina

2013-01-01

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS). A comprehensive literature search of published studies through October 10 th , 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning

[18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

International Nuclear Information System (INIS)

Gruender, G.; Lange-Asschenfeldt, C.; Vernaleken, I.; Lueddens, H.; Siessmeier, T.; Buchholz, H.-G.; Bartenstein, P.; Stoeter, P.; Drzezga, A.; Roesch, F.

2001-01-01

5-(2'-[ 18 F]Fluoroethyl)flumazenil ([ 18 F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [ 11 C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [ 18 F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [ 18 F]FEF and with [ 11 C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4±2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [ 18 F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [ 18 F]FEF compared with [ 11 C]flumazenil, while relative uptake of [ 18 F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the α6 subunit. Metabolism of [ 18 F]FEF was very

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

International Nuclear Information System (INIS)

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna; Frech, Andreas; Fraedrich, Gustav; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias

2013-01-01

18 F-Fluoro-l-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68 Ga-DOTA-Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) PET. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC PET and 18 F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV max ) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, 68 Ga-DOTA-TOC PET and 18 F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68 Ga-DOTA-TOC was 100 % and that of 18 F-DOPA PET was 56.0 %. Overall, 68 Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18 F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68 Ga-DOTA-TOC PET was 100 % (McNemar, P 18 F-DOPA PET was 71.1 % (McNemar, P max (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for 68 Ga-DOTA-TOC PET and 11.8 ± 7.9 for 18 F-DOPA PET (Mann-Whitney U test, P 68 Ga-DOTA-TOC PET may be superior to 18 F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically

SiRNAs in vivo imaging: methodology of fluorine-18 radiolabelling and application for the optimization of the siRNAs biodistribution and pharmaceutical properties; Imagerie in vivo des ARN interferentiels: methodologie de marquage au fluor-18 et application pour l'optimisation par imagerie de leur biodistribution et de leurs proprietes pharmacologiques

Energy Technology Data Exchange (ETDEWEB)

Viel, Th

2008-01-15

As RNA interference is a natural process which enables eukaryote cells to regulate the gene expressions, to control transposons, and to struggle against some viruses, two imagery techniques have been used in this research, i.e. optical imagery and Positron Emission Tomography (PET) imagery, to study the various modifications of the small interferential RNAs (siRNA). Different chemically modified siRNAs have been prepared and their in vitro activity, their in vivo metabolism (by HPLC analysis), their bio-distribution and their pharmacokinetic properties (by PET imagery) after marking them with fluorine-18. Their in vivo activity has been assessed by optical imagery.

Radiolabeled COX-2 Inhibitors for Non-Invasive Visualization of COX-2 Expression and Activity — A Critical Update

Directory of Open Access Journals (Sweden)

Torsten Kniess

2013-05-01

Full Text Available Cyclooxygenase-2 (COX-2 is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET and single photon emission computed tomography (SPECT since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[18F]fluorination or de[11C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field.

Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study.

Science.gov (United States)

Hartimath, Siddesh V; Manuelli, Valeria; Zijlma, Rolf; Signore, Alberto; Nayak, Tapan K; Freimoser-Grundschober, Anne; Klein, Christian; Dierckx, Rudi A J O; de Vries, Erik F J

2018-01-23

Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET. [ 18 F]FB-IL2v binds specifically to IL2 receptors (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared mainly by the kidneys (Balb/c mice). [ 18 F]FB-IL2v PET studies in SCID mice injected with hPBMCs revealed high uptake in the implant (0.85 ± 0.15 SUV), which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v (SUV 0.26 ± 0.1 and 0.46 ± 0.1, p FB-IL2v to IL2R was reversible. The volume of distribution (V T ) and the non-displaceable binding potential (BP nd ) of mutant [ 18 F]FB-IL2v in the implant were approximately 3 times lower than those of wild-type [ 18 F]FB-IL2 ( p FB-IL2v in the implant ( p FB-IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes it less suitable as a therapeutic drug. [ 18 F]FB-IL2v, on the other hand, seems to have better properties for use as a therapeutic drug.

Synthesis of [18F] labeled tetraphenylphosphonium derivatives as a novel myocardial perfusion agent for PET

International Nuclear Information System (INIS)

Kim, Dong Yeon; Bom, Hee Seung; Min, Jung Joon; Yu, Kook Hyun

2007-01-01

Lipophilic cations including phosphonium salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular 'voltage sensor' probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Besides, the tetraphenylphosphonium (TPP) salts has been known to be accumulated in cancer cells as well as in cardiomyocytes especially, [18F]labeled tetraphenylphosphonium derivativesare thought to have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. We have synthesized a reference compound fluoroalkyl triphenylphosphonium (n=5, 6, 7, 8) and a labeled compound, [18F]fluoroalkyl triphenylphosphonium (n=5, 6, 7, 8), which via two step nucleophilic substitution of no-carrier-added F-18 fluoride with the precurso in the presence of Kryptofix-2.2.2 and K2CO3. The reference compound fluoroalkyl triphenylphosphonium (n=5, 6, 7, 8) were synthesized in 79∼82% yield and the labeled compound were synthesized in 20∼25% yield respectively. The tetraphenylphosphonium (TPP) salts exhibited accumulation in cancer as well as heart. Therefore, [18F] radiolabeled tetraphenylphosphonium derivatives are thought to have a potential being utilized as a novel PET molecular probe for imaging cancer and myocardium. Thus, the development of [18F] radiolabeled tetraphenylphosphonium derivatives as a noninvasive imaging agent may serve as a new molecular voltage sensor probe to investigate the role of mitochondria in the diagnosis and treatment of ischemic heart disease and cancer

Chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) with massive vertebral bone erosion: computed tomography (CT), magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings.

Science.gov (United States)

Nakano, Sachiko; Okauchi, Kenzo; Tsushima, Yoshito

2014-02-01

A 62-year-old male presented with sudden onset of low back and right leg pain. Contrast-enhanced computed tomography demonstrated an abdominal aortic aneurysm (AAA), along with a large mass lesion causing vertebral body erosion. Magnetic resonance imaging (MRI) suggested that the mass lesion consisted of a chronic hematoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated increased uptake around the mass lesion, but not around the AAA. Surgical intervention was performed, and the subsequent histological diagnosis was chronic contained rupture of AAA. The mass lesion consisted of chronic hematoma and necrosis with inflammatory cell infiltration and hemosiderin deposition. This condition mimics some neoplastic diseases, but MRI and FDG-PET findings may help establish the correct diagnosis.

Production of fluorine-18 from eithium carbonate in a research reactor

International Nuclear Information System (INIS)

Gasiglia, H.T.

1978-01-01

A method for the production of fluorine-18 in a research reactor, from irradiated lithium carbonate, is described. Fluorine-18 is separated from impurities in a alumina column, which is an appropriate procedure for its production as a carrier-free radioisotope for oral administration. Characteristics of the product, when fluorine is separated from irradiated target in an usual alumina column, are compared with those when fluorine is separated in a previously calcined(1000 0 C) alumina column: Yields of chemical separation and chemical forms of radioisotope obtained are studied. Fluorine elution is investigated for several eluant concentrations and the use of a lower concentrated eluant is emphasized. Purity degree of fluorine-18 solutions separated. A routine production procedure is determined by irradiating enriched lithium carbonate (95% 6 Li). Theoretical yields are compared with fluorine-18 production yields obtained in several irradiations [pt

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole

International Nuclear Information System (INIS)

Liu Renshyan; Chu Leeshing; Yen Sanhui; Chang Chenpei; Chou Kuoliang; Wu Liangchi; Chang Chiwei; Lui Muntain; Chen Kuangy; Yeh Shinhwa

1996-01-01

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodonititis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental carries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively. 18 F-fluoride ion bone scan done in three patients showed that 18 F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy. (orig.)

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole

Energy Technology Data Exchange (ETDEWEB)

Liu Renshyan [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China); Chu Leeshing [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China)]|[National Defense Medical Center, Taipei (Taiwan); Yen Sanhui [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China)]|[National Defense Medical Center, Taipei (Taiwan); Chang Chenpei [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China); Chou Kuoliang [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China); Wu Liangchi [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China); Chang Chiwei [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China); Lui Muntain [Dept. of Dentistry, Taipei Veterans General Hospital (Taiwan, Province of China); Chen Kuangy [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China)]|[National Defense Medical Center, Taipei (Taiwan); Yeh Shinhwa [National PET/Cyclotron Center and Dept. of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming Univ. Medical School, Taipei (Taiwan, Province of China)

1996-10-01

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodonititis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental carries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively. {sup 18}F-fluoride ion bone scan done in three patients showed that {sup 18}F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy. (orig.)

{sup 18}F-PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, {sup 18}F-labelling and an in-vitro assessment of its binding with Neutravidin{sup TM}-trastuzumab pre-treated cells

Energy Technology Data Exchange (ETDEWEB)

Smith, Tim A.D., E-mail: t.smith@abdn.ac.uk [Biomedical Physics Building, John Mallard PET Unit, Aberdeen Biomedical Imaging Centre, School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Simpson, Michael; Cheyne, Richard [Biomedical Physics Building, John Mallard PET Unit, Aberdeen Biomedical Imaging Centre, School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Trembleau, Laurent [School of Natural and Computing Sciences, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom)

2011-10-15

In terms of nuclear decay {sup 18}F is the most ideal PET nuclide but its short t{sub 1/2} precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin{sup TM}-biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin{sup TM}-conjugated antibodies. Methods: Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with {sup 18}F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin{sup TM}-conjugated trastuzumab, washed, and then incubated with {sup 18}F-PEG-biotin. Results: The {sup 18}F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel {sup 18}F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin{sup TM}-conjugated trastuzumab. Conclusion: Biotin can be functionalised with boroaryl and readily {sup 18}F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin{sup TM}-antibody conjugates. - Highlights: > Boroaryl-biotin precursor is prepared. > Rapid {sup 18}F-fluorination is demonstrated. > HER-2 expressing breast cancer cells pre-treated with trastuzumab-Neutravidin{sup TM}. > {sup 18}F-PEG-biotin binding to pre-treated cells corresponds with HER-2 expression.

The determination of patient dose from 18F-FDG PET/CT examination

International Nuclear Information System (INIS)

Khamwan, K.; Krisanachinda, A.; Pasawang, P.

2010-01-01

The use of positron emission tomography/computed tomography (PET/CT) system has heightened the need for medical diagnosis. However, the patient dose is increasing in comparison to whole-body PET/CT dose. The aim of this study is to determine the patient effective dose in 35 oncology Thai patients with the age range of 28-60 y from PET scan using [fluorine-18]-fluoro-2-deoxy-D-glucose and from CT scan. Cumulated activity and residence time of various organs were calculated from time-activity curves by using S-value based on the body mass. Mean organ absorbed dose and the effective dose from CT scan were calculated using the Medical Internal Radiation Dosimetry method and Monte Carlo simulation, respectively. The average whole-body effective doses from PET and CT were 4.40 ± 0.61 and 14.45 ± 2.82 mSv, respectively, resulting in the total patient dose of 18.85 mSv. This can be used as the reference dose in Thai patients. (authors)

The role of 18F-FDG PET and PET/CT in the evaluation of primary cutaneous lymphoma.

Science.gov (United States)

Qiu, Lin; Tu, Guojian; Li, Jing; Chen, Yue

2017-02-01

Primary cutaneous lymphoma (PCL) is the second most common type of extranodal non-Hodgkin lymphoma, including both cutaneous T-cell and B-cell lymphomas. PCL comprises numerous subtypes and thus has myriad clinical presentations in the skin and subcutaneous tissues. Accurate classification and staging are important for making treatment recommendations for PCL and will further impact patient prognosis significantly. We review the role of fluorine-18-fluorodeoxyglucose (F-FDG) PET (F-FDG PET) and F-FDG PET with computed tomography (CT) in the diagnosis, staging, tumor biological evaluation, treatment response assessment, and early recurrence surveillance of PCL. Although F-FDG PET and PET/CT do not seem to adequately distinguish the plaque, patch, or erythroderma cutaneous lesions of PCL, the imaging modalities are superior to CT, MRI, and other nuclear medicine methods in detecting both the cutaneous and the extracutaneous lesions of PCL. The available literature addressing the clinical role of F-FDG PET and PET/CT in patients with PCL is promising for the use of the modalities in staging, tumor biological evaluation, biopsy guidance, early treatment response assessment, and recurrence surveillance. However, more data are needed to better specify the role of F-FDG PET and PET/CT in the management of PCL.

[F-18]fluoro-meta-L-tyrosine is a better PET tracer than [F-18]fluoro-L-dopa for the delineation of dopaminergic structures in the human brain

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

Fluorine-18 labelled fluoro-m-L-tyrosine (FmLtyr) and fluoro-L-Dopa (F-Dopa) have been synthesized, and the utility of FmLtyr for PET investigations of dopaminergic brain regions has been compared to that of F-dopa. Experimental results from both monkey and human studies indicate that FmLtyr gives better delineation of striatum, and is a better PET tracer than F-dopa

Consultants' meeting on reactor production and utilization of Fluorine-18

International Nuclear Information System (INIS)

Vera Ruiz, H.

1986-08-01

The nuclear research reactors with thermal neutron fluxes in the order of 1x10 13 cm -2 s -1 can produce sufficient quantities of fluorine-18 for biomedical applications. The recent improvements in labelling with fluorine-18 via nucleophilic reactions have made it possible to develop efficient synthesis techniques for preparing useful quantities of radiopharmaceuticals, which are of great interest for studying regional metabolic functions with positron emission tomography. Other non-medical activities in the field of pharmacology, toxicology, no-carrier-added syntheses and reaction mechanisms in fluorine chemistry can also conveniently be studied using fluorine-18 as a tracer

One-step preparation of [18F]FPBM for PET imaging of serotonin transporter (SERT) in the brain

International Nuclear Information System (INIS)

Qiao, Hongwen; Zhang, Yan; Wu, Zehui; Zhu, Lin; Choi, Seok Rye; Ploessl, Karl; Kung, Hank F.

2016-01-01

Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [ 18 F]FPBM, 2-(2′-(dimethylamino)methyl)-4′-(3-([ 18 F]fluoropropoxy)phenylthio) benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [ 18 F]F − /K 222 to produce [ 18 F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [ 18 F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [ 18 F]FPBM (radiochemical yield, 24–33%, decay corrected; radiochemical purity > 99%). PET imaging studies in normal monkeys (n = 4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5 mg/kg iv injection at 30 min after [ 18 F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [ 18 F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [ 18 F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [ 18 F]FPBM for in vivo PET imaging of SERT binding in the brain.

Semi-automated preparation of the dopamine transporter ligand [18F]FECNT for human PET imaging studies

International Nuclear Information System (INIS)

Voll, Ronald J.; McConathy, Jonathan; Waldrep, Michael S.; Crowe, Ronald J.; Goodman, Mark M.

2005-01-01

The fluorine-18 labeled dopamine transport (DAT) ligand 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (FECNT) has shown promising properties as an in vivo DAT imaging agent in human and monkey PET studies. A semi-automated synthesis has been developed to reliably produce [ 18 F]FECNT in a 16% decay corrected yield. This method utilizes a new [ 18 F]fluoralkylating agent and provides high purity [ 18 F]FECNT in a formulation suitable for human use

Metabolic 19F MRI an dynamic 18F PET for chemotherapy monitoring in experimental tumors

International Nuclear Information System (INIS)

Brix, G.; Haberkorn, U.; Bellemann, M.E.

1999-01-01

The efficient clinical use of chemotherapeutic agents requires the assessment of the uptake and metabolism of the drugs in the tumor as well as in the various organs of the body by using noninvasive imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET). In this overview, we present different metabolic 19 F MRI and dynamic 18 F PET techniques for noninvasive monitoring of fluorine-containing anticancer drugs and evaluate their potentials and limitations within the framework of experimental animal studies. (orig.) [de

Chronic contained rupture of abdominal aortic aneurysm (CCR-AAA) with massive vertebral bone erosion. Computed tomography (CT), magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings

International Nuclear Information System (INIS)

Nakano, Sachiko; Okauchi, Kenzo; Tsushima, Yoshito

2014-01-01

A 62-year-old male presented with sudden onset of low back and right leg pain. Contrast-enhanced computed tomography demonstrated an abdominal aortic aneurysm (AAA), along with a large mass lesion causing vertebral body erosion. Magnetic resonance imaging (MRI) suggested that the mass lesion consisted of a chronic hematoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated increased uptake around the mass lesion, but not around the AAA. Surgical intervention was performed, and the subsequent histological diagnosis was chronic contained rupture of AAA. The mass lesion consisted of chronic hematoma and necrosis with inflammatory cell infiltration and hemosiderin deposition. This condition mimics some neoplastic diseases, but MRI and FDG-PET findings may help establish the correct diagnosis. (author)

Hepatosplenic Candidiasis Detected by 18F-FDG-PET/CT

International Nuclear Information System (INIS)

Albano, Domenico; Bosio, Giovanni; Bertoli, Mattia; Petrilli, Giulia; Bertagna, Francesco

2016-01-01

Hepatosplenic candidiasis is a fungal infection, which mostly affects patients with hematologic malignancies such as leukemia. The pathogenesis of this infection is not clear yet, and the liver is the most commonly affected organ. Diagnosis of hepatosplenic candidiasis can be only established via biopsy, since computed tomography (CT) scan, ultrasonography, and magnetic resonance imaging (MRI) yield non-specific results. The role of fluorine-18 fluorodeoxyglucose positron emission tomography /computed tomography ( 18 F-FDG PET/CT) in diagnosis of hepatosplenic candidiasis remains undetermined, considering a few evidences in the literature. In this case report, we present the case of a 47-year-old patient, affected by acute myeloid leukemia, which was treated with three cycles of chemotherapy, resulting in the development of neutropenia and fever following the last cycle. The 18 F-FDG PET/CT scan showed some foci of intense FDG uptake in the liver and spleen. The subsequent diagnostic investigations (i.e., abdominal CT scan and biopsy) were suggestive of hepatosplenic candidiasis. The patient was started on antifungal treatment with fluconazole. After one month, the clinical conditions were resolved, and the subsequent abdominal CT scan was negative

PET/CT studies of multiple myeloma using {sup 18}F-FDG and {sup 18}F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Goldschmidt, Hartmut; Hose, Dirk [University of Heidelberg, Medical Clinic V, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany); Pan, Leyun; Cheng, Caixia; Dimitrakopoulou-Strauss, Antonia [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

2014-07-15

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) and fluorine-18 sodium fluoride ({sup 18}F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions. The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased {sup 18}F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the {sup 18}F-NaF PET/CT scans were then correlated with those detected on {sup 18}F-FDG PET/CT, which served as a reference. Moreover, the {sup 18}F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach. Whole body {sup 18}F-FDG PET/CT revealed approximately 343 focal lesions while {sup 18}F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in {sup 18}F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with {sup 18}F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal {sup 18}F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with {sup 18}F-NaF PET/CT. In three patients with multiple focal {sup 18}F-FDG-uptake, {sup 18}F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with {sup 18}F-FDG and {sup 18}F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of {sup 18}F-FDG revealed the

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

DEFF Research Database (Denmark)

Jakobsen, Annika Loft; Andersson, A P; Dahlstrøm, K

2000-01-01

Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty......-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography...

One-Step 18F-Labeling of Estradiol Derivative for PET Imaging of Breast Cancer

Directory of Open Access Journals (Sweden)

Hongbo Huang

2018-01-01

Full Text Available Positron emission tomography (PET imaging is a useful method to evaluate in situ estrogen receptor (ER status for the early diagnosis of breast cancer and optimization of the appropriate treatment strategy. The 18F-labeled estradiol derivative has been successfully used to clinically assess the ER level of breast cancer. In order to simplify the radiosynthesis process, one-step 18F-19F isotope exchange reaction was employed for the 18F-fluorination of the tracer of [18F]AmBF3-TEG-ES. The radiotracer was obtained with the radiochemical yield (RCY of ~61% and the radiochemical purity (RCP of >98% within 40 min. Cell uptake and blocking assays indicated that the tracer could selectively accumulate in the ER-positive human breast cancer cell lines MCF-7 and T47D. In vivo PET imaging on the MCF-7 tumor-bearing mice showed relatively high tumor uptake (1.4~2.3 %D/g and tumor/muscle uptake ratio (4~6. These results indicated that the tracer is a promising PET imaging agent for ER-positive breast cancers.

Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

Science.gov (United States)

Sun, Aixia; Liu, Xiang; Tang, Ganghua

2017-12-01

Tumor cells have an increased nutritional demand for amino acids(AAs) to satisfy their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting probes and are of great importance for imaging tumors using positron emission tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] amino acids, labeling alpha-C- amino acids, the branched-chain of amino acids and N-substituted carbon-11 labeled amino acids. These tracers target protein synthesis or amino acid(AA) transport, and their uptake mechanism mainly involves AA transport. AA PET tracers have been widely used in clinical settings to image brain tumors, neuroendocrine tumors, prostate cancer, breast cancer, non–small cell lung cancer (NSCLC) and hepatocellular carcinoma. This review focuses on the fundamental concepts and the uptake mechanism of AAs, AA PET tracers and their clinical applications.

Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the postchemotherapy management of patients with seminoma: systematic review and meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Caldarella, Carmelo; Bertagna, Francesco; Giovanella, Luca

2014-01-01

To meta-analyze published data about the diagnostic performance of fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the postchemotherapy management of patients with seminoma. A comprehensive literature search of studies published through January 2014 on this topic was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity and specificity, positive and negative predictive values (PPV and NPV), accuracy, and area under the summary ROC curve (AUC) of (18)F-FDG-PET or PET/CT on a per examination-based analysis were calculated. Subgroup analyses considering the size of residual/recurrent lesions were carried out. Nine studies including 375 scans were selected. The pooled analysis provided the following results: sensitivity 78% (95% confidence interval (95% CI): 67-87%), specificity 86% (95% CI: 81-89%), PPV 58% (95% CI: 48-68%), NPV 94% (95% CI: 90-96%), and accuracy 84% (95% CI: 80-88%). The AUC was 0.90. A better diagnostic accuracy of (18)F-FDG-PET or PET/CT in evaluating residual/recurrent lesions >3 cm compared to those sources of false-negative and false-positive results should be considered. The literature focusing on this setting still remains limited and cost-effectiveness analyses are warranted.

[18F]FDG PET/CT outperforms [18F]FDG PET/MRI in differentiated thyroid cancer

International Nuclear Information System (INIS)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars; Burg, Matthias Christian; Allkemper, Thomas; Schaefers, Michael

2016-01-01

To evaluate the diagnostic potential of PET/MRI with [ 18 F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [ 18 F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [ 18 F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [ 18 F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [ 18 F]FDG PET/MRI was inferior to low-dose [ 18 F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [ 18 F]FDG PET/MRI was equal to contrast-enhanced neck [ 18 F]FDG PET/CT. Therefore, [ 18 F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast agent is contraindicated. (orig.)

An Assessment of Early Response to Targeted Therapy via Molecular Imaging: A Pilot Study of 3′-deoxy-3′[(18F]-Fluorothymidine Positron Emission Tomography 18F-FLT PET/CT in Prostate Adenocarcinoma

Directory of Open Access Journals (Sweden)

Kalevi Kairemo

2017-04-01

Full Text Available Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (18F-FLT-PET imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (18F-FLT utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (<1%. 18F-FLT-PET could have a role in the evaluation of response to targeted therapy. We present here a pilot study where we investigated cellular metabolism and proliferation in patients with prostate cancer before and after targeted therapy. Seven patients with Stage IV prostate adenocarcinoma, candidates for targeted therapy inhibiting the hepatocyte growth factor/tyrosine-protein kinase Met (HGF/C-MET pathway, were included in this study. The HGF/C-MET pathway is implicated in prostate cancer progression, and an evaluation of the inhibition of this pathway could be valuable. 18F-FLT was performed at baseline and within four weeks post-therapy. Tumor response was assessed semi-quantitatively and using visual response criteria. The range of SUVmax for 18F-FLT at baseline in the prostate varied from 2.5 to 4.2. This study demonstrated that 18F-FLT with positron emission tomography/computerized tomography (18F-FLT PET/CT had only limited applications in the early response evaluation of prostate cancer. 18F-FLT PET/CT may have some utility in the assessment of response in lymph node disease. However, 18F-FLT PET/CT was not found to be useful in the evaluation of the prostate bed, metastatic skeletal disease, and liver disease.

Development and optimization of methods for the radiofluorination of aromatic compounds with specific, high fluorine-18 activity

International Nuclear Information System (INIS)

Franken, K.

1987-06-01

The positron emitter fluorine-18 (T 1/2 = 110 min) is an ideal radionuclide for analogue tracers in positron emission tomography (PET). In this study the production of the electrophilic species [ 18 F]-F 2 , [ 18 F]-CH 3 CO 2 F and to some extent [ 18 F]-XeF 2 has been optimized with respect to yield and specific activity. Selectivity and reactivity of these species have been studied in simple aromatic model compounds. Fluorine was produced via the 20 Ne(d,α) 18 F reaction. The effect of target material, dimensions, amount of carrier (F 2 ), pressure, beam current and irradiation time was studied. Reactivity of [ 18 F]-F 2 and [ 18 F]-CH 3 CO 2 F with respect to hydrogen subsitution was systematically studied in a series of benzene derivatives (C 6 H 5 X, X = CF 3 , I, Br, CL, F, H, CH 3 , OCH 3 , OH) in various solvents (CHCl 3 , CFCl 3 , CH 3 CN, CH 3 OH, CF 3 COOH). The radiochemical yield of 18 F-for-H-substitution in the aromatic ring increased with increasing acceptor number (AN) of the solvent. The electrophilic nature of both fluorination agents was confirmed by a Hammett plot. As expected, [ 18 F]-CH 3 CO 2 F showed a higher selectivity than [ 18 F]-F 2 . Direct radiofluorination with [ 18 F]-F 2 and [ 18 F]-CH 3 CO 2 F was successfully applied to the biomolecules phenylalanine, tyrosine and DOPA. As potential methods for no-carrier-added (n.c.a.) radiofluorination some less common dediazoniation reactions were also studied. (orig./RB) [de

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

International Nuclear Information System (INIS)

Gruenwald, F.; Schomburg, A.; Bender, H.; Klemm, E.; Menzel, C.; Bultmann, T.; Palmedo, H.; Ruhlmann, J.; Kozak, B.; Biersack, H.J.

1996-01-01

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131 I) and a negative FDG PET, in four cases 131 I-negative lymph node metastases were detectable with PET. Even in the patients with concordant ''staging'', differences between 131 I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131 I-positive/FDG-negative, 131 I-negative/FDG-positive and 131 I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131 I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS. (orig.). With 3 figs., 2 tabs

Study on folate receptor PET imaging agent 18F-flurophenethyl folate

International Nuclear Information System (INIS)

Guo Congying; Zhu Jianhua; Qian Jun; Yang Yang; Shen Haixing; Zhang Zhengwei

2009-01-01

This work is aimed at synthesizing an 18 F-labelled folate derivative that can be used as folate-receptor induced tumor PET imaging agent. Under the optimal reaction and testing specification formulated during the cold-labeling experiments, 18 F labeling of folic acid was achieved in three steps of 18 F pre-labeling,bromination and esterification. The receptor binding property of the newly-synthesized folate radio-derivative was studied through β-lactoglobulin binding test. Tumor-bearing nude mice injected with the new compound were used to study whether the derivative can accumulate within tumor issue. Preliminary studies in vitro and in vivo showed that this new PET agent still possessed receptor binding qualities of folic acid. 18 F-flurophenethyl folate remained good affinity and specificity with β-lactoglobulin. Accumulation of activities in tumor tissues was found in tumor-bearing nude mice. A new folate receptor ligand: 18 F-flurophenethyl folate was synthesized,with high yield and good stability. Since the pre-labeling method was used, the fluorine labeling was not directly imposed upon folic acid.In this way, the structure destruction, which happens in high temperature reaction of folic acid, can be avoided. The synthesized folate derivative remained the binding structural quality of folic acid and could bind with the folate-binding protein: β-lactoglobulin. Through the folate receptors located on tumor tissues, 18 F-flurophenethyl folate accumulated in the tumor tissue, exhibiting its potential as a tumor PET imaging agent. (authors)

Central Pontine Myelinolysis and Localized Fluorodeoxyglucose Uptake Seen on 18F-FDG PET/CT

DEFF Research Database (Denmark)

Rønne, Frederik; Tfelt-Hansen, Peer Carsten; Rørdam, Lene

2017-01-01

Case report describing the finding of central pontine myelinolysis (CPM) using combined fluorine-18 ( 18F)-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The patient was a known alcoholic who, during admission was under treatment for hyponatremia, showed...... a significant decline in both motor and cognitive function. Combined 18F-FDG PET/CT showed localized FDG uptake in the pons, consistent with the finding of CPM observed on magnetic resonance imaging (MRI). CPM is a demyelinating lesion of the pons, resulting in several neurological symptoms. The exact cause...... of CPM is not clear, but a strong relations between loss of myelin and osmotic stress exists, especially during rapid correction of hyponatremia. The osmotic stress is thought to induce disruption of the blood-brain barrier, allowing access for inflammatory mediators in extravascular brain tissue, which...

Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

DEFF Research Database (Denmark)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

2016-01-01

Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

A retrospective comparison between {sup 68}Ga-DOTA-TOC PET/CT and {sup 18}F-DOPA PET/CT in patients with extra-adrenal paraganglioma

Energy Technology Data Exchange (ETDEWEB)

Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Frech, Andreas; Fraedrich, Gustav [Innsbruck Medical University, Department of Vascular Surgery, Innsbruck (Austria); Gasser, Rudolf Wolfgang [Innsbruck Medical University, Department of Internal Medicine I, Innsbruck (Austria); Shulkin, Barry Lynn [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Url, Christoph [Innsbruck Medical University, Department of Otorhinolaryngology, Innsbruck (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Prommegger, Rupert [Sanatorium Kettenbruecke, Department of Surgery, Innsbruck (Austria); Sprinzl, Georg Mathias [State Clinic St. Poelten, Department of Otorhinolaryngology, St. Poelten (Austria)

2013-12-15

{sup 18}F-Fluoro-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by {sup 68}Ga-DOTA-Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) PET. Therefore, we compared {sup 68}Ga-DOTA-TOC and {sup 18}F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV{sub max}) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of {sup 68}Ga-DOTA-TOC was 100 % and that of {sup 18}F-DOPA PET was 56.0 %. Overall, {sup 68}Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and {sup 18}F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of {sup 68}Ga-DOTA-TOC PET was 100 % (McNemar, P < 0.5), and that of {sup 18}F-DOPA PET was 71.1 % (McNemar, P < 0.001). The SUV{sub max} (mean {+-} SD) of all 32 concordant lesions was 67.9 {+-} 61.5 for {sup 68}Ga-DOTA-TOC PET and 11.8 {+-} 7.9 for {sup 18}F-DOPA PET (Mann-Whitney U test, P < 0.0001). {sup 68}Ga-DOTA-TOC PET

Value of 18F-FDG PET in the detection of peritoneal carcinomatosis

International Nuclear Information System (INIS)

Suzuki, Akiko; Kawano, Tsuyoshi; Takahashi, Nobukazu; Lee, Jin; Nakagami, Yoshihiro; Inoue, Tomio; Miyagi, Etsuko; Hirahara, Fumiki; Togo, Shinji; Shimada, Hiroshi

2004-01-01

Peritoneal carcinomatosis can be difficult to diagnose using computed tomography (CT). The purpose of this study was to evaluate the role of 2-(fluorine 18) fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the detection of peritoneal carcinomatosis. We reviewed the CT and FDG PET radiological reports and clinical charts of 18 patients with peritoneal carcinomatosis and 17 cancer patients without peritoneal carcinomatosis. We also assessed FDG PET scans from 20 healthy volunteers as a baseline study. The maximum standardised uptake values (SUV max ) over peritoneal lesions in cancer patients and over the area of most intense intestinal uptake in healthy volunteers and cancer patients without peritoneal carcinomatosis were measured. The sensitivity and positive predictive value (PPV) of combined FDG PET and CT were superior to those of CT alone for the detection of peritoneal lesions (sensitivity: 66.7% vs 22.2%, p max threshold of 5.1 produced a diagnostic accuracy of combined FDG PET and CT of 78%. The additional information provided by FDG PET allowed a more accurate diagnosis in 14 patients (40.0%), and led to alteration of the therapeutic strategy in five (14.3%) of the enrolled cancer patients. We found that use of an intra-abdominal FDG uptake cut-off value for SUV max of >5.1 assists in the diagnosis of peritoneal carcinomatosis. FDG PET may play an important role in the clinical management of patients with suspected peritoneal carcinomatosis. (orig.)

Comparison of the performance of {sup 18}F-FP-CIT brain PET/MR and simultaneous PET/CT: A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Kwon, Sang Don; Chun, Kyung Ah [Dept. of Nuclear Medicine, Yeungnam University Hospital, Daegu (Korea, Republic of)

2016-09-15

{sup 18}F-FP-CIT [{sup 1'}8F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane] has been well established and used for the differential diagnosis of atypical parkinsonian disorders. Recently, combined positron emission tomography (PET)/magnetic resonance (MR) was proposed as a viable alternative to PET/computed tomography (CT). The aim of this study was to compare the performances of conventional {sup 18}F-FP-CIT brain PET/CT and simultaneous PET/MR by visual inspection and quantitative analysis. Fifteen consecutive patients clinically suspected of having Parkinson's disease were recruited for the study.{sup 18}F-FP-CIT PET was performed during PET/CT and PET/MR. PET/CT image acquisition was started 90 min after intravenous injection of {sup 18}F-FP-CIT and then PET/MR images were acquired. Dopamine transporter (DAT) density in bilateral striatal subregions was assessed visually. Quantitative analyses were performed on bilateral striatal volumes of interest (VOIs) using average standardized uptake values (SUVmeans). Intraclass correlation coefficients (ICCs) and their 95 % confidence intervals (CIs) were assessed to compare PET/CT and PET/MR data. Bland-Altman plots were drawn to perform method-comparisons. All subjects showed a preferential decrease in DAT binding in the posterior putamen (PP), with relative sparing of the ventral putamen (VP). Bilateral striatal subregional binding ratio (BR) determined PET/CT and PET/MR demonstrated close interequipment correspondence (BRright caudate - ICC, 0.944; 95 % CI, 0.835-0.981, BRleft caudate - ICC, 0.917; 95 % CI, 0.753-0.972, BRright putamen - ICC, 0.976; 95 % CI, 0.929-0.992 and BRleft putamen - ICC, 0.970; 95 % CI, 0.911-0.990, respectively), and Bland-Altman plots showed interequipment agreement between the two modalities. It is known that MR provides more information about anatomical changes associated with brain diseases and to enable the anatomical allocations of

Radiopharmacological evaluation of 18F-labeled phosphatidylserine-binding peptides for molecular imaging of apoptosis

International Nuclear Information System (INIS)

Wuest, Melinda; Perreault, Amanda; Kapty, Janice; Richter, Susan; Foerster, Christian; Bergman, Cody; Way, Jenilee; Mercer, John; Wuest, Frank

2015-01-01

Introduction: Radiolabeled phosphatidylserine (PS)-binding peptides represent an innovative strategy for molecular imaging of apoptosis with positron emission tomography (PET). The goal of this study was the radiopharmacological evaluation of radiolabeled peptides for their binding to PS on apoptotic cancer cells, involving metabolic stability, cellular uptake, biodistribution, and dynamic PET imaging experiments. Methods: Binding of peptides LIKKPF, PGDLSR, FBz-LIKKPF, FBz-PGDLSR, FBAM-CLIKKPF and FBAM-CPGDLSR to PS was analyzed in a newly developed radiometric binding assay using 64 Cu-labeled wild-type annexin-V as radiotracer. Radiolabeling of most potent peptides with fluorine-18 was carried out with thiol-selective prosthetic group [ 18 F]FBAM to give [ 18 F]FBAM-CLIKKPF and [ 18 F]FBAM-CPGDLSR. [ 18 F]FBAM-labeled peptides were studied in camptothecin-induced apoptotic human T lymphocyte Jurkat cells, and in a murine EL4 tumor model of apoptosis using dynamic PET imaging and biodistribution. Results: Peptides LIKKPF and PGDLSR inhibited binding of 64 Cu-labeled annexin-V to immobilized PS in the millimolar range (IC 50 10–15 mM) compared to annexin-V (45 nM). Introduction of FBAM prosthetic group slightly increased inhibitory potencies (FBAM-CLIKKPF: IC 50 = 1 mM; FBAM-CPGDLSR: IC 50 = 6 mM). Radiolabeling succeeded in good radiochemical yields of 50–54% using a chemoselective alkylation reaction of peptides CLIKKPF and CPGDLSR with [ 18 F]FBAM. In vivo metabolic stability studies in mice revealed 40–60% of intact peptides at 5 min p.i. decreasing to 25% for [ 18 F]FBAM-CLIKKPF and less than 5% for [ 18 F]FBAM-CPGDLSR at 15 min p.i.. Cell binding of [ 18 F]FBAM-CLIKKPF in drug-treated Jurkat cells was significantly higher compared to untreated cells, but this was not observed for [ 18 F]FBAM-CPGDLSR. Dynamic PET imaging experiments showed that baseline uptake of [ 18 F]FBAM-CLIKKPF in EL4 tumors was higher (SUV 5min 0.46, SUV 60min 0.13) compared to

Skin Manifestation of Unsuspecting Prostate Cancer Detected by {sup 18}F-FDG PET/CT Performed To Assess Underlying Multiple Myeloma

Energy Technology Data Exchange (ETDEWEB)

AbAziz, Aini; Mahaletchumy, Thanuja; Chung, Junekey [Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur (Malaysia)

2013-12-15

Skin metastases from either prostate adenocarcinoma or multiple myeloma rarely occur. We report the case of a 73-year-old man with multiple myeloma who presented with multiple subcutaneous nodules 3 years after his initial diagnosis. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging was suggestive of a concomitant second primary from the prostate. This case highlights not only a rare initial manifestation of prostate cancer, but also the role of 18F-FDG-PET/CT in detecting a clinically unsuspected second malignancy. It potentially corroborates the possible association of both diseases, as has been reported before.

Evaluation of Fluorine-18-Labeled α1(I-N-Telopeptide Analogs as Substrate-Based Radiotracers for PET Imaging of Melanoma-Associated Lysyl Oxidase

Directory of Open Access Journals (Sweden)

Manuela Kuchar

2018-04-01

Full Text Available Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB as prosthetic reagent. With regards to potential crosslinking to tumor-associated collagen in vivo, their interaction with triple-helical type I collagen was studied by SPR. A mouse model of human melanoma was established on the basis of the A375 cell line, for which the expression of the oncologically relevant lysyl oxidase isoforms LOX and LOXL2 was demonstrated in Western blot and immunohistochemical experiments. The radiopharmacological profiles of the peptidic radiotracers were evaluated in normal rats and A375 melanoma-bearing mice by ex vivo metabolite analysis, whole-body biodistribution studies and dynamic PET imaging. Out of three 18F-labeled telopeptide analogs, the one with the most favorable substrate properties has shown favorable tumor uptake and tumor-to-muscle ratio. Lysyl oxidase-mediated tumor uptake was proven by pharmacological inhibition using β-aminopropionitrile and by employing negative-control analogs of impeded or abolished targeting capability. The latter were obtained by substituting the lysine residue by ornithine and norleucine, respectively. Comparing the tumor uptake of the lysine-containing peptide with that of the non-functional analogs indicate the feasibility of lysyl oxidase imaging in melanoma using substrate-based radiotracers.

Evaluation of Fluorine-18-Labeled α1(I)-N-Telopeptide Analogs as Substrate-Based Radiotracers for PET Imaging of Melanoma-Associated Lysyl Oxidase.

Science.gov (United States)

Kuchar, Manuela; Neuber, Christin; Belter, Birgit; Bergmann, Ralf; Lenk, Jens; Wodtke, Robert; Kniess, Torsten; Steinbach, Jörg; Pietzsch, Jens; Löser, Reik

2018-01-01

Accumulating evidence suggests an unequivocal role of lysyl oxidases as key players of tumor progression and metastasis, which renders this enzyme family highly attractive for targeted non-invasive functional imaging of tumors. Considering their function in matrix remodeling, malignant melanoma appears as particularly interesting neoplasia in this respect. For the development of radiotracers that enable PET imaging of the melanoma-associated lysyl oxidase activity, substrates derived from the type I collagen α1 N-telopeptide were labeled with fluorine-18 using N -succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB) as prosthetic reagent. With regards to potential crosslinking to tumor-associated collagen in vivo , their interaction with triple-helical type I collagen was studied by SPR. A mouse model of human melanoma was established on the basis of the A375 cell line, for which the expression of the oncologically relevant lysyl oxidase isoforms LOX and LOXL2 was demonstrated in Western blot and immunohistochemical experiments. The radiopharmacological profiles of the peptidic radiotracers were evaluated in normal rats and A375 melanoma-bearing mice by ex vivo metabolite analysis, whole-body biodistribution studies and dynamic PET imaging. Out of three 18 F-labeled telopeptide analogs, the one with the most favorable substrate properties has shown favorable tumor uptake and tumor-to-muscle ratio. Lysyl oxidase-mediated tumor uptake was proven by pharmacological inhibition using β-aminopropionitrile and by employing negative-control analogs of impeded or abolished targeting capability. The latter were obtained by substituting the lysine residue by ornithine and norleucine, respectively. Comparing the tumor uptake of the lysine-containing peptide with that of the non-functional analogs indicate the feasibility of lysyl oxidase imaging in melanoma using substrate-based radiotracers.

Synthesis and biological evaluation in rat and cat of [18F]12ST05 as a potential 5-HT6 PET radioligand

International Nuclear Information System (INIS)

Tang, Sandrine; Verdurand, Mathieu; Joseph, Benoit; Lemoine, Laetitia; Daoust, Alexia; Billard, Thierry; Fournet, Guy; Le Bars, Didier; Zimmer, Luc

2007-01-01

Introduction: 5-hydroxytryptamine (5-HT) 6 receptors represent one of the more recently discovered serotoninergic receptor family. However, no 5-HT 6 positron emission tomography (PET) radiotracer is currently used in clinical imaging studies. The purpose of this study was to propose the first fluorinated PET radiotracer for this brain receptor. Methods: A new compound presenting in vitro high affinity towards the serotoninergic 5-HT 6 receptor, N-[2-(1-[(4-fluorophenyl)sulfonyl]-1H-indol-4-yloxy)ethyl] -N,N-dimethylamine, was labelled with fluorine 18 via a nitro-/fluoronucleophilic substitution. Biological evaluations included (i) in vitro and ex vivo autoradiographies in rat brain and (ii) a PET scan on anaesthetized cat. Results and Conclusion: Although the radioligand showed excellent brain penetration, it did not reveal any specific binding to the 5-HT 6 receptors indicating that this radiotracer is not suitable for mapping 5-HT 6 receptors using PET

Coronary fluorine-18-sodium fluoride uptake is increased in healthy adults with an unfavorable cardiovascular risk profile

DEFF Research Database (Denmark)

Blomberg, Björn A; Thomassen, Anders; de Jong, Pim A

2017-01-01

OBJECTIVE: Coronary artery fluorine-18-sodium fluoride (F-NaF) uptake reflects coronary artery calcification metabolism and is considered to be an early prognostic marker of coronary heart disease. This study evaluated the relationship between coronary artery F-NaF uptake and cardiovascular risk ...... adults at low cardiovascular risk and that an unfavorable cardiovascular risk profile is associated with a marked increase in coronary artery F-NaF uptake.......OBJECTIVE: Coronary artery fluorine-18-sodium fluoride (F-NaF) uptake reflects coronary artery calcification metabolism and is considered to be an early prognostic marker of coronary heart disease. This study evaluated the relationship between coronary artery F-NaF uptake and cardiovascular risk...... in healthy adults at low cardiovascular risk. PARTICIPANTS AND METHODS: Study participants underwent blood pressure measurements, blood analyses, and coronary artery F-NaF PET/CT imaging. In addition, the 10-year risk for the development of cardiovascular disease, on the basis of the Framingham Risk Score...

Diagnostic accuracy of 18F-FDG-PET and PET/CT in the differential diagnosis between malignant and benign pleural lesions: a systematic review and meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Bertagna, Francesco; Prior, John O; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

H18F: production and use in aromatic fluorinations via triazenes

International Nuclear Information System (INIS)

Kilbourn, M.R.; Saji, H.; Welch, M.J.

1982-01-01

Studies with the triazene method of radiofluorination are presented, including the production and use of anhydrous H 18 F, investigations into the best reaction conditions, and studies of the stability and purification of the 18 F-labeled products. Despite problems with low yields, the use of triazenes in the prepartion of fluorine-18 labeled receptor ligands remains a sound synthetic approach, and the only one available for no-carrier-added syntheses. However, it appears that the fluorine-18 fluorination yields are much higher with simpler triazenes. For this reason, synthetic efforts are now focused on the preparation of 18 F-spiroperidol by a convergent synthesis

Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

International Nuclear Information System (INIS)

Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H.; Ted Treves, S.; Packard, Alan B.

2010-01-01

There is considerable interest in developing an 18 F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99m Tc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18 F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99m Tc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18 F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18 F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2'-[ 18 F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [ 18 F]fluoroethyltosylate in acetonitrile at 165 deg. C for 30 min using [ 18 F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K 2 CO 3 , and [ 18 F]NaF in acetonitrile for 10 min at 90 deg. C. The product was purified by semi-preparative HPLC to produce the 2'-[ 18 F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min.

Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

Science.gov (United States)

Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H; Treves, S. Ted; Packard, Alan B.

2009-01-01

There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2′-[18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [18F]fluoroethyltosylate in acetonitrile at 165°C for 30 min.using [18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [18F]NaF in acetonitrile for 10 min. at 90°C. The product was purified by semi-preparative HPLC to produce the 2′-[18F]-fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. PMID:19783150

Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.

Science.gov (United States)

Ni, Dalong; Jiang, Dawei; Ehlerding, Emily B; Huang, Peng; Cai, Weibo

2018-03-20

As one of the most biocompatible and well-tolerated inorganic nanomaterials, silica-based nanoparticles (SiNPs) have received extensive attention over the last several decades. Recently, positron emission tomography (PET) imaging of radiolabeled SiNPs has provided a highly sensitive, noninvasive, and quantitative readout of the organ/tissue distribution, pharmacokinetics, and tumor targeting efficiency in vivo, which can greatly expedite the clinical translation of these promising NPs. Encouraged by the successful PET imaging of patients with metastatic melanoma using 124 I-labeled ultrasmall SiNPs (known as Cornell dots or C dots) and their approval as an Investigational New Drug (IND) by the United States Food and Drug Administration, different radioisotopes ( 64 Cu, 89 Zr, 18 F, 68 Ga, 124 I, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense silica (dSiO 2 ), mesoporous silica (MSN), biodegradable mesoporous silica (bMSN), and hollow mesoporous silica nanoparticles (HMSN). With in-depth knowledge of coordination chemistry, abundant silanol groups (-Si-O-) on the silica surface or inside mesoporous channels not only can be directly used for chelator-free radiolabeling but also can be readily modified with the right chelators for chelator-based labeling. However, integrating these labeling strategies for constructing stably radiolabeled SiNPs with high efficiency has proven difficult because of the complexity of the involved key parameters, such as the choice of radioisotopes and chelators, nanostructures, and radiolabeling strategy. In this Account, we present an overview of recent progress in the development of radiolabeled SiNPs for cancer theranostics in the hope of speeding up their biomedical applications and potential translation into the clinic. We first introduce the basic principles and mechanisms for radiolabeling SiNPs via coordination chemistry, including general rules of selecting proper

Evaluation of the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

International Nuclear Information System (INIS)

Wetter, Axel; Lipponer, Christine; Nensa, Felix; Altenbernd, Jens-Christian; Schlosser, Thomas; Lauenstein, Thomas; Heusch, Philipp; Ruebben, Herbert; Bockisch, Andreas; Poeppel, Thorsten; Nagarajah, James

2014-01-01

The aim of this study was to evaluate the positron emission tomography (PET) component of [ 18 F]choline PET/MRI and compare it with the PET component of [ 18 F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer. Thirty-six patients were examined with simultaneous [ 18 F]choline PET/MRI following combined [ 18 F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV max and SUV mean ) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV max and SUV mean was tested using Pearson's product-moment correlation and Bland-Altman analysis. All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV max and SUV mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p max of PET/CT and PET/MRI (R = 0.86, p mean of PET/CT and PET/MRI (R = 0.81, p max of PET/CT vs PET/MRI and -1.12 to +2.23 between SUV mean of PET/CT vs PET/MRI. PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV max and SUV mean was found. Both SUV max and SUV mean were significantly lower in [ 18 F]choline PET/MRI than in [ 18 F]choline PET/CT. Differences of SUV max and SUV mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [ 18 F]choline between the subsequent examinations and in the respective organ systems have to be taken into account. (orig.)

Rapid synthesis of maleimide functionalized fluorine-18 labeled prosthetic group using "radio-fluorination on the Sep-Pak" method.

Science.gov (United States)

Basuli, Falguni; Zhang, Xiang; Jagoda, Elaine M; Choyke, Peter L; Swenson, Rolf E

2018-03-25

Following our recently published fluorine-18 labeling method, "Radio-fluorination on the Sep-Pak", we have successfully synthesized 6-[ 18 F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO 3 ). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [ 18 F]fluoronicotinaldehyde ([ 18 F]5) was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled maleimide functionalized prosthetic group, 6-[ 18 F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[ 18 F]FPyMHO ([ 18 F]6). The current Sep-Pak method not only improves the overall radiochemical yield (50 ± 9%, decay-corrected, n = 9) but also significantly reduces the synthesis time (from 60-90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar prosthetic groups. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Diagnostic Performance of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in the Postchemotherapy Management of Patients with Seminoma: Systematic Review and Meta-Analysis

Directory of Open Access Journals (Sweden)

Giorgio Treglia

2014-01-01

Full Text Available Objective. To meta-analyze published data about the diagnostic performance of fluorine-18-Fluorodeoxyglucose (18F-FDG positron emission tomography (PET and PET/computed tomography (PET/CT in the postchemotherapy management of patients with seminoma. Methods. A comprehensive literature search of studies published through January 2014 on this topic was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity and specificity, positive and negative predictive values (PPV and NPV, accuracy, and area under the summary ROC curve (AUC of 18F-FDG-PET or PET/CT on a per examination-based analysis were calculated. Subgroup analyses considering the size of residual/recurrent lesions were carried out. Results. Nine studies including 375 scans were selected. The pooled analysis provided the following results: sensitivity 78% (95% confidence interval (95% CI: 67–87%, specificity 86% (95% CI: 81–89%, PPV 58% (95% CI: 48–68%, NPV 94% (95% CI: 90–96%, and accuracy 84% (95% CI: 80–88%. The AUC was 0.90. A better diagnostic accuracy of 18F-FDG-PET or PET/CT in evaluating residual/recurrent lesions >3 cm compared to those <3 cm was found. Conclusions. 18F-FDG-PET and PET/CT were demonstrated to be accurate imaging methods in the postchemotherapy management of patients with seminoma; nevertheless possible sources of false-negative and false-positive results should be considered. The literature focusing on this setting still remains limited and cost-effectiveness analyses are warranted.

Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma

International Nuclear Information System (INIS)

Cremerius, U.; Zimny, M.; Bares, R.; Buell, U.; Fabry, U.; Osieka, R.; Neuerburg, J.

2001-01-01

Aim: To evaluate the prognostic significance of positron emission tomography (PET) using fluorine-18-[2]-fluoro-2-deoxyglucose (FDG) in patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) compared to conventional restaging (CRS). Methods: Fifty-six patients with either HD (n = 22), high-grade NHL (n = 26) or centrocytic-centroblastic NHL (n = 8) were included. PET was performed in 41 patients for treatment reevaluation up to three months after therapy and in patients with persisting residual masses (n = 10) or suspected relapse (n = 5) four to twelve months after treatment. The scans were evaluated qualitatively and quantitatively using standardised uptake values (SUV). Progression-free survival (PFS) was estimated to assess the prognostic value of FDG PET and clinical follow-up was taken as gold standard. Results: PET was positive in nineteen of 41 patients studied for treatment reevaluation. Progression was observed after a median interval of two months (range 0-15) in sixteen of 19 patients after a positive PET scan and in three of 22 patients after a negative scan (p 11.35 of lymphoma lesions was associated with poorer PFS than SUV [de

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

Science.gov (United States)

Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

2012-06-01

Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P measurements with acceptable radiation exposure. Although further modifications to improve the performance of (18)F-NOS are needed, these data show the feasibility of PET of iNOS in the heart and other tissues.

Preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes

OpenAIRE

Gheysens, Olivier; Akurathi, Vamsidhar; Chekol, Rufael; Dresselaers, Tom; Celen, Sofie; Koole, Michel; Dauwe, Dieter; Cleynhens, Bernard J; Claus, Piet; Janssens, Stefan; Verbruggen, Alfons M; Nuyts, Johan; Himmelreich, Uwe; Bormans, Guy M

2013-01-01

Background To date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron ...

Appropriateness criteria of FDG PET/CT in oncology

International Nuclear Information System (INIS)

Agrawal, Archi; Rangarajan, Venkatesh

2015-01-01

18 Fluorine-2-fluoro-2-Deoxy-d-glucose ( 18 F-FDG) positron emission tomography/computerized tomography (PET/CT) is a well-established functional imaging method widely used in oncology. In this article, we have incorporated the various indications for 18 FDG PET/CT in oncology based on available evidence and current guidelines. Growing body of evidence for use of 18 FDG PET/CT in select tumors is also discussed. This article attempts to give the reader an overview of the appropriateness of using 18 F-FDG PET/CT in various malignancies

Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent.

Science.gov (United States)

Huang, Shun; Han, Yanjiang; Chen, Min; Hu, Kongzhen; Qi, Yongshuai; Sun, Penghui; Wang, Men; Wu, Hubing; Li, Guiping; Wang, Quanshi; Du, Zhiyun; Zhang, Kun; Zhao, Suqing; Zheng, Xi

2018-04-01

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2- 18 F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine ( 18 F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18 F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18 F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18 F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18 F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18 F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18 F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

18F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis.

International Nuclear Information System (INIS)

Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C.

2008-01-01

Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68 Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ( 18 F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18 F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18 F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18 F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18 F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection

Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

Energy Technology Data Exchange (ETDEWEB)

Heinrich, Tobias K.; Gottumukkala, Vijay [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Snay, Erin; Dunning, Patricia [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Fahey, Frederic H.; Ted Treves, S. [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Packard, Alan B. [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States)], E-mail: alan.packard@childrens.harvard.edu

2010-01-15

There is considerable interest in developing an {sup 18}F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with {sup 99m}Tc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an {sup 18}F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like {sup 99m}Tc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether {sup 18}F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the {sup 18}F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2'-[{sup 18}F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [{sup 18}F]fluoroethyltosylate in acetonitrile at 165 deg. C for 30 min using [{sup 18}F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K{sub 2}CO{sub 3}, and [{sup 18}F]NaF in acetonitrile for 10 min at 90 deg. C. The product was purified by semi-preparative HPLC to produce the 2'-[{sup 18}F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/{mu}mol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min.

Fluorine-18 heart dosimetry in myocardial perfusion imaging

Energy Technology Data Exchange (ETDEWEB)

Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R., E-mail: janine.toledo@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pós-Graduação em Ciências e Técnicas Nucleares

2017-07-01

This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

Fluorine-18 heart dosimetry in myocardial perfusion imaging

International Nuclear Information System (INIS)

Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R.

2017-01-01

This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

18F-Fluoroacetate - A longer lived acetate analogue for oncology studies with PET

International Nuclear Information System (INIS)

Khezami, Arbia; Ulrich, Eva; Matthies, Alexander; Ezziddin, Samer; Bender, Hans; Biersack, Hans-Juergen; Guhlke, Stefan

2004-01-01

Full text: Aim: 18 F-Fluoroacetate ( 18 Fac) can be considered as a fluoro analogue of 11C-acetate. Thus it may also be useful for oncologic PET studies. Like acetate, fluoroacetate is a substrate of the citric acid cycle, however in contrast to acetate it is an inhibitor of the enzyme Aconitase and thus no further metabolization of fluoroacetate occurs. The aim of this study was the in-vivo evaluation of this tracer with respect to tumor uptake in prostate carcinoma bearing nude mice as well as biodistribution and kinetics. Methods: The synthesis of 18 F-fluoroacetate was performed by using benzyl bromoacetate as precursor. The fluorinated ester was separated by HPLC, followed by basic hydrolysis and purification by use of anion exchange SEP-Pak chromatography. The formulation was performed by rinsing with water and subsequent elution of 18 Fac with sterile PBS-buffer and final sterile filtration. For the biodistribution studies, 3 groups of nude mice were inoculated with the prostate carcinoma cell lines PC3, DU-145 and LnCAP. After tumor growth, the animals were injected with 37-370 KBq of 18 Fac and bio-distributions performed at different times post injection. Results: The rcy of the substitution step was usually > 90%. The HPLC separation of the fluorinated ester and the precursor was performed on a C-18 column. The high UV-absorbance of the benzyl ester allows the determination of the specific activity of the tracer which was always lower than detection limits. Further, the injected animals did not show any signs of intoxication. The biodistribution studies revealed a primary biliary excretion. Regardless which cell line was used, accumulation of 18 Fac in tumor sites was well visible by PET-CT. Tumor to blood ratios increased with time. Conclusion: The synthesis of 18 Fac is straight forward and high radiochemical yields are typically obtained. The high specific activity of 18 F-fluoride allows injections of 18 Fac far below toxic concentrations. In nude

Presurgical evaluation of pediatric epilepsy patients prior to hemispherotomy: the prognostic value of 18F-FDG PET.

Science.gov (United States)

Traub-Weidinger, Tatjana; Weidinger, Philip; Gröppel, Gundrun; Karanikas, Georgios; Wadsak, Wolfgang; Kasprian, Gregor; Dorfer, Christian; Dressler, Anastasia; Muehlebner, Angelika; Hacker, Marcus; Czech, Thomas; Feucht, Martha

2016-12-01

OBJECTIVE The objective of this study was to investigate whether fluorine-18 fluorodeoxyglucose PET ( 18 F-FDG PET) can help to predict seizure outcome after hemispherotomy and therefore may be useful in decision making and patient selection. METHODS Children and adolescents less than 18 years of age who underwent 18 F-FDG PET studies during presurgical evaluation prior to hemispherotomy and had follow-up data of at least 12 months after surgery were included. Seizure outcome was classified according to the recommendations of the International League Against Epilepsy. PET data were reevaluated by two specialists in nuclear medicine blinded to clinical data and to MRI. MRI studies were also reinterpreted visually by an experienced neuroradiologist blinded to clinical data and PET findings. RESULTS Thirty-five patients (17 girls) with a median age of 5 years (range 0.4-17.8 years) were evaluable. Of the 35 patients, 91.4% were seizure free after surgery, including 100% of those with unilateral 18 F-FDG-PET hypometabolism compared with only 75% of those with bilateral hypometabolism. With respect to MRI, seizure freedom after surgery was observed in 96.4% of the patients with unilateral lesions compared with only 71.4% in those with bilateral MRI lesions. The best seizure outcomes were noted in patients with unilateral findings in both PET and MRI (100% seizure freedom) whereas only 50% of those with bilateral findings in both imaging techniques were seizure free. Furthermore, 100% of the patients with unilateral PET hypometabolism and bilateral MRI findings were also seizure free, but only 87.5% of those with bilateral PET hypometabolism and unilateral MRI findings. CONCLUSIONS According to these results, candidate selection for hemispherotomy can be optimized by the use of 18 F-FDG PET as part of a multimodal presurgical evaluation program, especially in patients with inconsistent (bilateral) MRI findings.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

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Gruenwald, F [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Schomburg, A [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Bender, H [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Klemm, E [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Menzel, C [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Bultmann, T [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Palmedo, H [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Ruhlmann, J [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Kozak, B [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Biersack, H J [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany)

1996-03-01

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with {sup 131}I) and a negative FDG PET, in four cases {sup 131}I-negative lymph node metastases were detectable with PET. Even in the patients with concordant ``staging``, differences between {sup 131}I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of {sup 131}I-positive/FDG-negative, {sup 131}I-negative/FDG-positive and {sup 131}I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours {sup 131}I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS. (orig.). With 3 figs., 2 tabs.

Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: a systematic review and a meta-analysis.

Science.gov (United States)

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Prior, John O; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

Energy Technology Data Exchange (ETDEWEB)

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

Energy Technology Data Exchange (ETDEWEB)

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

International Nuclear Information System (INIS)

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks

[{sup 18}F]FDG PET/CT outperforms [{sup 18}F]FDG PET/MRI in differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Burg, Matthias Christian; Allkemper, Thomas [University Hospital Muenster, Department of Clinical Radiology, Muenster (Germany); Schaefers, Michael [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Westfaelische Wilhelms University Muenster, European Institute for Molecular Imaging, Muenster (Germany)

2016-02-15

To evaluate the diagnostic potential of PET/MRI with [{sup 18}F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [{sup 18}F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [{sup 18}F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [{sup 18}F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [{sup 18}F]FDG PET/MRI was inferior to low-dose [{sup 18}F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [{sup 18}F]FDG PET/MRI was equal to contrast-enhanced neck [{sup 18}F]FDG PET/CT. Therefore, [{sup 18}F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast

Pilot study utilizing Fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography for glycolytic phenotyping of canine mast cell tumors.

Science.gov (United States)

Griffin, Lynn R; Thamm, Doug H; Selmic, Laura E; Ehrhart, E J; Randall, Elissa

2018-03-23

The goal of this prospective pilot study was to use naturally occurring canine mast cell tumors of various grades and stages as a model for attempting to determine how glucose uptake and markers of biologic behavior are correlated. It was hypothesized that enhanced glucose uptake, as measured by 2-[fluorine-18]fluoro-d-glucose-positron emission tomography/computed tomography (F18 FDG PET-CT), would correlate with histologic grade. Dogs were recruited for this study from a population referred for treatment of cytologically or histologically confirmed mast cell tumors. Patients were staged utilizing standard of care methods (abdominal ultrasound and three view thoracic radiographs), followed by a whole body F18 FDG PET-CT. Results of the F18 FDG PET-CT were analyzed for possible metastasis and standard uptake value maximum (SUV max ) of identified lesions. Incisional or excisional biopsies of the accessible mast cell tumors were obtained and histology performed. Results were then analyzed to look for a possible correlation between the grade of mast cell tumors and SUV max . A total of nine animals were included in the sample. Findings indicated that there was a correlation between grade of mast cell tumors and SUV max as determined by F18 FDG PET-CT (p-value = 0.073, significance ≤ 0.1). Based on the limited power of this study, it is felt that further research to examine the relationship between glucose utilization and biologic aggressiveness in canine mast cell tumors is warranted. This study was unable to show that F18 FDG PET-CT was a better staging tool than standard of care methods. © 2018 American College of Veterinary Radiology.

Lower maximum standardized uptake value of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography imaging in pancreatic ductal adenocarcinoma patients with diabetes.

Science.gov (United States)

Chung, Kwang Hyun; Park, Joo Kyung; Lee, Sang Hyub; Hwang, Dae Wook; Cho, Jai Young; Yoon, Yoo-Seok; Han, Ho-Seong; Hwang, Jin-Hyeok

2015-04-01

The effects of diabetes mellitus (DM) on sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography ((18)F-FDG PET/CT) for diagnosing pancreatic ductal adenocarcinomas (PDACs) is not well known. This study was aimed to evaluate the effects of DM on the validity of (18)F-FDG PET/CT in PDAC. A total of 173 patients with PDACs who underwent (18)F-FDG PET/CT were enrolled (75 in the DM group and 98 in the non-DM group). The maximum standardized uptake values (SUVsmax) were compared. The mean SUVmax was significantly lower in the DM group than in the non-DM group (4.403 vs 5.998, P = .001). The sensitivity of SUVmax (cut-off value 4.0) was significantly lower in the DM group than in the non-DM group (49.3% vs 75.5%, P < .001) and also lower in normoglycemic DM patients (n = 24) than in non-DM patients (54.2% vs 75.5%, P = .038). DM contributes to a lower SUVmax of (18)F-FDG PET/CT in patients with PDACs. Copyright © 2015 Elsevier Inc. All rights reserved.

Thoracic staging in lung cancer: prospective comparison of 18F-FDG PET/MR imaging and 18F-FDG PET/CT.

Science.gov (United States)

Heusch, Philipp; Buchbender, Christian; Köhler, Jens; Nensa, Felix; Gauler, Thomas; Gomez, Benedikt; Reis, Henning; Stamatis, Georgios; Kühl, Hilmar; Hartung, Verena; Heusner, Till A

2014-03-01

Therapeutic decisions in non-small cell lung cancer (NSCLC) patients depend on the tumor stage. PET/CT with (18)F-FDG is widely accepted as the diagnostic standard of care. The purpose of this study was to compare a dedicated pulmonary (18)F-FDG PET/MR imaging protocol with (18)F-FDG PET/CT for primary and locoregional lymph node staging in NSCLC patients using histopathology as the reference. Twenty-two patients (12 men, 10 women; mean age ± SD, 65.1 ± 9.1 y) with histopathologically confirmed NSCLC underwent (18)F-FDG PET/CT, followed by (18)F-FDG PET/MR imaging, including a dedicated pulmonary MR imaging protocol. T and N staging according to the seventh edition of the American Joint Committee on Cancer staging manual was performed by 2 readers in separate sessions for (18)F-FDG PET/CT and PET/MR imaging, respectively. Results from histopathology were used as the standard of reference. The mean and maximum standardized uptake value (SUV(mean) and SUV(max), respectively) and maximum diameter of the primary tumor was measured and compared in (18)F-FDG PET/CT and PET/MR imaging. PET/MR imaging and (18)F-FDG PET/CT agreed on T stages in 16 of 16 of patients (100%). All patients were correctly staged by (18)F-FDG PET/CT and PET/MR (100%), compared with histopathology. There was no statistically significant difference between (18)F-FDG PET/CT and (18)F-FDG PET/MR imaging for lymph node metastases detection (P = 0.48). For definition of thoracic N stages, PET/MR imaging and (18)F-FDG PET/CT were concordant in 20 of 22 patients (91%). PET/MR imaging determined the N stage correctly in 20 of 22 patients (91%). (18)F-FDG PET/CT determined the N stage correctly in 18 of 22 patients (82%). The mean differences for SUV(mean) and SUV(max) of NSCLC in (18)F-FDG PET/MR imaging and (18)F-FDG PET/CT were 0.21 and -5.06. These differences were not statistically significant (P > 0.05). The SUV(mean) and SUV(max) measurements derived from (18)F-FDG PET/CT and (18)F-FDG PET

Fluorinase: a tool for the synthesis of ¹⁸F-labeled sugars and nucleosides for PET.

Science.gov (United States)

Onega, Mayca; Winkler, Margit; O'Hagan, David

2009-08-01

There is an increasing interest in the preparation of (18)F-labeled radiopharmaceuticals with potential applications in PET for medicinal imaging. Appropriate synthetic methods require a quick and efficient route in which to incorporate the (18)F into a ligand, due to the relatively short half-life of the (18)F isotope. Enzymatic methods are rare in this area; however, the discovery of a fluorinating enzyme from Streptomyces cattleya (EC 2.5.1.63) has opened up the possibility of the enzymatic synthesis and formation of C-(18)F bonds from the [(18)F]fluoride ion. In this article, the development of enzymatic preparations of (18)F-labeled sugars and nucleosides as potential radiotracers using the fluorinase from S. cattleya for PET applications is reviewed. Enzymatic reactions are not traditional in PET synthesis, but this enzyme has some attractive features. The enzyme is available in an overexpressed form from Escherichia coli and it is relatively stable and can be easily purified and manipulated. Most notably, it utilizes [(18)F] fluoride, the form of the isotope normally generated by the cyclotron and usually in very high specific radioactivity. The disadvantage with the enzyme is that it is substrate specific; however, when the fluorinase is used in combination biotransformations with a second or third enzyme, then a range of radiolabeled nucleosides and ribose sugars can be prepared. The fluorinase enzyme has emerged as a curiosity from biosynthesis studies, but it now has some potential as a new catalyst for (18)F incorporation for PET syntheses. The focus is now on delivering a user-friendly catalyst to the PET synthesis community and establishing a clinical role for some of the (18)F-labeled molecules available using this technology.

Synthesis and biological evaluation in rat and cat of [{sup 18}F]12ST05 as a potential 5-HT{sub 6} PET radioligand

Energy Technology Data Exchange (ETDEWEB)

Tang, Sandrine [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Verdurand, Mathieu [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Joseph, Benoit [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Lemoine, Laetitia [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Daoust, Alexia [CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Billard, Thierry; Fournet, Guy [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Le Bars, Didier [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Zimmer, Luc [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France)], E-mail: zimmer@univ-lyon1.fr

2007-11-15

Introduction: 5-hydroxytryptamine (5-HT){sub 6} receptors represent one of the more recently discovered serotoninergic receptor family. However, no 5-HT{sub 6} positron emission tomography (PET) radiotracer is currently used in clinical imaging studies. The purpose of this study was to propose the first fluorinated PET radiotracer for this brain receptor. Methods: A new compound presenting in vitro high affinity towards the serotoninergic 5-HT{sub 6} receptor, N-[2-(1-[(4-fluorophenyl)sulfonyl]-1H-indol-4-yloxy)ethyl] -N,N-dimethylamine, was labelled with fluorine 18 via a nitro-/fluoronucleophilic substitution. Biological evaluations included (i) in vitro and ex vivo autoradiographies in rat brain and (ii) a PET scan on anaesthetized cat. Results and Conclusion: Although the radioligand showed excellent brain penetration, it did not reveal any specific binding to the 5-HT{sub 6} receptors indicating that this radiotracer is not suitable for mapping 5-HT{sub 6} receptors using PET.

18 F-Labeling of Sensitive Biomolecules for Positron Emission Tomography.

Science.gov (United States)

Krishnan, Hema S; Ma, Longle; Vasdev, Neil; Liang, Steven H

2017-11-07

Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via "direct" or "indirect" bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18 F-labeling of biomolecules in PET imaging research studies are highlighted. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Imaging of large vessel vasculitis with 18FDG PET: illusion or reality? A critical review of the literature data

International Nuclear Information System (INIS)

Belhocine, Tarik; Vandevivere, Johan; Blockmans, Daniel; Hustinx, Roland; Mortelmans, Luc

2003-01-01

Fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of 18 FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the 18 FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging. (orig.)

18F-FDG-PET in the follow-up of thyroid cancer

International Nuclear Information System (INIS)

Lind, P.; Kresnik, E.; Kumnig, G.; Gallowitsch, H.-J.; Igerc, I.; Matschnig, S.; Gomez, I.

2003-01-01

Differentiated thyroid cancer is a rare tumor with an incidence of 4-9/100000/year. For preoperative assessment of thyroid nodules, ultrasonography (US) and US-guided fine needle aspiration biopsy are the methods of choice to detect thyroid cancer. The value of preoperative fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) in differentiating malignant from benign nodules, especially in cases of follicular proliferation, has not yet been evaluated. After thyroidectomy and radioiodine remnant ablation, several methods are used to follow patients with differentiated thyroid cancer, including serum thyroglobulin, ultrasonography of the neck, iodine-131 ( 131 I) whole body scintigraphy (WBS) and scintigraphy with nonspecific tracers such as technetium-99 m ( 99m Tc) Tetrofosmin or Sestamibi. Whereas the specificity of 131 I-WBS is high, sensitivity is low, especially if one takes into account that only two-thirds of recurrences or metastases store iodine. With the introduction of 18 F-FDG in oncology, it is also used for the detection of local recurrences and metastases of differentiated thyroid cancer. Elevated thyroglobulin but negative 131 I-WBS belongs to the 1a indications for 18 F-FDG-PET in oncology according to the German Consensus Conference 2000. The sensitivity for detecting 131 I-negative metastases with 18 F-FDG-PET can be increased by elevated thyroid-stimulating hormone (TSH) after withdrawal of thyroid hormone therapy or after intra-muscular injection of recombinant TSH. Most of the 131 I-negative metastases demonstrate 18 F-FDG uptake, which represents rapid tumor growth and poor differentiation, whereas most of the 131 I-positive metastases are 18 F-FDG negative. The combination of 131 I-WBS and 18 F-FDG-PET leads to an increase in the detection rate to more than 90-95 % in cases of elevated thyroglobulin, because well- and less-differentiated cancer cells may be present in one patient. In rare cases, a recurrent tumor or

Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results

International Nuclear Information System (INIS)

Sugawara, Yoshifumi; Kison, P.V.; Russo, J.E.; Zasadny, K.R.; Braun, D.K.; Wahl, R.L.

1998-01-01

The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50-60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method. (orig.)

Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

International Nuclear Information System (INIS)

Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

2010-01-01

Introduction: Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis. Methods: [ 18 F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 deg. C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results: In vitro stability studies demonstrated that [ 18 F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but 18 F-labeled rhodamines should accumulate in the heart. Conclusions: [ 18 F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18 F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

Usefulness of Whole-Body Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Patients with Neurofibromatosis Type 1: A Systematic Review

Directory of Open Access Journals (Sweden)

Giorgio Treglia

2012-01-01

Full Text Available Aim. To systematically review the role of positron emission tomography (PET with fluorine-18-fluorodeoxyglucose (FDG in patients with neurofibromatosis type 1 (NF1. Methods. A comprehensive literature search of published studies regarding FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit and language restriction were used; the search was updated until December 2011. Only those studies or subsets in studies including whole-body FDG-PET or PET/CT scans performed in patients with NF1 were included. Results. We identified 12 studies including 352 NF1 patients. Qualitative evaluation was performed in about half of the studies and semiquantitative analysis, mainly based on different values of SUV cutoff, in the others. Most of the studies evaluated the role of FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors (MPNSTs. Malignant lesions were detected with a sensitivity ranging between 100% and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG-PET seems to be an important imaging modality for predicting the progression to MPNST and the outcome in patients with MPNST. Two studies evaluated the role of FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are useful methods to identify malignant change in neurogenic tumors in NF1 and to discriminate malignant from benign neurogenic lesions.

Usefulness of Whole-Body Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Patients with Neurofibromatosis Type 1: A Systematic Review

International Nuclear Information System (INIS)

Treglia, G.; Taralli, S.; Giordano, A.; Bertagna, F.; Salsano, M.; Maggi, F.; Muoio, B.; Novellis, P.; Vita, M.L.

2012-01-01

To systematically review the role of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). Methods. A comprehensive literature search of published studies regarding FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit and language restriction were used; the search was updated until December 2011. Only those studies or subsets in studies including whole-body FDG-PET or PET/CT scans performed in patients with NF1 were included. Results. We identified 12 studies including 352 NF1 patients. Qualitative evaluation was performed in about half of the studies and semiquantitative analysis, mainly based on different values of SUV cutoff, in the others. Most of the studies evaluated the role of FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors (MPNSTs). Malignant lesions were detected with a sensitivity ranging between 100% and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG-PET seems to be an important imaging modality for predicting the progression to MPNST and the outcome in patients with MPNST. Two studies evaluated the role of FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are useful methods to identify malignant change in neurogenic tumors in NF1 and to discriminate malignant from benign neurogenic lesions

Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone

International Nuclear Information System (INIS)

Talbot, J-N.; Montravers, F.; Huchet, V.; Michaud, L.; Ohnona, J.; Balogova, S.; Kerrou, K.; Gligorov, V.; Lotz, P.; Nataf, V.; Cussenot, O.; Darai, E.

2015-01-01

Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18 F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-( 18 F]fluoro-17β-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV m ax or FES/FDG SUV max ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical

Imaging of large vessel vasculitis with {sup 18}FDG PET: illusion or reality? A critical review of the literature data

Energy Technology Data Exchange (ETDEWEB)

Belhocine, Tarik; Vandevivere, Johan [Department of Nuclear Medicine, A.Z. Middelheim Hospital, 2020, Antwerp (Belgium); Blockmans, Daniel [Department of Internal Medicine, Gasthuisberg University Hospital, Leuven (Belgium); Hustinx, Roland [Department of Nuclear Medicine, University Hospital of Liege, Liege (Belgium); Mortelmans, Luc [Department of Nuclear Medicine, Gasthuisberg University Hospital, Leuven (Belgium)

2003-09-01

Fluorine-18 fluorodeoxyglucose positron emission tomography ({sup 18}FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of {sup 18}FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the {sup 18}FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging. (orig.)

The Label Matters: μPET Imaging of the Biodistribution of Low Molar Mass 89Zr and 18F-Labeled Poly(2-ethyl-2-oxazoline).

Science.gov (United States)

Glassner, Mathias; Palmieri, Luca; Monnery, Bryn D; Verbrugghen, Thomas; Deleye, Steven; Stroobants, Sigrid; Staelens, Steven; Wyffels, Leonie; Hoogenboom, Richard

2017-01-09

Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

International Nuclear Information System (INIS)

Herth, Matthias M.; Petersen, Ida Nymann; Hansen, Hanne Demant; Hansen, Martin; Ettrup, Anders; Jensen, Anders A.; Lehel, Szabolcs; Dyssegaard, Agnete; Gillings, Nic; Knudsen, Gitte M.

2016-01-01

Introduction: The serotonin 2A receptor (5-HT 2A R) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins and processes in the human brain and several 5-HT 2A R PET antagonist radioligands are available. In contrast to an antagonist radioligand, an agonist radioligand should be able to image the population of functional receptors, i.e., those capable of inducing neuroreceptor signaling. Recently, we successfully developed and validated the first 5-HT 2A R agonist PET tracer, [ 11 C]Cimbi-36, for neuroimaging in humans and herein disclose some of our efforts to develop an 18 F-labeled 5-HT 2A R agonist PET-ligand. Methods and results: Three fluorine containing derivatives of Cimbi-36 were synthesized and found to be potent 5-HT 2A agonists. 18 F-labeling of the appropriate precursors was performed using [ 18 F]FETos, typically yielding 0.2–2.0 GBq and specific activities of 40–120 GBq/μmol. PET studies in Danish landrace pigs revealed that [ 18 F]1 displayed brain uptake in 5-HT 2A R rich regions. However, high uptake in bone was also observed. No blocking effect was detected during a competition experiment with a 5-HT 2A R selective antagonist. [ 18 F]2 and [ 18 F]3 showed very low brain uptake. Conclusion: None of the investigated 18 F-labeled Cimbi-36 derivatives [ 18 F]1, [ 18 F]2 and [ 18 F]3 show suitable tracer characteristics for in vivo PET neuroimaging of the 5-HT 2A R. Although for [ 18 F]1 there was reasonable brain uptake, we suggest that a large proportion radioactivity in the brain was due to radiometabolites, which would explain why it could not be displaced by a 5-HT 2A R antagonist.

{sup 18}FDG PET and acetazolamide-enhanced {sup 99m}Tc-HMPAO SPET in systemic lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Gruenwald, F. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Schomburg, A. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Badali, A. [Dept. of Dermatology, Univ. of Bonn (Germany); Ruhlmann, J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Pavics, L. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Biersack, H.J. [Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin

1995-09-01

In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) and a PET scan with fluorine-18 deoxyglucose ({sup 18}FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that ``preclinical`` CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE. (orig.). With 2 figs.

Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy

DEFF Research Database (Denmark)

Kjaer, Andreas; Lebech, Anne-Mette; Eigtved, Annika

2004-01-01

The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron...... emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and (111)In......-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious...

Early diagnosis and follow-up of aortitis with [{sup 18}F]FDG PET and MRI

Energy Technology Data Exchange (ETDEWEB)

Meller, J.; Siefker, U.; Sahlmann, C.O.; Lehmann, K.; Conrad, M. [Department of Nuclear Medicine, Georg August University, Robert Koch-Strasse 40, 37075, Goettingen (Germany); Strutz, F.; Scheel, A. [Department of Nephrology and Rheumatology, Georg August University, Goettingen (Germany); Vosshenrich, R. [Department of Radiology, Georg August University, Goettingen (Germany)

2003-05-01

The aim of this prospective study was to compare fluorine-18 fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) with magnetic resonance imaging (MRI) in patients with early aortitis, at the time of initial diagnosis and during immunosuppressive therapy. The study population consisted of 15 patients (nine females and six males; median age 62 years, range 26-76 years) who presented with fever of unknown origin or an elevated erythrocyte sedimentation rate or elevated C-reactive protein and who showed pathological aortic [{sup 18}F]FDG uptake. Fourteen of these patients had features of early giant cell arteritis (GCA), while one had features of early Takayasu arteritis. During follow-up, seven PET scans were performed in six patients with GCA 4-30 months (median 19 months) after starting immunosuppressive medication. The results of [{sup 18}F]FDG imaging were compared with the results of MRI at initial evaluation and during follow-up and with the clinical findings. At baseline, abnormal [{sup 18}F]FDG uptake was present in 59/104 (56%) of the vascular regions studied in 15 patients. Seven follow-up PET studies were performed in six patients. Of 30 regions with initial pathological uptake in these patients, 24 (80%) showed normalisation of uptake during follow-up. Normalisation of [{sup 18}F]FDG uptake correlated with clinical improvement and with normalisation of the laboratory findings. All except one of the patients with positive aortic [{sup 18}F]FDG uptake were investigated with MRI and MRA. Thirteen of these 14 patients showed inflammation in at least one vascular region. Of 76 vascular regions studied, 41 (53%) showed vasculitis on MRI. Of 76 vascular regions studied with both PET and MRI, 47 were concordantly positive or negative on both modalities, 11 were positive on MRI only and 18 were positive on PET only. MRI was performed during follow-up in six patients: of 17 regions with inflammatory changes, 15 regions remained unchanged and two

Radiolabeled Peptide Scaffolds for PET/SPECT - Optical in Vivo Imaging of Carbohydrate-Lectin Interactions

Energy Technology Data Exchange (ETDEWEB)

Deutscher, Susan

2014-09-30

The objective of this research is to develop phage display-selected peptides into radio- and fluoresecently- labeled scaffolds for the multimodal imaging of carbohydrate-lectin interactions. While numerous protein and receptor systems are being explored for the development of targeted imaging agents, the targeting and analysis of carbohydrate-lectin complexes in vivo remains relatively unexplored. Antibodies, nanoparticles, and peptides are being developed that target carbohydrate-lectin complexes in living systems. However, antibodies and nanoparticles often suffer from slow clearance and toxicity problems. Peptides are attractive alternative vehicles for the specific delivery of radionuclides or fluorophores to sites of interest in vivo, although, because of their size, uptake and retention may be less than antibodies. We have selected high affinity peptides that bind a specific carbohydrate-lectin complex involved in cell-cell adhesion and cross-linking using bacteriophage (phage) display technologies (1,2). These peptides have allowed us to probe the role of these antigens in cell adhesion. Fluorescent versions of the peptides have been developed for optical imaging and radiolabeled versions have been used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) in vivo imaging (3-6). A benefit in employing the radiolabeled peptides in SPECT and PET is that these imaging modalities are widely used in living systems and offer deep tissue sensitivity. Radiolabeled peptides, however, often exhibit poor stability and high kidney uptake in vivo. Conversely, optical imaging is sensitive and offers good spatial resolution, but is not useful for deep tissue penetration and is semi-quantitative. Thus, multimodality imaging that relies on the strengths of both radio- and optical- imaging is a current focus for development of new in vivo imaging agents. We propose a novel means to improve the efficacy of radiolabeled and fluorescently

(18)F-nanobody for PET imaging of HER2 overexpressing tumors.

Science.gov (United States)

Xavier, Catarina; Blykers, Anneleen; Vaneycken, Ilse; D'Huyvetter, Matthias; Heemskerk, Jan; Lahoutte, Tony; Devoogdt, Nick; Caveliers, Vicky

2016-04-01

Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with (18)F and its validation for in vivo assessment of HER2 overexpression. The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models. [(18)F]FB-anti-HER2 nanobody was prepared with a 5-15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3h p.i.). [(18)F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. The GMP grade anti-HER2 nanobody was labeled with (18)F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation. Copyright © 2016 Elsevier Inc. All rights reserved.

18F-nanobody for PET imaging of HER2 overexpressing tumors

International Nuclear Information System (INIS)

Xavier, Catarina; Blykers, Anneleen; Vaneycken, Ilse; D'Huyvetter, Matthias; Heemskerk, Jan; Lahoutte, Tony; Devoogdt, Nick; Caveliers, Vicky

2016-01-01

Introduction: Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with 18 F and its validation for in vivo assessment of HER2 overexpression. Methods: The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models. Results: [ 18 F]FB-anti-HER2 nanobody was prepared with a 5–15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3 h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3 h p.i.). [ 18 F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. Conclusions: The GMP grade anti-HER2 nanobody was labeled with 18 F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation.

Physiologic uptake of 18F-FDG in transposed ovaries may mimic metastasis on 18F-FDG PET/CT imaging.

Science.gov (United States)

Davidson, Tima; Komisar, Orna; Korach, Jacob; Felder, Shira; Apter, Sara; Ben-Haim, Simona; Perri, Tamar

2018-02-01

Ovarian transposition is aimed at preserving ovarian function before irradiation in pelvic malignancies. The extrapelvic location of the ovaries and their physiologic fluorine-18-fluorodeoxyglucose (F-FDG)-uptake is a potential source of misdiagnosis as metastasis on F-FDG PET/CT. We describe the F-FDG PET/CT characteristics of transposed ovaries and their changes over time. We reviewed F-FDG PET/CT studies of all consecutive women with pelvic malignancies who underwent ovarian transposition between 2007 and 2013. Studies were grouped according to the time period over which they were carried out. Findings were categorized by location, size, appearance (solid/mixed/cystic), presence of surgical clips, ovarian F-FDG uptake (maximum standardized uptake value), and attenuation values on CT (Hounsfield units). Group time-period differences were assessed. Seventy-nine F-FDG PET/CT studies were reviewed, 30 before and 49 after transposition. Time-period groups after transposition were up to 4 months (18 studies), 4.1-12 months (n=14), and more than 12 months (n=17). After transposition, ovaries were located mainly in the paracolic gutter (n=32) and subhepatic regions (n=18). Surgical clips were present in 67%. Both ovaries appeared more solid 1 year after surgery than preoperatively (13.7% before vs. 61.3% after surgery; P<0.001). Transient F-FDG-avidity was observed in 11 ovaries. Hounsfield unit values were higher within 4 months after surgery than preoperatively, reverting thereafter to preoperative values. After ovarian transposition, nonanatomic location, loss of cysts formation in favor of solid appearance over time, and intermittent F-FDG uptake of functioning transposed ovaries might mimic metastatic lesions. Careful interpretation of F-FDG PET/CT findings is mandatory in women with pelvic malignancies who have undergone ovarian transposition.

The role of PET/CT in evaluation of Facet and Disc abnormalities in patients with low back pain using 18Fluorine

International Nuclear Information System (INIS)

Gamie, S.; El-Maghraby, T.

2008-01-01

Bone scintigraphy including Single Photon Emission Computed Tomography (SPECT) is known for its role in the diagnosis of low back pain disorders. Positron Emission Tomography (PET) with 18 Fluoride) as a tracer can be used to carry out bone scans with improved image quality. With the addition of CT, simultaneous PET/CT fused images provide more accurate anatomical details. The objectives of this work are E VCT 64-Slice combined scanner. Imaging started 45-60 minutes after administration of 12-15 mCi (444-55 MBq) of 18 F-Fluoride. The PET scan was acquired from the skull base through the inguinal region in 3D mode at 2 minutes/bed. A low resolution, non-contrast CT scan was also acquired for anatomic localization and attenuation correction. The 18 F-PET/CT showed abnormal uptake in the spine in 56 patients, with an overall detection ability of 84%. Facet joints as a cause of back pain was much more frequent (25 with abnormal scans). One-third (36%) of the patients showed multiple positive uptake in both facet joints and disc areas (20/56). The patients were further divided into two groups. Group A consisted of 42 patients (63%) with back pain and no previous operative procedures, and the 18 F-PET/CT showed a high sensitivity (88%) in identifying the source of pain in 37/42 patients. Group B included 25 patients (37%) with prior lumbar fusion or laminectomy, in which the PET/CT showed positive uptake in 76% (19/25 patients). 18 F-PET/CT showed positive uptake in all patients (100%) with a history of pain after lumbar fusion, while in the laminectomy subgroup only 11 cases (65%) showed positive focal uptake. 18 FPET-CT has potential use in evaluating adult patients with back pain. It has a promising role in identifying causes of persistent back pain following vertebral surgical interventions. (authors)

Development of (F-18)-Labeled Amyloid Imaging Agents for PET

International Nuclear Information System (INIS)

Mathis, C.A.

2007-01-01

The applicant proposes to design and synthesize a series of fluorine-18-labeled radiopharmaceuticals to be used as amyloid imaging agents for positron emission tomography (PET). The investigators will conduct comprehensive iterative in vitro and in vivo studies based upon well defined acceptance criteria in order to identify lead agents suitable for human studies. The long term goals are to apply the selected radiotracers as potential diagnostic agents of Alzheimer's disease (AD), as surrogate markers of amyloid in the brain to determine the efficacy of anti-amyloid therapeutic drugs, and as tools to help address basic scientific questions regarding the progression of the neuropathology of AD, such as testing the 'amyloid cascade hypothesis' which holds that amyloid accumulation is the primary cause of AD.

Study of the chemical species of fluorine 18 produced by neutron irradiation of lithium aluminate

International Nuclear Information System (INIS)

Jimenez-Becerril, J.

1990-01-01

In the present work, the chemical form of fluorine-18 obtained by means of the neutron irradiated lithium aluminate was studied, in order to know its chemical behavior and to observe if it volatilizes and adheres to the walls of a tritium distillation system; for this matter paper chromatography and high voltage electrophoresis techniques were used. Lithium aluminate was synthetized, being characterized as LiAlO 2 which was irradiated with neutrons in order to produce fluorine-18. Lithium aluminate is a non-soluble solid, therefore fluorine produced may not be extracted, unless it is dissolved or extracted through the solid. So as not affect in a drastic way the chemical form, it was submitted to extraction processes, agitating the irradiated samples with different acids and basic solutions in order to analyze fluorine-18. The best extraction agent was found to be HCl, where two forms of fluorine-18 were found, one at the point of application, probably as a complex hexafluoride-aluminate and the other as a characteristic Rf of the fluorine ion. In the tritium distillation with helium as a carrier of a sample irradiated and heated up to 220-250 o C, no volatile types of fluorine-18 were found, thus it can be considered that in commercial production of tritium by means of neutron irradiation of lithium aluminate, fluorine-18 is not a damaging pollutant of the equipment pipe system. (Author)

Ability of 18F-DOPA PET/CT and fused 18F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

International Nuclear Information System (INIS)

Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Puntoni, Matteo; Garre, Maria Luisa; Massollo, Michela; Naseri, Merhdad; Piccardo, Arnoldo; Lopci, Egesta

2016-01-01

To assess the diagnostic performance of 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with 18 F-DOPA PET/CT and brain MRI. Fused 18 F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for 18 F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for 18 F-DOPA PET/CT, respectively. 18 F-DOPA PET/MRI showed a trend towards higher accuracy compared with 18 F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with 18 F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and 18 F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of 18 F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the 18 F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by 18 F-DOPA PET/MRI. Physiological striatal 18 F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement. 18 F-DOPA PET/CT correctly detected

Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine

International Nuclear Information System (INIS)

Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt; Asenbaum, Susanne; Marosi, Christine; Henk, Christine; Wunderbaldinger, Patrick; Czech, Thomas

2003-01-01

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[ 18 F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean±SD), were 2.05±0.91 for MET and 2.04±0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of 18 F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

[18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey

International Nuclear Information System (INIS)

Hostetler, Eric D.; Sanabria-Bohórquez, Sandra; Fan Hong; Zeng, Zhizhen; Gammage, Linda; Miller, Patricia; O'Malley, Stacey; Connolly, Brett; Mulhearn, James; Harrison, Scott T.; Wolkenberg, Scott E.; Barrow, James C.; Williams, David L.; Hargreaves, Richard J.; Sur, Cyrille; Cook, Jacquelynn J.

2011-01-01

Introduction: An 18 F-labeled positron emission tomography (PET) tracer for amyloid plaque is desirable for early diagnosis of Alzheimer's disease, particularly to enable preventative treatment once effective therapeutics are available. Similarly, such a tracer would be useful as a biomarker for enrollment of patients in clinical trials for evaluation of antiamyloid therapeutics. Furthermore, changes in the level of plaque burden as quantified by an amyloid plaque PET tracer may provide valuable insights into the effectiveness of amyloid-targeted therapeutics. This work describes our approach to evaluate and select a candidate PET tracer for in vivo quantification of human amyloid plaque. Methods: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood–brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with 18 F and evaluated in vivo. Baseline PET scans in rhesus monkey were conducted to evaluate the regional distribution and kinetics of each tracer using tracer kinetic modeling methods. High binding potential in cerebral white matter and cortical grey matter was considered an unfavorable feature of the candidate tracers. Results: [ 18 F]MK-3328 showed the most favorable combination of low in vivo binding potential in white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log D=2.91) and high affinity for human amyloid plaques (IC 50 =10.5±1.3 nM). Conclusions: [ 18 F]MK-3328 was identified as a promising PET tracer for in vivo quantification of amyloid plaques, and further evaluation in humans is warranted.

Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18f]fluorobenzoate

International Nuclear Information System (INIS)

Jonson, Stephanie D.; Welch, Michael J.

1999-01-01

Cholesteryl-p-[ 18 F]fluorobenzoate ([ 18 F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [ 18 F]CFB. The synthesis of [ 18 F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [ 18 F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [ 18 F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [ 18 F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [ 18 F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [ 18 F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [ 18 F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders

Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases

Directory of Open Access Journals (Sweden)

Tetsuro Tago

2018-01-01

Full Text Available Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs, which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET. We summarize the results of radiosynthesis and biological evaluation of the HDAC ligands to identify their successful results and challenges. Since 2006, several small molecules that are radiolabeled with a radioisotope such as carbon-11 or fluorine-18 have been developed and evaluated using various assays including in vitro HDAC binding assays and PET imaging in rodents and non-human primates. Although most compounds do not readily cross the blood-brain barrier, adamantane-conjugated radioligands tend to show good brain uptake. Until now, only one HDAC radioligand has been tested clinically in a brain PET study. Further PET imaging studies to clarify age-related and disease-related changes in HDACs in disease models and humans will increase our understanding of the roles of HDACs in neurodegenerative diseases.

Remote-controlled module-assisted synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine as tumor PET tracer using two different radiochemical routes

International Nuclear Information System (INIS)

Wang Mingwei; Yin Duanzhi; Zhang Lan; Zhou Wei; Wang Yongxian

2006-01-01

The positron-emitter fluorine-18 labeled amino acid O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) has shown very promising perspectives for brain tumor diagnosis with positron emission tomography (PET). There have been two existing preparation routes of [ 18 F]FET named direct nucleophilic radiofiuorination of protected L-tyrosine and radiofiuoroallcylation of unprotected L-tyrosine, respectively. A general module was designed specifically for the routine synthesis of [ 18 F]FET, which could be suitable for the present two chemical methods with simple modifications. The fluorinated intermediates and the final product were separated and purified using solid phase extraction (SPE) on the Sep-Pak silica plus cartridge instead of the time-consuming high performance liquid chromatography (HPLC) procedures. The total synthesis time was about 50-60 rain with good radiochemical yield (about 20-40%, no-decay-corrected) and good radiochemical purity (more than 97%) for both the synthetic methods. (authors)

The optimization of 18F-nucleophilic fluorination reaction and its application in synthesis of VMAT2 imaging tracer: [18F]AV-133

International Nuclear Information System (INIS)

Liu Yajing; Zhu Lin; Karl, P.; Qu Wenchao

2010-01-01

Objective: The nucleophilic introduction of n.c.a. [ 18 F]F- into alkanes by nucleophilic reaction is the main method of preparing 18 F-labelled radiopharmaceuticals, and the efficient and rapid reaction is important in 18 F-labelled radiopharmaceuticals. Method: Using 2-(3-substitute propoxy)naphthalene as model compound, the optimal reaction condition was achieved by comparing the different [ 18 F]fluorination condition: 1)different leaving groups (-OTs, -I, -Br and -Cl), 2) different [ 18 F]fluorination catalysts (Kryptofix222/K 2 CO 3 and TBAHCO 3 ), 3) different reaction solvent (ACN, DMSO and DMF), 4) [ 18 F]fluorination temperature (40, 50 and 60 degree C) and 5) reaction time. The radiochemical yields were analyzed by TLC and HPLC. VMAT2 imaging tracer [ 18 F]AV-133 was synthesized under the optimal conditions. Results: From the experiment results, the reation activity was the highest when using -OTs as the leaving group, followed by -I and -Br, -Clunder the [ 18 F]fluorination condition of using K222/K 2 CO 3 as catalyst and ACN as solvent. And also, the radiochemical yield raised as the reaction time and temperature increased. The higher temperature, the shorter time to reach the equilibrium. When changing the solvent from ACN to DMSO, the radiochemical yields were increased. On the contrary, the radiochemical yields were decreasing by using DMF. Comparing the catalyst K222/K 2 CO 3 with TBAHCO 3 , the [ 18 F] fluorination of -OTs gave a higher radiochemical yield in the presence of K222/K 2 CO 3 . So the optimized [ 18 F]fluorination reaction condition was that choosing -OTs as the leaving group, the [ 18 F]fluorination reaction was efficient and gave higher radiochemical yield catalyzed by K222/K 2 CO 3 in DMSO at high temperature. [ 18 F]fluorination of AV-244 was found to provide the VMAT2 imaging tracer [ 18 F]AV-133 in 80 ± 2% radiochemical yield after reaction at 120 degree C for 3 min under optimized conditions. Conclusion: We have described an

The fluorodediazonation - a method for n.c.a.-18F-labelling of aromatic substrates

International Nuclear Information System (INIS)

Zwernemann, O.

1991-06-01

For the positron emission tomography (PET) applications, radiopharmaceuticals are required that are labelled with short-lived positron emitters. Fluorine-18 has become the leading radionuclide used for PET, due to its favourable physical properties. However, the labelling of aromatic substances with fluorine-18 with the methods available presents problems not encountered with aliphatic compounds. The decomposition of aromatic diazonium salts opens up feasible ways of preparing a broad range of labelled compounds. The dissertation investigated the possibilities of labelling with fluorine-18 by way of dediazonation on the standard substrate p-Toluidyl diazonium ion. The results reported show that the method of fluorodediazonation is an interesting further method for F-18 labelling of aromatic substrates in addition to the hitherto applied techniques. It allows carrier-free labelling of a large group of substances which cannot be fluorinated via direct nucleophilicity. (BBR) [de

[Usefulness of (18)FDG PET-CT scan as a diagnostic tool of fever of unknown origin].

Science.gov (United States)

García-Gómez, Francisco Javier; Acevedo-Báñez, Irene; Martínez-Castillo, Rubén; García-Gutiérrez, Manuel; Tirado-Hospital, Juan Luis; Borrego-Dorado, Isabel

2015-07-20

Classic fever of unknown origin (FUO) is defined as the presence of fever greater than 38.3°C of at least 3 weeks with an uncertain diagnosis. Identification of the etiology is crucial in guiding further diagnostic procedures and subsequent patient management. The aim of this study was to evaluate the role of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography combined with computed tomography (PET/CT) in the diagnostic orientation of FUO. An observational retrospective study was performed, including 30 consecutive patients who had been studied between March 2010 and September 2013. Twenty-six out of 30 patients (86.67%) had a definitive diagnosis after pathologic confirmation in 15 cases, microbiological findings in one patient and clinical and radiological follow-up in 10 patients (mean: 16.38 months). Among the positive scans, malignancy (n=10), inflammatory (n=8), infectious (n=4) and miscellaneous causes (n=1) were identified. (18)F-FDG PET/CT had a diagnostic accuracy of 90.00%, sensitivity of 88.46% (95% confidence interval [95% CI] 76-101), specificity of 100.00% (95% CI 100-100), positive predictive values of 100.00% (95% CI100-100) and negative predictive value of 57.14% (95% CI 20-91). (18)F-FDG PET/CT provided useful for the etiologic diagnosis of FUO, with high sensitivity and specificity. (18)F-FDG PET/CT has an incremental morphological and functional value, especially indicating the best biopsy site. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

PET and SPET tracers for mapping the cardiac nervous system

International Nuclear Information System (INIS)

Langer, Oliver; Halldin, Christer

2002-01-01

The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[ 18 F]fluorodopamine, (-)-6-[ 18 F]fluoronorepinephrine and (-)-[ 11 C]epinephrine, and radiolabelled catecholamine analogues, such as [ 123 I]meta-iodobenzylguanidine, [ 11 C]meta-hydroxyephedrine, [ 18 F]fluorometaraminol, [ 11 C]phenylephrine and meta-[ 76 Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[ 18 F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility for cardiac neuronal imaging. (orig.)

Solitary Plasmacytoma of the Sternum Mimicking Bone Metastasis in a Patient with a History of Breast Cancer Evaluated by F-18-FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio; Luca, Giovanella [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Barbara, Muoio; Carmelo, Caldarella [Catholic Univ., Rome (Italy)

2014-06-15

A 65-year-old woman with a history of breast cancer (stage T2N0M0 treated with left breast conservative therapy 7 years previously followed by hormone therapy) underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) for restaging due to increased serum tumour markers levels (CA15-3, 37 U/ml and CEA, 8 ng/ml). The patient presented thoracic pain before performing F-18-FDG PET/CT. PET/CT demonstrated an area of increased F-18-FDG uptake corresponding to an osteolytic lesion occupying the upper sternum suspicious for bone metastasis. No other areas of abnormal F-18-FDG uptake were detected in the rest of the body. Based on this PET/CT finding, the patient performed biopsy of the sternal lesion. Histology demonstrated the presence of a sternal plasmacytoma and the patient was addressed to radiation therapy. The role of F-18-FDG PET/CT in patients with multiple myeloma is well known, whereas only some articles evaluated the usefulness of this method in patients with solitary plasmacytomas. In particular, F-18-FDG PET/CT may be useful in demonstrating the evolution of solitary plasmacytomas in multiple myeloma. In our case F-18-FDG PET/CT was useful in detecting a solitary plasmacytoma of the sternum mimicking bone metastasis in a patient with history of breast cancer, correctly addressing to further histological evaluation.

Solitary Plasmacytoma of the Sternum Mimicking Bone Metastasis in a Patient with a History of Breast Cancer Evaluated by F-18-FDG PET/CT

International Nuclear Information System (INIS)

Treglia, Giorgio; Luca, Giovanella; Barbara, Muoio; Carmelo, Caldarella

2014-01-01

A 65-year-old woman with a history of breast cancer (stage T2N0M0 treated with left breast conservative therapy 7 years previously followed by hormone therapy) underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) for restaging due to increased serum tumour markers levels (CA15-3, 37 U/ml and CEA, 8 ng/ml). The patient presented thoracic pain before performing F-18-FDG PET/CT. PET/CT demonstrated an area of increased F-18-FDG uptake corresponding to an osteolytic lesion occupying the upper sternum suspicious for bone metastasis. No other areas of abnormal F-18-FDG uptake were detected in the rest of the body. Based on this PET/CT finding, the patient performed biopsy of the sternal lesion. Histology demonstrated the presence of a sternal plasmacytoma and the patient was addressed to radiation therapy. The role of F-18-FDG PET/CT in patients with multiple myeloma is well known, whereas only some articles evaluated the usefulness of this method in patients with solitary plasmacytomas. In particular, F-18-FDG PET/CT may be useful in demonstrating the evolution of solitary plasmacytomas in multiple myeloma. In our case F-18-FDG PET/CT was useful in detecting a solitary plasmacytoma of the sternum mimicking bone metastasis in a patient with history of breast cancer, correctly addressing to further histological evaluation

Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia

International Nuclear Information System (INIS)

Laurens, Evelyn; Yeoh, Shinn Dee; Rigopoulos, Angela; Cao, Diana; Cartwright, Glenn A.; O'Keefe, Graeme J.; Tochon-Danguy, Henri J.; White, Jonathan M.; Scott, Andrew M.; Ackermann, Uwe

2014-01-01

[ 18 F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [ 18 F]FMISO a 2 h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides. In this manuscript we report on the synthesis, in vitro and in vivo evaluation of a novel fluoroethyltriazolyl propargyl anilino sulfoxide. The radiolabelling of the novel tracer was achieved via 2-[ 18 F]fluoroethyl azide click chemistry. Radiochemical yields were 23 ± 4% based on 2-[ 18 F]fluoroethyl azide and 7 ± 2% based on K[ 18 F]F. The radiotracer did not undergo metabolism or defluorination in an in vitro assay using S9 liver fractions. Imaging studies using SK-RC-52 tumors in BALB/c nude mice have indicated that the tracer may have a higher pO 2 threshold than [ 18 F]FMISO for uptake in hypoxic tumors. Although clearance from muscle was faster than [ 18 F]FMISO, uptake in hypoxic tumors was slower. The average tumor to muscle ratio at 2 h post injection in large, hypoxic tumors with a volume greater than 686 mm 3 was 1.7, which was similar to the observed ratio of 1.75 for [ 18 F]FMISO. Although the new tracer showed improved pharmacokinetics when compared with the previously synthesised sulfoxides, further modifications to the chemical structure need to be made in order to offer significant in vivo imaging advantages over [ 18 F]FMISO

Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936

International Nuclear Information System (INIS)

Risgaard, Rune; Ettrup, Anders; Balle, Thomas; Dyssegaard, Agnete; Hansen, Hanne Demant; Lehel, Szabolcs; Madsen, Jacob; Pedersen, Henrik; Püschl, Ask; Badolo, Lassina; Bang-Andersen, Benny; Knudsen, Gitte Moos; Kristensen, Jesper Langgaard

2013-01-01

Cerebral α 1 -adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α 1 -adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs targeting the α 1 -adrenoceptors. However, so far no suitable PET radioligand has been developed for brain imaging of α 1 -adrenoceptors. Here, we report the synthesis of both enantiomers of the desmethyl precursors of the high affinity α 1 -adrenoceptor ligand Lu AE43936 (). The two enantiomers of were subsequently [ 11 C] radiolabelled and evaluated for brain uptake and binding by PET imaging in Danish Landrace pigs. (S)-[ 11 C]- and (R)-[ 11 C]- showed very limited brain uptake. Pre-treatment with cyclosporine A (CsA) resulted in a large increase in brain uptake, indicating that (R)-[ 11 C]- is a substrate for active efflux-transporters. This was confirmed in Madin Darby canine kidney (MDCK) cells overexpressing permeability glycoprotein (Pgp). In conclusion, the limited brain uptake of both (S)-[ 11 C]- and (R)-[ 11 C]- in the pig brain necessitates the search for alternative radioligands for in vivo PET brain imaging of α 1 -adrenoceptors.

Do the metabolites of 6-[F-18]fluoro-L-dopa and of [F-18]fluoro-meta-L-tyrosine contribute to the F-18 accumulation in the human brain?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

The purpose of this study was to determine if the metabolites of 6-[F-18]fluoro-L-dopa (F-dopa) and of [F-18]fluoro-meta-L-tyrosine (FmLtyr) contribute to the accumulation of fluorine-18 in the brain through unspecific retention. PET studies were conducted on a healthy human subject who was treated with both of the radiopharmaceuticals and their labelled metabolites. Results indicated that in contrast to F-dopa, the metabolite of FmLtyr does not 'contaminate' the brain with extraneous fluorine-18

Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

2008-01-01

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[{sup 18}f]fluorobenzoate

Energy Technology Data Exchange (ETDEWEB)

Jonson, Stephanie D.; Welch, Michael J. E-mail: welch@mirlink.wustl.edu

1999-01-01

Cholesteryl-p-[{sup 18}F]fluorobenzoate ([{sup 18}F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [{sup 18}F]CFB. The synthesis of [{sup 18}F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [{sup 18}F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [{sup 18}F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [{sup 18}F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [{sup 18}F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [{sup 18}F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [{sup 18}F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders.

Methoxyphenylethynyl, methoxypyridylethynyl and phenylethynyl derivatives of pyridine: synthesis, radiolabeling and evaluation of new PET ligands for metabotropic glutamate subtype 5 receptors

International Nuclear Information System (INIS)

Yu Meixiang; Tueckmantel, Werner; Wang, Xukui; Zhu Aijun; Kozikowski, Alan P.; Brownell, Anna-Liisa

2005-01-01

We have synthesized three different PET ligands to investigate the physiological function of metabotropic glutamate subtype 5 receptors (mGluR5) in vivo: 2-[ 11 C]methyl-6-(2-phenylethynyl)pyridine ([ 11 C]MPEP), 2-(2-(3-[ 11 C]methoxyphenyl)ethynyl)pyridine ([ 11 C]M-MPEP) and 2-(2-(5-[ 11 C]methoxypyridin-3-yl)ethynyl)pyridine ([ 11 C]M-PEPy). [ 11 C]Methyl iodide was used to label the compounds under basic conditions, and a Pd(0) catalyst was applied to label [ 11 C]MPEP in a Stille coupling reaction. In vivo microPET imaging studies of the functional accumulation of radiolabeled ligands were conducted in 35 rats (Sprague-Dawley, 8 weeks old male, weight of 300 g). Specific binding was tested using pre-administration of unlabeled mGluR5 antagonist 2-methyl-6-(2-phenylethynyl)pyridine (MPEP) (10 mg/kg iv 5 min before radioactivity injection). In the radiolabeling of [ 11 C]MPEP, [ 11 C]M-MPEP and [ 11 C]M-PEPy, a specific radioactivity of 700-1200 mCi/μmol and over 97% radiochemical purity were obtained. The microPET studies showed these three radiolabeled mGluR5 antagonists having the highest binding in the olfactory bulb followed by striatum, hippocampus and cortex. Pre-administration of the mGluR5 antagonist MPEP induced a 45.1% decrease in [ 11 C]MPEP binding, a 59.7% decrease in [ 11 C]M-MPEP binding and an 84.6% decrease in [ 11 C]M-PEPy binding in the olfactory bulb at 5 min. The feasibility of synthesizing high-affinity and high-selectivity ligands for mGluR5 receptors and their suitability as PET imaging ligands for mGluR5 receptors in vivo are demonstrated

Brain penetrant small molecule 18F-GnRH receptor (GnRH-R) antagonists: Synthesis and preliminary positron emission tomography imaging in rats

International Nuclear Information System (INIS)

Olberg, Dag E.; Bauer, Nadine; Andressen, Kjetil W.; Hjørnevik, Trine; Cumming, Paul; Levy, Finn O.; Klaveness, Jo; Haraldsen, Ira; Sutcliffe, Julie L.

2016-01-01

Introduction: The gonadotropin releasing hormone receptor (GnRH-R) has a well-described neuroendocrine function in the anterior pituitary. However, little is known about its function in the central nervous system (CNS), where it is most abundantly expressed in hippocampus and amygdala. Since peptide ligands based upon the endogenous decapetide GnRH do not pass the blood–brain-barrier, we are seeking a high-affinity small molecule GnRH-R ligand suitable for brain imaging by positron emission tomography. We have previously reported the radiosynthesis and in vitro evaluation of two novel [ 18 F]fluorinated GnRH-R ligands belonging to the furamide class of antagonists, with molecular weight less than 500 Da. We now extend this work using palladium coupling for the synthesis of four novel radioligands, with putatively reduced polar surface area and hydrophilicity relative to the two previously described compounds, and report the uptake of these 18 F-labeled compounds in brain of living rats. Methods: We synthesized reference standards of the small molecule GnRH-R antagonists as well as mesylate precursors for 18 F-labeling. The antagonists were tested for binding affinity for both human and rat GnRH-R. Serum and blood stability in vitro and in vivo were studied. Biodistribution and PET imaging studies were performed in male rats in order to assess brain penetration in vivo. Results: A palladium coupling methodology served for the synthesis of four novel fluorinated furamide GnRH receptor antagonists with reduced heteroatomic count. Radioligand binding assays in vitro revealed subnanomolar affinity of the new fluorinated compounds for both human and rat GnRH-R. The 18 F-GnRH antagonists were synthesized from the corresponding mesylate precursors in 5–15% overall radiochemical yield. The radiolabeled compounds demonstrated good in vivo stability. PET imaging with the 18 F-radiotracers in naive rats showed good permeability into brain and rapid washout, but absence of

Positron emission tomographic imaging of tumors using monoclonal antibodies

Energy Technology Data Exchange (ETDEWEB)

Zalutsky, M.R.

1992-08-01

This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.

Positron emission tomographic imaging of tumors using monoclonal antibodies. Progress report, April 15, 1992--October 31, 1992

Energy Technology Data Exchange (ETDEWEB)

Zalutsky, M.R.

1992-08-01

This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.

Combined early dynamic (18)F-FDG PET/CT and conventional whole-body (18)F-FDG PET/CT provide one-stop imaging for detecting hepatocellular carcinoma.

Science.gov (United States)

Wang, Shao-Bo; Wu, Hu-Bing; Wang, Quan-Shi; Zhou, Wen-Lan; Tian, Ying; Li, Hong-Sheng; Ji, Yun-Hai; Lv, Liang

2015-06-01

It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (PPET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P0.05, respectively). One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Synthesis of no-carrier-added fluorine-18 2-fluoro-2-deoxy-d-glucose

International Nuclear Information System (INIS)

Tewson, T.J.

1983-01-01

A new synthetic procedure for the preparation of fluorine-18 2-fluoro-2-deoxy-glucose has been developed. This procedure offers the advantages of flexibility in the source of the fluorine-18, high yields, and short synthesis times. The procedure works at the no-carrier-added level and gives a product of very high specific activity

Radiolabeled phosphonium salts as mitocondrial voltage sensors for positron emission tomography myocardial imaging agents

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Yon; Min, Jung Joon [Dept. of Nuclear Medicine,Chonnam National University Medical School and Hwasun Hospital, Gwangju (Korea, Republic of)

2016-09-15

Despite substantial advances in the diagnosis of cardiovascular disease, {sup 18}F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenyl phosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed.

Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

Science.gov (United States)

Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

2015-01-01

Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

Development of a kit-like radiofluorinated biomolecule leading to a controlled self-assembly of 18F nanoparticles for a smart PET imaging application.

Science.gov (United States)

Lin, Jianguo; Wang, Wei; Li, Ke; Huang, Hongbo; Lv, Gaochao; Peng, Ying; Luo, Shineng; Qiu, Ling

2017-06-13

A kit-like 18 F-fluorination method has been successfully applied to prepare an activatable probe 1 with good radiochemical yield and high specific activity. The probe has good in vitro stability and favorable cell membrane permeability. A controlled condensation reaction was initiated, and self-assembly into nanoparticles occurred when the probe was in a reducing environment. Positron emission tomography (PET) imaging of the biothiol level in living subjects was conveniently and precisely realized using this probe. The present study may provide a new platform for the development of "smart" PET tracers for tumor imaging.

[{sup 18}F]D.P.A.-714: a novel fluorine-18-labelled pyrazolo[1,5-a]pyrimidine acetamide for imaging the peripheral benzodiazepine receptors with PET - radiosynthesis on a zymate-xp robotic system

Energy Technology Data Exchange (ETDEWEB)

Dolle, F.; Damont, A.; Hinnen, F.; Kuhnast, B.; Chauveau, F.; Van camp, N.; Hantraye, P.; Tavitian, B. [Servvice Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); James, M.; Creelman, A.; Fulton, R.; Kassiou, M. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Vercouillie, J.; Guilloteau, D. [Universite Francois Rabelais de Tours, 37 (France); Vercouillie, J.; Guilloteau, D. [Centre Hospitalier Regional Universitaire, 37 - Tours (France); Selleri, S.; Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia)

2008-02-15

{sup 11}C D.P.A.-713 (N,N-diethyl-2-[2-(4-[{sup 11}C]methoxy-phenyl)-5,7-dimethyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) is a recently developed carbon-11-labelled (half life: 20.4 min)pyrazolo[1,5-a]pyrimidine acetamide for the in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.)). Preliminary results obtained in a rodent-model demonstrates that {sup 11}C D.P.A.-713 showed a high potential to in vivo image neuro-inflammation and additionally, this radioligand allowed a higher contrast between the lesioned area and the corresponding area in the intact contralateral hemisphere when compared to the radioligand of reference. D.P.A-714 (N,N-diethyl-2-[2-[4-(2-fluoro-ethoxy)phenyl] -5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]acetamide), a chemically closely related derivative of D.P.A.-713, had been designed with a fluorine atom in its structure, allowing ultimate labelling with fluorine-18, a longer-lived positron-emitter (half life:109.8 min) and today one of the most attractive PET isotopes for radiopharmaceutical chemistry. D.P.A.-714 as well as its corresponding tosylated derivative have been re-synthesized in 2 chemicals steps from D.P.A.-713. D.P.A.-714 has then been labelled at its aromatic fluoro-ethoxy group from the corresponding tosyl-derivative using the K{sup 18}FF-kryptofix{sub 222} (in CH{sub 3}CN (3 mL) at 85 degrees C for 5 min or D.M.S.O. (600 {mu}L) at 130 degrees C for 5 min). {sup 18}FD.P.A.-714 was then purified using semi preparative X terra reverse phase H.P.L.C., adequately formulated for i.v. injection and was found to be > 95% chemically and radiochemically pure. The total synthesis time was less than 90 min and the specific radioactivities at the end of the radiosynthesis ranged from 1 to 3 Ci/micro-mole. (N.C.)

Diagnostic accuracy of 18F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis

International Nuclear Information System (INIS)

Treglia, Giorgio; Salsano, Marco; Stefanelli, Antonella; Mattoli, Maria Vittoria; Giordano, Alessandro; Bonomo, Lorenzo

2012-01-01

To systematically review and meta-analyse literature data on the diagnostic performance of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) in patients with Ewing sarcoma family tumours (ESFT). PubMed/MEDLINE, Embase and Scopus databases were searched for articles that evaluated FDG-PET and PET/CT in patients with ESFT from inception to 31 May 2011. Studies that fulfilled the three following criteria were included in the systematic review: FDG-PET or PET/CT performed in patients with ESFT; articles about the diagnostic accuracy of FDG-PET and PET/CT; sample size of at least 10 patients with ESFT were included. Studies in which there were sufficient data to reassess sensitivity and specificity of FDG-PET or PET/CT in ESFT were included in the meta-analysis, excluding duplicate publications. Finally, pooled sensitivity, pooled specificity and area under the receiver operating characteristic (ROC) curve of FDG-PET or PET/CT in ESFT were calculated. We found 13 studies comprising a total of 342 patients with ESFT. The main findings of the studies included are presented. The meta-analysis of five selected studies provided these results about FDG-PET and PET/CT in ESFT: pooled sensitivity: 96% (95% confidence interval [CI] 91-99%); pooled specificity: 92% (95% CI 87-96%); area under the ROC curve: 0.97. With regard to the staging and restaging of patients with ESFT, the sensitivity, specificity and accuracy of FDG-PET and PET/CT are high; the combination of FDG-PET or PET/CT with conventional imaging is a valuable tool for the staging and restaging of ESFT and has a relevant impact on the treatment strategy plan. (orig.)

Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

Directory of Open Access Journals (Sweden)

Stef De Lombaerde

2018-01-01

Full Text Available Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET- imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA; a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.. Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group: hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c. and high radiochemical purity (>99%; 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are

Brain tumour imaging with PET: a comparison between [{sup 18}F]fluorodopa and [{sup 11}C]methionine

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Becherer, Alexander; Karanikas, Georgios; Szabo, Monica; Zettinig, Georg; Wadsak, Wolfgang; Kletter, Kurt [Department of Nuclear Medicine, Medical School, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Asenbaum, Susanne [Department of Neurology, Medical School, University of Vienna, Vienna (Austria); Marosi, Christine [Department of Oncology, Medical School, University of Vienna, Vienna (Austria); Henk, Christine; Wunderbaldinger, Patrick [Department of Radiology, Medical School, University of Vienna, Vienna (Austria); Czech, Thomas [Department of Neurosurgery, Medical School, University of Vienna, Vienna (Austria)

2003-11-01

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[{sup 18}F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean{+-}SD), were 2.05{+-}0.91 for MET and 2.04{+-}0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of {sup 18}F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. (orig.)

Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma

Science.gov (United States)

Liu, Fanxiao; Zhang, Qingyu; Zhu, Dezhi; Li, Zhenfeng; Li, Jianmin; Wang, Boim; Zhou, Dongsheng; Dong, Jinlei

2015-01-01

Abstract To investigate the performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature. To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: “positron emission tomography” or “PET,” and “bone tumor” or “bone sarcoma” or “sarcoma.” Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of 18F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4. Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93–98) and 79% (95% CI, 63–90), respectively. For detecting recurrence, the pooled results on an examination-based level were sensitivity 92% (95% CI, 85–97), specificity 93% (95% CI, 88–96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99–17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05–0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86–93), specificity 85% (95% CI, 81–87), PLR 5.16 (95% CI, 2.37–11.25), and NLR 0.15 (95% CI, 0.11–0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of 18F-FDG PET were less complete compared with those of PET/CT. 18F-FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging

Impact of Endoscopic Ultrasonography on 18F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment.

Science.gov (United States)

Hulshoff, J B; Mul, V E M; de Boer, H E M; Noordzij, W; Korteweg, T; van Dullemen, H M; Nagengast, W B; Oppedijk, V; Pierie, J P E N; Plukker, John Th M

2017-07-01

In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography ( 18 F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid 18 F-FDG-PET/CT or 18 F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes.

MicroPET Evaluation of a Hydroxamate-Based MMP Inhibitor, [(18)F]FB-ML5, in a Mouse Model of Cigarette Smoke-Induced Acute Airway Inflammation.

Science.gov (United States)

Matusiak, Nathalie; van Waarde, Aren; Rozeveld, Dennie; van Oosterhout, Antoon J M; Heijink, Irene H; Castelli, Riccardo; Overkleeft, Herman S; Bischoff, Rainer; Dierckx, Rudi A J O; Elsinga, Philip H

2015-10-01

Matrix metalloproteinases (MMPs) are the main proteolytic enzymes involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). A radiolabeled MMP inhibitor, [(18)F]FB-ML5, was prepared, and its in vivo kinetics were tested in a mouse model of pulmonary inflammation. BALB/c mice were exposed for 4 days to cigarette smoke (CS) or air. On the fifth day, a dynamic microPET scan was made with [(18)F]FB-ML5. Standardized uptake values (PET-SUVmean) were 0.19 ± 0.06 in the lungs of CS-exposed mice (n = 6) compared to 0.11 ± 0.03 (n = 5) in air-exposed controls (p FB-ML5.

PET imaging evaluation of [{sup 18}F]DBT-10, a novel radioligand specific to α{sub 7} nicotinic acetylcholine receptors, in nonhuman primates

Energy Technology Data Exchange (ETDEWEB)

Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, 801 Howard Ave, PO Box 208048, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

2016-03-15

Positron emission tomography (PET) radioligands specific to α{sub 7} nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α{sub 7}-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[{sup 18}F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([{sup 18}F]DBT-10), in nonhuman primates. [{sup 18}F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [{sup 18}F]DBT-10 PET, with measurement of [{sup 18}F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α{sub 7}-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [{sup 18}F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V{sub T}/f{sub P}). [{sup 18}F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [{sup 18}F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55 %. Uptake of [{sup 18}F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4 %. No evidence for radiolabeled [{sup 18}F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V{sub T}/f{sub P} values were 193-376 ml/cm{sup 3} across regions, with regional rank order of thalamus > frontal cortex > striatum

Synthesis and evaluation of [[sup 18]F]fluoroprogestins and [[sup 18]F]fluorometoprolol

Energy Technology Data Exchange (ETDEWEB)

De Groot, T J

1993-05-01

The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and [beta][sub 1]-adrenergic ligands are described. Three approaches towards [[sup 18]F]fluorination are investigated. The first method concerns direct S[sub N]2-substitution, the second approach is the opening of an epoxide, and the third approach is [[sup 18]F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [[sup 18]F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[[sup 18]F]fluorinated progestins is discussed. The synthesis of four 21-[[sup 18]F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6[alpha]-[[sup 18]F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled [beta][sub 1]-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[[sup 18]F]fluorometoprolol, the [[sup 18]F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a [beta][sub 1]-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs.

The synthesis of fluorine-18 lomefloxacin and its preliminary use in human studies

International Nuclear Information System (INIS)

Tewson, T.J.; Yang, D.; Wong, G.; Macy, D.; Jesus, O.J. de; Nickles, R.J.; Perlman, S.B.; Taylor, M.; Frank, P.

1996-01-01

Lomefloxacin is a new fluorine-containing antibiotic that has recently been approved for general use. Fluorine-18 lomefloxacin has been prepared by fluoride exchange between fluorine-18 fluoride and lomefloxacin in DMSO. Both time and temperature of the reaction have been optimized and conditions developed for the isolation and purification of the labeled product in a form suitable for oral administration. The exchange reaction provides sufficient labeled material for human studies with pharmacologically relevant quantities of the drug. We have performed preliminary human studies with this compound using positron emission tomography to estimate the tissue distribution of the compound and show the distribution of the compound into the liver and lungs

18F-FDG PET and PET/CT in Burkitt's lymphoma

International Nuclear Information System (INIS)

Karantanis, Dimitrios; Durski, Jolanta M.; Lowe, Val J.; Nathan, Mark A.; Mullan, Brian P.; Georgiou, Evangelos; Johnston, Patrick B.; Wiseman, Gregory A.

2010-01-01

Objective: To explore the value of 18 F fluorodeoxy-glucose (FDG) positron emission tomography (PET) in Burkitt's lymphoma. Methods: All Burkitt's lymphoma patients referred for FDG PET or FDG PET/computed tomography (CT) exams at our institution from June 2003 to June 2006 were included. Selected patients were followed and clinical information was reviewed retrospectively. Results from FDG PET-PET/CT, as blindly reviewed by a consensus of two experienced readers, were compared with the status of the disease as determined by other laboratory, clinical and imaging exams and clinical follow-up. FDG PET-PET/CT results were classified as true positive or negative and false positive or negative. The degree of FDG uptake in the positive lesions was semiquantified as maximum standard uptake value (SUVmax). Results: Fifty-seven FDG PET-PET/CT exams were done in 15 patients. Seven exams were done for initial staging, 8 during and 14 after the completion of therapy, and 28 for disease surveillance. For nodal disease FDG PET-PET/CT was true positive in 8, true negative in 47 and false positive in 2 exams (sensitivity 100%, specificity 96%). For extranodal disease FDG PET-PET/CT was true positive in 6, true negative in 48 and false positive in 3 exams (sensitivity 100%, specificity 94%). The mean SUVmax for the positive nodal lesions was 15.7 (range 6.9-21.7, median 18.5) and for extranodal lesions was 14.2 (range 6.2-24.3, median 12.4). Conclusions: FDG PET-PET/CT is sensitive for the detection of viable disease in Burkitt's lymphoma. Affected areas demonstrated high degree of uptake that was reversible upon successful implementation of treatment.

Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization procedures

International Nuclear Information System (INIS)

Schomburg, A.; Bender, H.; Reichel, C.; Sommer, T.; Ruhlmann, J.; Kozak, B.; Biersack, H.J.

1996-01-01

While the evident advantages of absolute metabolic rate determinations cannot be equalled by static image analysis of fluorine-18 fluorodexyglucose positron emission tomographic (FDG PET) studies, various algorithms for the normalization of static FDG uptake values have been proposed. This study was performed to compare different normalization procedures in terms of dependency on individual patient characteristics. Standardized FDG uptake values (SUVs) were calculated for liver and lung tissue in 126 patients studied with whole-body FDG PET. Uptake values were normalized for total body weight, lean body mass and body surface area. Ranges, means, medians, standard deviations and variation coefficients of these SUV parameters were calculated and their interdependency with total body weight, lean body mass, body surface area, patient height and blood sugar levels was calculated by means of regression analysis. Standardized FDG uptake values normalized for body surface area were clearly superior to SUV parameters normalized for total body weight or lean body mass. Variation and correlation coefficients of body surface area-normalized uptake values were minimal when compared with SUV parameters derived from the other normalization procedures. Normalization for total body weight resulted in uptake values still dependent on body weight and blood sugar levels, while normalization for lean body mass did not eliminate the positive correlation with lean body mass and patient height. It is concluded that normalization of FDG uptake values for body surface area is less dependent on the individual patient characteristics than are FDG uptake values normalized for other parameters, and therefore appears to be preferable for FDG PET studies in oncology. (orig.)

18F-FDG PET brain images as features for Alzheimer classification

Science.gov (United States)

Azmi, M. H.; Saripan, M. I.; Nordin, A. J.; Ahmad Saad, F. F.; Abdul Aziz, S. A.; Wan Adnan, W. A.

2017-08-01

2-Deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) Positron Emission Tomography (PET) imaging offers meaningful information for various types of diseases diagnosis. In Alzheimer's disease (AD), the hypometabolism of glucose which observed on the low intensity voxel in PET image may relate to the onset of the disease. The importance of early detection of AD is inevitable because the resultant brain damage is irreversible. Several statistical analysis and machine learning algorithm have been proposed to investigate the rate and the pattern of the hypometabolism. This study focus on the same aim with further investigation was performed on several hypometabolism pattern. Some pre-processing steps were implemented to standardize the data in order to minimize the effect of resolution and anatomical differences. The features used are the mean voxel intensity within the AD pattern mask, which derived from several z-score and FDR threshold values. The global mean voxel (GMV) and slice-based mean voxel (SbMV) intensity were observed and used as input to the neural network. Several neural network architectures were tested and compared to the nearest neighbour method. The highest accuracy equals to 0.9 and recorded at z-score ≤-1.3 with 1 node neural network architecture (sensitivity=0.81 and specificity=0.95) and at z-score ≤-0.7 with 10 nodes neural network (sensitivity=0.83 and specificity=0.94).

5-tert-Butyl-2-(4'-[{sup 18}F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA{sub A} receptor radioligands

Energy Technology Data Exchange (ETDEWEB)

Li Xuehe; Jung, Yong-Woon; Snyder, Scott E.; Blair, Joseph; Sherman, Philip S.; Desmond, Timothy; Frey, Kirk A. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Kilbourn, Michael R. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States)], E-mail: mkilbour@umich.edu

2008-07-15

As potential new ligands targeting the binding site of {gamma}-aminobutyric acid (GABA) receptor ionophore, trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1, 3-dithiane (1) and cis/trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1,3, 3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities (K{sub i}=6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [{sup 18}F]fluorination. In vivo biodistribution studies with trans-[{sup 18}F]1 and trans-[{sup 18}F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons-medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA{sub A} receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.

Are restrictions to behaviour of patients required following fluorine-18 fluorodeoxyglucose positron emission tomographic studies?

International Nuclear Information System (INIS)

Cronin, B.; Marsden, P.K.; O'Doherty, M.J.

1999-01-01

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose ( 18 FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain 18 FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 μSv h -1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 μSv h -1 MBq -1 ). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 μSv h -1 (0.43, 0.2, 0.08 and 0.03 μSv h -1 MBq -1 ). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 μSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of 18 FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity

18F-fluorodeoxyglucose PET and PET-CT in early detection of cancer recurrent

International Nuclear Information System (INIS)

Xing Yan; Zhao Jinhua

2007-01-01

Early detection of recurrent can improve prognosis and survival of patients with cancer. 18 F- fluorodeoxyglucose( 18 F-FDG) PET can detect metabolic changes before structural changes. The fused imaging provided by PET-CT can precisely localize the foci and demonstrate the complementary roles of functional and anatomic assessments in the diagnosis of cancer recurrence. In addition to the accurate diagnosis and definition of the whole extent of recurrent cancer, 18 F-FDG PET and PET-CT can impact patients management. (authors)

Synthesis of 18F labeled clotrimazole derivatives as a potential PET imaging agent

International Nuclear Information System (INIS)

Jung, Soon Jae; Kim, In Jong; Park, Jeong Hoon; Lee, Heung Nae; Kim, Sang Wook; Hur, Min Goo; Choi, Sang Moo; Yang, Seung Dae; Yu, Kook Hyun

2010-01-01

Clotrimazole [1- -1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [ 18 F]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [ 18 ]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/K 2 CO 3 for 10 min at 80 .deg. C. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove 18 F - . The [ 18 ]F-clotrimazole derivatives were synthesized with a 20 ∼ 25% yield. In the radiofluoriantion step, we used acetonitrile and DMSO as a solvent and observed a higher at the acetonitrile (25%) reaction compared with the DMSO reaction (5%)

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

Science.gov (United States)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

2016-01-01

Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

Diagnostic accuracy of {sup 18}F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio [Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Institute of Nuclear Medicine, Positron Emission Tomography Centre, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Salsano, Marco; Stefanelli, Antonella; Mattoli, Maria Vittoria; Giordano, Alessandro [Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy); Bonomo, Lorenzo [Institute of Radiology, Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Rome (Italy)

2012-03-15

To systematically review and meta-analyse literature data on the diagnostic performance of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) in patients with Ewing sarcoma family tumours (ESFT). PubMed/MEDLINE, Embase and Scopus databases were searched for articles that evaluated FDG-PET and PET/CT in patients with ESFT from inception to 31 May 2011. Studies that fulfilled the three following criteria were included in the systematic review: FDG-PET or PET/CT performed in patients with ESFT; articles about the diagnostic accuracy of FDG-PET and PET/CT; sample size of at least 10 patients with ESFT were included. Studies in which there were sufficient data to reassess sensitivity and specificity of FDG-PET or PET/CT in ESFT were included in the meta-analysis, excluding duplicate publications. Finally, pooled sensitivity, pooled specificity and area under the receiver operating characteristic (ROC) curve of FDG-PET or PET/CT in ESFT were calculated. We found 13 studies comprising a total of 342 patients with ESFT. The main findings of the studies included are presented. The meta-analysis of five selected studies provided these results about FDG-PET and PET/CT in ESFT: pooled sensitivity: 96% (95% confidence interval [CI] 91-99%); pooled specificity: 92% (95% CI 87-96%); area under the ROC curve: 0.97. With regard to the staging and restaging of patients with ESFT, the sensitivity, specificity and accuracy of FDG-PET and PET/CT are high; the combination of FDG-PET or PET/CT with conventional imaging is a valuable tool for the staging and restaging of ESFT and has a relevant impact on the treatment strategy plan. (orig.)

{sup 18}F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis..; La TEP au {sup 18}F-FDG dans la pathologie inflammatoire et infectieuse: intestinale, prothetique, fibrose, sarcoidose, tuberculose..

Energy Technology Data Exchange (ETDEWEB)

Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C. [Hospital Universitari de Bellvitge, Service TEP-Centre IDI, Services de Medecine Interne, Barcelone (Spain)

2008-10-15

Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, {sup 68}Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ({sup 18}F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. {sup 18}F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). {sup 18}F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. {sup 18}F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of {sup 18}F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection.

Clinical Application of F-18 FDG PET (PET/CT) in Malignancy of Unknown Origin

International Nuclear Information System (INIS)

Kim, Byung Il

2008-01-01

Diagnosis of primary origin site in the management of malignancy of unknown origin (MUO) is the most important issue. According to the histopathologic subtype of primary lesion, specialized treatment can be given and survival gain is expected. F-18 FDG PET (PET/CT) has been estimated as useful in detection of primary lesion with high sensitivity and moderate specificity. F-18 FDG PET (PET/CT) study before conventional studies is also recommended because it has high diagnostic performance compared to conventional studies. Although there has few data, F-18 FDG PET (PET/CT) is expected to be useful in diagnosis of recurrence, restaging, evaluation of treatment effect, considering that PET (PET/CT) has been reported as useful in other malignancies

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

Science.gov (United States)

Wanek, Thomas; Kreis, Katharina; Križková, Petra; Schweifer, Anna; Denk, Christoph; Stanek, Johann; Mairinger, Severin; Filip, Thomas; Sauberer, Michael; Edelhofer, Patricia; Traxl, Alexander; Muchitsch, Viktoria E; Mereiter, Kurt; Hammerschmidt, Friedrich; Cass, Carol E; Damaraju, Vijaya L; Langer, Oliver; Kuntner, Claudia

2016-11-01

Positron emission tomography (PET) using fluorine-18 ( 18 F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[ 18 F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[ 18 F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [ 18 F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [ 18 F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[ 18 F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[ 18 F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13±0.22 (n=4) at 2h after administration of β-[ 18 F]1. In ex vivo autoradiography experiments β-[ 18 F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[ 18 F]1 shows potential as PET hypoxia radiotracer which merits further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel facile method of labeling octreotide with (18)F-fluorine.

Science.gov (United States)

Laverman, Peter; McBride, William J; Sharkey, Robert M; Eek, Annemarie; Joosten, Lieke; Oyen, Wim J G; Goldenberg, David M; Boerman, Otto C

2010-03-01

Several methods have been developed to label peptides with (18)F. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH(+) 1305) [IMP466]) with (18)F. Octreotide was conjugated with the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In addition, small-animal PET/CT images were acquired. IMP466 was labeled with Al(18)F in a single step with 50% yield. The labeled product was purified by high-performance liquid chromatography to remove unbound Al(18)F and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4 h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N-morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer. The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar to that of (18)F-IMP466. (18)F

Clinical Usefulness of 18F-fluoride Bone PET

International Nuclear Information System (INIS)

Kang, Ji Yeon; Lee, Won Woo; Lee, Byung Chul; Kim, Sang Eun; So, Young

2010-01-01

18 F-fluoride bone positron emission tomography (PET) has been reported as a useful bone imaging modality. However, no clinical bone PET study had been performed previously in Korea. The authors investigated the usefulness of 18 F-fluoride bone PET in Korean patients with malignant or benign bone disease. Eighteen consecutive patients (eight women, ten men; mean age, 55±12 years) who had undergone 18 F-fluoride bone PET for the evaluation of bone metastasis (n=13) or benign bone lesions (n=5) were included. The interpretation of bone lesions on 18 F-fluoride bone PET was determined by consensus of two nuclear medicine physicians, and final results were confirmed using combination of all imaging studies and/or clinical follow-up. The analysis was performed on the basis of lesion group. Thirteen patients with malignant disease had 15 lesion groups, among which seven were confirmed as metastatic bone lesions and eight were confirmed as non-metastatic lesions. 18 F-fluoride bone PET correctly identified six of seven metastatic lesions (sensitivity, 86%), and seven of eight non-metastatic lesions (specificity, 88%). On the other hand, five patients with benign conditions had five bone lesion groups; four were confirmed as benign bone diseases and the other one was confirmed as not a bone lesion. 18 F-fluoride bone PET showed correct results in all the five lesion groups. 18 F-fluoride bone PET showed promising potential for bone imaging in Korean patients with malignant diseases as well as with various benign bone conditions. Therefore, further studies are required on the diagnostic performance and cost-effectiveness of 18 F-fluoride bone PET.

Synthesis of [18F]-labelled nebivolol as a β1-adrenergic receptor antagonist for PET imaging agent

International Nuclear Information System (INIS)

Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae; Chang, Dong Jo

2017-01-01

Selective β 1 -agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β 1 -antagonists including nebivolol have high binding affinity on β 1 -adrenergic receptor, not β 2 -receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β 1 -blockers in clinically used β 1 - blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β 1 -blocker. Nebivolol is C 2 -symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of 18 F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for 18 F-aromatic substitution, was synthesized in moderate yield which was readily subjected to 18 F-aromatic substitution to give 18 F-labelled nebivolol

Comparison of two synthetic methods to obtain [18F] N-(2-aminoethyl)-5-fluoropyridine-2-carboxamide, a potential MAO-B imaging tracer for PET

International Nuclear Information System (INIS)

Beer, H.-F.; Haeberli, M.; Ametamey, S.; Schubiger, P.A.

1995-01-01

The compound Ro 19-6327, N-(2-aminoethyl)-5-chloropyridine-2-carboxamide, is known to inhibit reversibly and site specifically the enzyme monoamine oxidase B (MAO-B). The 123 I-labelled iodo-analogue N-(2-aminoethyl)-5-iodopyridine-2-carboxamide (Ro 43-0463) was investigated successfully in human volunteers by means of SPET (Single Photon Emission Tomography). We developed therefore the synthesis and radiolabelling of the corresponding fluoro-analogue N-(2-aminoethyl)-5-fluoropyridine-2-carboxamide with 18 F in order to carry out PET (Positron Emission Tomography) investigations of MAO-B related neuropsychiatric diseases. For this purpose two synthetic approaches leading to the electrophilic and the nucleophilic methods of 18 F radiolabelling were undertaken. The nucleophilic approach appeared to be superior when factors such as precursor synthesis, beam time, specific activity and radiochemical purity of the product are considered. (author)

18F-fluorination by crown ether-metal fluoride

International Nuclear Information System (INIS)

Irie, T.; Fukushi, K.; Ido, T.; Kasida, Y.; Nozaki, T.

1982-01-01

18 F-Fluorination by ''naked'' 18 F - anion produced by complexing anhydrous K 18 F, which was prepared from aqueous 18 F, with 18 -Crown-6 was described for preparing 18 F-21-fluoroprogesterone. In order to find out optimum conditions in this labelling method, various factors were investigated such as the solubility of KF in organic solvents containing 18 -Crown-6 and its reactivity for the nucleophilic displacement of 21-mesylate of progesterone. Chloroform was a good solvent in solubilization of KF and its reactivity. Problems in this labelling procedure were also examined, such as a supporter for transferring the labelled anhydrous K 18 F and reaction vessels. Use of a Teflon reaction vessel resulted in a good radiochemical yield based on the starting activity of $ 18 water. (author)

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

Science.gov (United States)

Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

1999-11-01

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.

Impacts of biological and procedural factors on semiquantification uptake value of liver in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging.

Science.gov (United States)

Mahmud, Mohd Hafizi; Nordin, Abdul Jalil; Ahmad Saad, Fathinul Fikri; Azman, Ahmad Zaid Fattah

2015-10-01

Increased metabolic activity of fluorodeoxyglucose (FDG) in tissue is not only resulting of pathological uptake, but due to physiological uptake as well. This study aimed to determine the impacts of biological and procedural factors on FDG uptake of liver in whole body positron emission tomography/computed tomography (PET/CT) imaging. Whole body fluorine-18 ((18)F) FDG PET/CT scans of 51 oncology patients have been reviewed. Maximum standardized uptake value (SUVmax) of lesion-free liver was quantified in each patient. Pearson correlation was performed to determine the association between the factors of age, body mass index (BMI), blood glucose level, FDG dose and incubation period and liver SUVmax. Multivariate regression analysis was established to determine the significant factors that best predicted the liver SUVmax. Then the subjects were dichotomised into four BMI groups. Analysis of variance (ANOVA) was established for mean difference of SUVmax of liver between those BMI groups. BMI and incubation period were significantly associated with liver SUVmax. These factors were accounted for 29.6% of the liver SUVmax variance. Statistically significant differences were observed in the mean SUVmax of liver among those BMI groups (Pvalue for physiological liver SUVmax as a reference standard for different BMI of patients in PET/CT interpretation and use a standard protocol for incubation period of patient to reduce variation in physiological FDG uptake of liver in PET/CT study.

The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

Energy Technology Data Exchange (ETDEWEB)

Ryoo, Baek Yeol; Kang, Yoon Koo

1998-12-01

The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary.

The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

International Nuclear Information System (INIS)

Ryoo, Baek Yeol; Kang, Yoon Koo

1998-12-01

The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary

Synthesis and Biological Evaluation of an 18Fluorine-Labeled COX Inhibitor—[18F]Fluorooctyl Fenbufen Amide—For Imaging of Brain Tumors

Directory of Open Access Journals (Sweden)

Ying-Cheng Huang

2016-03-01

Full Text Available Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts2O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [18F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [18F]F− (212 mCi via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS based on decay-corrected calculations. Ex-vivo analysis of [18F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [18F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments.

Positron Emission Tomography Imaging Using Radiolabeled Inorganic Nanomaterials

Science.gov (United States)

Sun, Xiaolian; Cai, Weibo; Chen, Xiaoyuan

2015-01-01

CONSPECTUS Positron emission tomography (PET) is a radionuclide imaging technology that plays an important role in preclinical and clinical research. With administration of a small amount of radiotracer, PET imaging can provide a noninvasive, highly sensitive, and quantitative readout of its organ/tissue targeting efficiency and pharmacokinetics. Various radiotracers have been designed to target specific molecular events. Compared with antibodies, proteins, peptides, and other biologically relevant molecules, nanoparticles represent a new frontier in molecular imaging probe design, enabling the attachment of different imaging modalities, targeting ligands, and therapeutic payloads in a single vector. We introduce the radiolabeled nanoparticle platforms that we and others have developed. Due to the fundamental differences in the various nanoparticles and radioisotopes, most radiolabeling methods are designed case-by-case. We focus on some general rules about selecting appropriate isotopes for given types of nanoparticles, as well as adjusting the labeling strategies according to specific applications. We classified these radiolabeling methods into four categories: (1) complexation reaction of radiometal ions with chelators via coordination chemistry; (2) direct bombardment of nanoparticles via hadronic projectiles; (3) synthesis of nanoparticles using a mixture of radioactive and nonradioactive precursors; (4) chelator-free postsynthetic radiolabeling. Method 1 is generally applicable to different nanomaterials as long as the surface chemistry is well-designed. However, the addition of chelators brings concerns of possible changes to the physicochemical properties of nanomaterials and detachment of the radiometal. Methods 2 and 3 have improved radiochemical stability. The applications are, however, limited by the possible damage to the nanocomponent caused by the proton beams (method 2) and harsh synthetic conditions (method 3). Method 4 is still in its infancy

Evaluation of gross tumor size using CT, 18F-FDG PET, integrated 18F-FDG PET/CT and pathological analysis in non-small cell lung cancer

International Nuclear Information System (INIS)

Yu Huiming; Liu Yunfang; Hou Ming; Liu Jie; Li Xiaonan; Yu Jinming

2009-01-01

Purpose: The correlation of gross tumor sizes between combined 18 F-FDG PET/CT images and macroscopic surgical samples has not yet been studied in detail. In the present study, we compared CT, 18 F-FDG PET and combined 18 F-FDG PET/CT for the delineation of gross tumor volume (GTV) and validated the results through examination of the macroscopic surgical specimen. Methods: Fifty-two operable non-small cell lung cancer (NSCLC) patients had integrated 18 F-FDG PET/CT scans preoperatively and pathological examination post-operation. Four separate maximal tumor sizes at X (lateral direction), Y (ventro-dorsal direction) and Z (cranio-caudal direction) axis were measured on 18 F-FDG PET, CT, combined 18 F-FDG PET/CT and surgical specimen, respectively. Linear regression was calculated for each of the three imaging measurements versus pathological measurement. Results: No significant differences were observed among the tumor sizes measured by three images and pathological method. Compared with pathological measurement, CT size at X, Y, Z axis was larger, whereas combined 18 F-FDG PET/CT and 18 F-FDG PET size were smaller. Combined 18 F-FDG PET/CT size was more similar to the pathological size than that of 18 F-FDG PET or CT. Results of linear regressions showed that integrated 18 F-FDG PET/CT was the most accurate modality in measuring the size of cancer. Conclusions: 18 F-FDG PET/CT correlates more faithfully with pathological findings than 18 F-FDG PET or CT. Integrated 18 F-FDG PET/CT is an effective tool to define the target of GTV in radiotherapy.

Impact of EBUS-TBNA on PET-CT Imaging of Mediastinal Nodes

DEFF Research Database (Denmark)

Sivapalan, Pradeesh; Naur, Therese Maria Henriette; Colella, Sara

2017-01-01

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with fluorine-18-fluorodeoxyglucose has a high sensitivity in detecting malignancy in patients suspected of lung cancer but a low specificity as inflammatory reactions can also result in metabolic activity. Furthermore, it is a......BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with fluorine-18-fluorodeoxyglucose has a high sensitivity in detecting malignancy in patients suspected of lung cancer but a low specificity as inflammatory reactions can also result in metabolic activity. Furthermore......, it is assumed that invasive pulmonary procedures with biopsies from benign lesions can induce metabolic activity resulting in false-positive results. However, this hypothesis lacks solid evidence. We aimed to evaluate how often endobronchial ultrasound (EBUS) with biopsies from benign lesions are followed...

Synthesis of Fluorine-18 Labeled Glucose-Lys-Arg-Gly-Asp-D-Phe as a Potential Tumor Imaging Agent

International Nuclear Information System (INIS)

Lee, Kyo Chul; Kim, Ji Sun; Sung, Hyun Ju; Jung, Jae Ho; An, Gwang Il; Chi, Dae Yoon; Lee, Byung Chul; Moon, Byung Seok; Choi, Tae Hyun; Chuna, Kwon Soo

2005-01-01

The α v β 3 integrin is an important receptor affecting tumor growth, metastatic potential on proliferating endothelial cells as well as on tumor cells of various origin, tumor-induced angiogenesis could be blocked by antagonizing the α v β 3 integrin with RGD. Therefore, α v β 3 integrin is a target for angiogenesis imaging that might be useful in assessing tumor-induced angiogenesis and identifying tumor metastasis. To design potent radiotracer for imaging angiogenesis containing a cRGD moiety should include low hepatic uptake in vivo. Tripeptide Arg-Gly-Asp (RGD), naturally existed in extracellular matrix proteins, is known to be the primary binding site of the α v β 3 integrin. The imaging of α v β 3 receptor expression will give the information of the metastatic ability of the tumor which is not available by [ 18 F]FDG. Our interest in developing new radiopharmaceuticals for in vivo visualization of angiogenesis has led us to synthesize derivatives of cRGD (cyclic arginineglycine-aspartic acid) that contains glucose moiety. Because sugar-protein interaction is a key step in metastasis and angiogenesis, it has also been proposed to play an intriguing role in imaging of tumor. We designed and synthesized two fluorine-18 labeled RGD glycopeptides . N-fluorobenzyl-diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([ 18 F]fluorobenzyl-glucose-KRGDf, and Nfluorobenzoyl- diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([ 18 F]fluorobenzoyl-glucose-KRGDf, from same precursor as a diagnostic tumor imaging agent for positron emission tomography (PET). Fluorine-18 labeled cRGD glycopeptides were prepared using two different simple labeling methods: one is reductive alkylation of an amine with [ 18 F]fluorobenzaldehyde and the other is amide condensation with [ 18 F]fluorobenzoic acid

FDOPA-(18F: a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union

Directory of Open Access Journals (Sweden)

Yanna-Marina Chevalme

2007-09-01

Full Text Available Positron emission tomography (PET and its recent update PET/CT are very effective diagnostic tools for non-invasive imaging of metabolic or functional disorders in target tissues. The clinical usefulness of fluorodeoxyglucose-(18F (FDG has been now widely accepted. Recently, the clinical usefulness of fluoroDOPA-(18F or FDOPA, an aminoacid labelled with the same positron emitter fluorine-18, has been evaluated and recognised in France and subsequently in several EU countries. FDOPA is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. The present article summarises the body of evidence that led the French Medicines Agency (AFSSAPS to grant a marketing authorisation to IASOdopa, a commercial preparation of FDOPA. Brief case reports and figures illustrate the diagnostic performance of FDOPA PET or PET/CT in the different settings that are currently approved in oncology.Tomografia por emissão de positrons (PET e sua recente atualização PET/CT são ferramentas de diagnóstico muito eficientes para imagens não invasivas de desordens metabólicas ou funcionais em tecido alvo. A utilidade clínica da fluordesoxiglicose-(18F(FDG tem sido agora largamente aceita. Recentemente, a utilidade clinica de fluoroDOPA-(18F ou FDOPA, um aminoácido marcado com o mesmo emissor de pósitron, flúor-18, tem sido avaliado e reconhecido na França e subsequentemente em alguns países da União Européia. FDOPA é o radiofármaco para diagnóstico em PET, o qual tem sido usado por décadas para obtenção de imagens da perda de neurônios dopaminérgicos na doença de Parkinson e, mais recentemente, para identificar inicialmente o estágio e a reavaliação de tumores neuroendócrinos e para a pesquisa da recorrência de glioma viável. O presente artigo resume o conjunto

[F-18]FDG imaging of head and neck tumors: comparison of hybrid PET, dedicated PET and CT

International Nuclear Information System (INIS)

Dresel, S.; Brinkbaeumer, K.; Schmid, R.; Poepperl, G.; Hahn, K.; Szeimies, U.

2001-01-01

Aim: Aim of the study was to evaluate [F-18]FDG imaging of head and neck tumors using a Hybrid-PET device of the 2nd or 3rd generation. Examinations were compared to dedicated PET and Spiral-CT. Methods: 54 patients suffering from head and neck tumors were examined using dedicated PET and Hybrid-PET after injection of 185-350 MBq [F-18]FDG. Examinations were carried out on the dedicated PET first followed by a scan on the Hybrid-PET. Dedicated PET was acquired in 3D mode, Hybrid-PET was performed in list mode using an axial filter. Reconstruction of data was performed iteratively on both, dedicated PET and Hybrid-PET. All patients received a CT scan in multislice technique. All finding have been verified by the goldstandard histology or in case of negative histology by follow up. Results: Using dedicated PET the primary or recurrent lesion was correctly diagnosed in 47/48 patients, using Hybrid-PET in 46/48 patients and using CT in 25/48 patients. Metastatic disease in cervical lymph nodes was diagnosed in 17/18 patients with dedicated PET, in 16/18 patients with Hybrid-PET and in 15/18 with CT. False positive results with regard to lymph node metastasis were seen with one patient for dedicated PET and Hybrid-PET, respectively, and with 18 patients for CT. In a total of 11 patients unknown metastastic lesions were seen with dedicated PET and with Hybrid-PET elsewhere in the body. Additional malignant disease other than the head and neck tumor was found in 4 patients. Conclusion: Using Hybrid-PET for [F-18]FDG imaging reveals a loss of sensitivity and specificity of about 1-5% as compared to dedicated PET in head and neck tumors. [F-18]FDG PET with both, dedicated PET and Hybrid-PET is superior to CT in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement. (orig.) [de

Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

Science.gov (United States)

Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

2017-05-01

Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.

Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

Science.gov (United States)

Kaneuchi, Yoichi; Hakozaki, Michiyuki; Yamada, Hitoshi; Hasegawa, Osamu; Tajino, Takahiro; Konno, Shinichi

2016-01-01

We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

Fluorine-18 labelling of a novel series of chimeric, mdm2 oncogene targeting, peptide-pna oligomers using [18F]FPyME

International Nuclear Information System (INIS)

Kuhnast, B.; Hinnen, F.; Boisgard, R.; Tavitian, B.; Dolle, F.; Nielsen, P.

2011-01-01

Complete text of publication follows: Peptide nucleic acids (PNAs) form a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double stranded DNA, where the deoxyribose phosphate backbone of original DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while retaining the nucleobases of DNA. PNAs have already showed promising therapeutic potential as antisense and anti-gene agents and are inspiring the development of a variety of research and diagnostic assays, including their use as imaging tools. Within our intensive programs of development of oligonucleotide-based probes for PET-imaging, a novel series of chimeric peptide-PNA oligomers has been designed as complementary antisense probes targeting a specific 15-base sequence located at the intron-exon junction of the pre-mRNA of the murine double minute (mdm2) oncogene. This gene codes for a p53 interacting protein that represses p53 transcriptional activity, and appears to be over expressed in several tumor types including soft tissue sarcomas and osteosarcomas as well as breast tumors. For in vivo 3D-imaging purposes, all oligomers include a cysteine thus providing a sulfhydryl function permitting prosthetic conjugation with maleimide-based reagents such as AlexaFluor680 R (AF680) for optical fluorescence imaging and [ 18 F]FPyME (1-[3-(2-[ 18 F]fluoropyridin-3-yloxy)propyl]pyrrole-2, 5-dione), a prosthetic reagent labeled with the positron-emitter fluorine-18 for PET imaging, which latter work is presented herein. Methods: [ 18 F]FPyME was prepared using a three-step radiochemical pathway already reported and includes an HPLC-purification (semi-preparative SiO 2 Zorbax R Rx-SIL, Hewlett Packard). [ 18 F]FPyME was conjugated with the peptide-PNA oligomers (PNA3132, PNA3133, and PNA3135, 0.25-0.30 micro-moles) in 1/9 (v:v) mixture (1 mL) of DMSO and 0.1 M aq. PBS (pH 8) at room temperature for 15 min. The [ 18 F]FPyME-conjugated products (c-[ 18 F

18F-FDOPA PET/CT imaging of insulinoma revisited

International Nuclear Information System (INIS)

Imperiale, Alessio; Namer, Izzie-Jacques; Sebag, Frederic; Vix, Michel; Castinetti, Frederic; Kessler, Laurence; Moreau, Francois; Bachellier, Philippe; Guillet, Benjamin; Mundler, Olivier; Taieb, David

2015-01-01

18 F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to 18 F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with 18 F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using 18 F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18 F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after 18 F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, 18 F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All 18 F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted 18 F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final

Fluorine-18-fluorocholine PET/CT parameters predictive for hematological toxicity to radium-223 therapy in castrate-resistant prostate cancer patients with bone metastases: a pilot study.

Science.gov (United States)

Vija Racaru, Lavinia; Sinigaglia, Mathieu; Kanoun, Salim; Ben Bouallègue, Fayçal; Tal, Ilan; Brillouet, Sévérine; Bauriaud-Mallet, Mathilde; Zerdoud, Slimane; Dierickx, Lawrence; Vallot, Delphine; Caselles, Olivier; Gabiache, Erwan; Pascal, Pierre; Courbon, Frederic

2018-05-21

This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra. Bone metastatic disease was quantified on the basis of the maximum standardized uptake value (SUV), total lesion activity (TLA=MBTV×SUVmean), or MBTV/height (MBTV/H) and TLA/H. F-FCH PET/CT bone tumor burden and activity were analyzed to identify which parameters could predict hematological toxicity [on hemoglobin (Hb), platelets (PLTs), and lymphocytes] while on Ra therapy. Pearson's correlation was used to identify the correlations between age, prostate-specific antigen, and F-FCH PET parameters. MBTV ranged from 75 to 1259 cm (median: 392 cm). TLA ranged from 342 to 7198 cm (median: 1853 cm). Patients benefited from two to six cycles of Ra (n=56 cycles in total). At the end of Ra therapy, five of the 15 (33%) patients presented grade 2/3 toxicity on Hb and lymphocytes, whereas three of the 15 (20%) patients presented grade 2/3 PLT toxicity.Age was correlated negatively with both MBTV (r=-0.612, P=0.015) and TLA (r=-0.596, P=0.018). TLA, TLA/H, and MBTV/H predicted hematological toxicity on Hb, whereas TLA/H and MBTV/H predicted toxicity on PLTs at the end of Ra cycles. Receiver operating characteristic curve analysis allowed to define the cutoffs for MBTV (915 cm) and TLA (4198 cm) predictive for PLT toxicity, with an accuracy of 0.92 and 0.99. Tumor bone burden calculation is feasible with F-FCH PET/CT with freely available open-source software. In this pilot study, baseline F-FCH PET/CT markers (TLA, MBTV) have shown abilities to predict Hb and PLT toxicity after Ra therapy and could be explored for

Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

International Nuclear Information System (INIS)

Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

2010-01-01

Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

N-(4-F-18-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes

NARCIS (Netherlands)

Di Gialleonardo, Valentina; Signore, Alberto; Glaudemans, Andor W. J. M.; Dierckx, Rudi A. J. O.; De Vries, Erik F. J.

Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the

Peripheral metabolism of [18F]FDDNP and cerebral uptake of its labelled metabolites

International Nuclear Information System (INIS)

Luurtsema, Gert; Schuit, Robert C.; Takkenkamp, Kevin; Lubberink, Mark; Hendrikse, N. Harry; Windhorst, Albert D.; Molthoff, Carla F.M.; Tolboom, Nelleke; Berckel, Bart N.M. van; Lammertsma, Adriaan A.

2008-01-01

[ 18 F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [ 18 F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [ 18 F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar 18 F-labelled fragments, probably formed from N-dealkylation of [ 18 F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake

Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

DEFF Research Database (Denmark)

Jensen, Mette Munk; Kjaer, Andreas

2015-01-01

treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can......Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response...

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [68Ga]Ga- and [18F]AlF-NOTA-Siglec-9

Directory of Open Access Journals (Sweden)

Olli Moisio

2018-01-01

Full Text Available Amino acid residues 283–297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9 form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1. VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET. Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA-conjugated Siglec-9 has been evaluated extensively for this purpose. Here, we explored two alternative strategies for radiolabeling Siglec-9 peptide using a 1,4,7-triazacyclononane-triacetic acid (NOTA-chelator to bind [68Ga]Ga or [18F]AlF. The radioligands were evaluated by in vivo PET imaging and ex vivo γ-counting of turpentine-induced sterile skin/muscle inflammation in Sprague-Dawley rats. Both tracers showed clear accumulation in the inflamed tissues. The whole-body biodistribution patterns of the tracers were similar.

18F-FDG hybrid PET in patients with suspected spondylitis

International Nuclear Information System (INIS)

Gratz, S.; Behr, T.M.; Behe, M.; Doerner, J.; Fischer, U.; Grabbe, E.; Altenvoerde, G.; Meller, J.; Becker, W.

2002-01-01

This study investigated the value of fluorine-18 2'-deoxy-2-fluoro-D-glucose (FDG) imaging with a double-headed gamma camera operated in coincidence (hybrid PET) detection mode in patients with suspected spondylitis. Comparison was made with conventional nuclear medicine imaging modalities and magnetic resonance imaging (MRI). Sixteen patients with suspected spondylitis (nine male, seven female, mean age 59 years) prospectively underwent FDG hybrid PET (296 MBq) and MRI. For intra-individual comparison, the patients were also imaged with technetium-99m methylene diphosphonate (MDP) (555 MBq) (n=13) and/or gallium-67 citrate (185 MBq) (n=11). For FDG hybrid PET, two or three transverse scans were performed. Ratios of infected (target) to non-infected (background) (T/B) vertebral bodies were calculated. MR images were obtained of the region of interest. Patients found positive for spondylitis with MRI and/or FDG hybrid PET underwent surgical intervention and histological grading of the individual infected foci. Twelve out of 16 patients were found to be positive for spondylitis. Independent of the grade of infection and the location in the spine, all known infected vertebrae (n=23, 9 thoracic, 12 lumbar, 2 sacral) were detected by FDG hybrid PET. T/B ratios higher than 1.45±0.05 (at 1 h p.i.) were indicative of infectious disease, whereas ratios below this value were found in cases of degenerative change. FDG hybrid PET was superior to MRI in patients who had a history of surgery and suffered from a high-grade infection in combination with paravertebral abscess formation (n=2; further computed tomography was needed) and in those with low-grade spondylitis (n=2, no oedema) or discitis (n=2, mild oedema). False-positive 67 Ga citrate images (n=5: 2 spondylodiscitis, 1 aortitis, 1 pleuritis, 1 pulmonary tuberculosis) and 99m Tc-MDP SPET (n=4: 1 osteoporosis, 2 spondylodiscitis, 1 fracture) were equally well detected by FDG hybrid PET and MRI. No diagnostic problems

Radiolabeling of liposomes and polymeric micelles with PET-isotopes

DEFF Research Database (Denmark)

Jensen, Andreas Tue Ingemann

as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent‐like copolymers......This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete......‐life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were...

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

Science.gov (United States)

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Correlation between apparent diffusion coefficients and standardized uptake values in hybrid {sup 18}F-FDG PET/MR: Preliminary results in rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Jeong, Ju Hye [Dept. of Nuclear Medicine, Kyungpook National University Hospital, Daegu (Korea, Republic of); Cho, Ihn Ho; Chun, Kyung Ah; Kong, Eun Jung; Kwon, Sang Don; Kim, Jae Hwang [Yeungnam University Hospital, Daegu (Korea, Republic of)

2016-06-15

Fluorine-18-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) share the same role in clinical oncology and it is feasible to obtain the standardized uptake value (SUV) and apparent diffusion coefficient (ADC) simultaneously by emerging the hybrid positron emission tomography/magnetic resonance (PET/MR). This study investigated the correlation between the ADCs of rectal cancer lesions and their SUVs derived from hybrid PET/MR. Nine patients with histologically proven rectal adenocarcinoma (5 men, 4 women; mean age, 70 ± 15.91 years) underwent torso {sup 18}F-FDG PET/CT and regional hybrid {sup 18}F-FDG PET/MR sequentially. A fixed threshold value of 40 % of maximum uptake was used to determine tumor volume of interest (VOI) on PET image; SUV{sub max}, SUV{sub peak}, and SUV{sub mean} were calculated automatically. A single freehand region of interest (ROI) was drawn on high b-value (b1000) DWI image and copied to corresponding ADC map to determine the ADCmean of rectal cancer lesion. Spearman'rank correlation coefficient (ρ) was calculated to determine the correlation between SUVs and ADC values. SUV{sub max}, SUV{sub peak}, and SUV{sub mean} derived by hybrid PET/MR were 12.35 ± 4.66 (mean ± standard deviation), 9.66  ± 3.15 and 7.41 ± 2.54, respectively. The ADCmean value of rectal cancer lesions was 1.02 ± 0.08 × 10{sup -3}mm{sup 2}/s. ADCmean was significantly and inversely correlated with SUV values (SUV{sub max}, ρ = -0.95, p < 0.001; SUV{sub peak}, ρ = -0.93, p < 0.001; SUV{sub mean}, ρ = -0.91, p = 0.001). This preliminary hybrid PET/MR study demonstrates a significant inverse correlation exists between metabolic activity on {sup 18}F-FDG PET and water diffusion on DWI in rectal cancer.

Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI.

Science.gov (United States)

da Silva, N A; Lohmann, P; Fairney, J; Magill, A W; Oros Peusquens, A-M; Choi, C-H; Stirnberg, R; Stoffels, G; Galldiks, N; Golay, X; Langen, K-J; Jon Shah, N

2018-06-01

PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET). Eight patients with gliomas were investigated simultaneously with 18 F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B 1 average power of 1μT. B 0 field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTR asym ) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test. A tumour-to-brain ratio derived from APT# and 18 F-FET presented no significant differences, and no correlation was found between APT# and 18 F-FET PET data. The distance between local hot spot APT# and 18 F-FET were different (average 20 ± 13 mm, range 4-45 mm). For the first time, CEST images were compared with 18 F-FET in a simultaneous MR-PET measurement. Imaging findings derived from 18 F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.

Re(CO)3([18F]FEDA), a novel 18F PET renal tracer: Radiosynthesis and preclinical evaluation.

Science.gov (United States)

Lipowska, Malgorzata; Jarkas, Nashwa; Voll, Ronald J; Nye, Jonathon A; Klenc, Jeffrey; Goodman, Mark M; Taylor, Andrew T

2018-03-01

Our previous work demonstrated that the 99m Tc renal tracer, 99m Tc(CO) 3 (FEDA) ( 99m Tc-1), has a rapid clearance comparable in rats to that of 131 I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99m Tc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18 F renal imaging agent, Re(CO) 3 ([ 18 F]FEDA) ( 18 F-1). Our goal was to develop an efficient one-step method for the preparation of 18 F-1 and to compare its pharmacokinetic properties with those of 131 I-OIH in rats. 18 F-1 was prepared by the nucleophilic 18 F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131 I-OIH as an internal control and by dynamic PET/CT imaging. Plasma protein binding (PPB) and erythrocyte uptake (RCB) were determined and the urine was analyzed for metabolites. 18 F-1 was efficiently prepared as a single species with high radiochemical purity (>99%) and it displayed high radiochemical stability in vitro and in vivo. PPB was 87% and RCB was 21%. Biodistribution studies confirmed rapid renal extraction and high specificity for renal excretion, comparable to that of 131 I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of 131 I-OIH, was 92% and 95% at 10 and 60 min, respectively. All other organs (heart, spleen, lungs) showed a negligible tracer uptake (F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [ 18 F]fluoride. 18 F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of 131 I-OIH and high in vivo radiochemical stability. Not only is 18 F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous 18 F/ 99m Tc renal imaging agents with almost identical structures and comparable

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

International Nuclear Information System (INIS)

Ebenhan, Thomas; Chadwick, Nicholas; Sathekge, Mike M.; Govender, Patrick; Govender, Thavendran; Kruger, Hendrik G.; Marjanovic-Painter, Biljana; Zeevaart, Jan Rijn

2014-01-01

Introduction: Human antimicrobial peptides are of interest for the development of positron emission tomography (PET) tracers as they exhibit desirable characteristics that make them good candidates for targeting vectors. Due to their natural role in the innate immune system they selectively bind to pathogenic bacteria and yeast, whilst remaining minimally immunogenic and cytotoxic to humans. Research into ubiquicidin (UBI)-based tracers has focused on 99m Tc as a radionuclide, however, the use of bi-functional chelators such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), in combination with 68 Ga as a radionuclide, allows for a simple radiolabeling procedure which is preferable in a clinical setting using PET/CT. Methods: The peptides fragments UBI29-41, UBI30-41 were synthesized by standard microwave Fmoc/tert-butyl (tBu)-solid phase synthetic protocols. Characterizations were performed using analytical HPLC and LC/MS. Both NOTA-conjugated peptides were exposed to nat Ga 3+ ; their complexed form was quantified by direct LC/MS injection. This complexation was utilized to testify bacterial and mammalian cell binding potential of fluorophore-linked NOTA-UBI29-41/30-41. 68 Ga labeled NOTA-UBI fragments were also tested for competitive interaction to Staphylococcus aureus to proof the binding target. 68 Ga was eluted from SnO 2 - and TiO 2 -based 68 Ge/ 68 Ga generators using fractionated elution and anion exchanged-based post-procession. NOTA-peptide radiolabeling was carried out including optimization of buffer molarity, NOTA-peptide concentration(s), incubation temperature and –duration as well as considering various SPE purification cartridges. Results: Pure UBI29-41, UBI30-41 and NOTA-UBI30-41 were successfully characterized. Both, NOTA-UBI fragments exhibited complexation rates to nat Ga 3+ ≥ 99%. The percentage binding was significantly higher to Staphylococcus aureus bacilli over Mt4 human leucocytes (P > 0.05) for NOTA-UBI29-41[Lys(Abz)] < NOTA

Synthesis of two new alkyne-bearing linkers used for the preparation of siRNA for labeling by click chemistry with fluorine-18

International Nuclear Information System (INIS)

Flagothier, Jessica; Kaisin, Geoffroy; Mercier, Frederic; Thonon, David; Teller, Nathalie; Wouters, Johan; Luxen, André

2012-01-01

Oligonucleotides (ONs) and more particularly siRNAs are promising drugs but their pharmacokinetics and biodistribution are widely unknown. Positron Emission Tomography (PET) using fluorine-18 is a suitable technique to quantify these biological processes. Click chemistry (Huisgen cycloaddition) is the current method for labeling siRNA. In order to study the influence of a linker bearing by [ 18 F] labeled ONs, on the in vivo pharmacokinetic and metabolism, we have developed two modified ONs by two new linkers. Here we report the synthesis of two alkyne-bearing linkers, the incorporation onto a ONs and the conjugation by click chemistry with a [ 18 F] prosthetic group. - Highlights: ► Synthesis of two new alkyne linkers. ► Functionalization at the 3′-end siRNA by alkyne linker derived of proline. ► Click chemistry between alkyne modified siRNA and [ 18 F] prosthetic group.

Synthesis and radiolabelling of AG957 a potential tyrphostin PET radiotracer

International Nuclear Information System (INIS)

Ackermann, U.; Tochon-Danguy, H.J.; Sachinidis, J.; Burgess, A.W.; Scott, A.M.

2000-01-01

Full text: Signalling of tyrosine kinases is a critical component of intracellular regulation of growth and function. AG957 is an inhibitor of the c-ABL tyrosine kinase found in chronic myeloid leukemia, and the labelling of AG957 with a PET radiotracer would allow for the in vivo mapping of this receptor-kinase. Synthesis of the normethyl precursor of the tyrosine kinase inhibitor AG957 has been achieved by condensation of p-amino benzoic acid with 2,6 dihydroxy benzaldehyde and subsequent reduction of the imino function with sodium cyanoborohydride. The radiolabeling of this precursor using 11 C-methyliodide in basic conditions gave unsatisfactory yields because of decomposition of the starting material. We have therefore investigated the formation of 11 C-methyl esters using 11 Cmethanol and free carboxylic acids in the presence of either trimethylsilylchloride or boron trifluoride etherate as catalyst. P-amino benzoic acid, benzoic acid and salicylic acid were used as model compounds. Boron trifluoride etherate proved to be superior to trimethylsilylchloride giving good yields of the esters of the respective carboxylic acids when reacted with 11 C-methanol at 150 deg C. However, when this method was applied to desmethyl AG957, none of the desired product was obtained due to decomposition of the precursor at high temperatures. In light of these results we are planning to investigate the irreversible transesterification of enol esters with 11 C-methanol in the presence of a tin catalyst. This reaction is known to proceed smoothly at lower temperatures and should enable us to radiolabel the tyrosine kinase inhibitor 11 C-AG957. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

Comparison of 18F-FET and 18F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma

International Nuclear Information System (INIS)

Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Perryman, Lara; Erler, Janine; Poulsen, Hans Skovgaard; Stockhausen, Marie-Thérése; Lassen, Ulrik; Kjaer, Andreas

2016-01-01

Background: The radiolabeled amino acid O-(2- 18 F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3′-deoxy-3′- 18 F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts. Methods: Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUV max ) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated. Results: In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time. Conclusion: FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

Energy Technology Data Exchange (ETDEWEB)

Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

2013-10-15

The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

[18 F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18 F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors

International Nuclear Information System (INIS)

Mirfeizi, Leila; Rybczynska, Anna A.; Waarde, Aren van; Campbell-Verduyn, Lachlan; Feringa, Ben L.; Dierckx, Rudi A.J.O.; Elsinga, Philip H.

2014-01-01

Cerebral β‐adrenergic receptors (β‐ARs) play important roles in normal brain and changes of β-AR expression are associated with several neuropsychiatric illnesses. Given the high density of β‐AR in several brain regions, quantification of β‐AR levels using PET is feasible. However, there is a lack of radiotracers with suitable biological properties and meeting safety requirements for use in humans. We developed a PET tracer for β‐AR by 18 F‐fluorination of 1-((9H-carbazol-4-yl)oxy)-3-4(4-((2-(2-(fluoromethoxy)-ethoxy) methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ( 18 F-FPTC). Methods: [ 18 F] FPTC was synthesized by Cu(I)-catalyzed alkyne-azide cycloaddition. First, 18 F‐PEGylated alkyne was prepared by 18 F‐fluorination of the corresponding tosylate. Next 18 F‐PEGylated alkyne was reacted with an azidoalcohol derivative of 4‐hydroxycarbazol in the presence of the phosphoramidite Monophos as a ligand and Cu(I) as a catalyst. After purification with radio‐HPLC, the binding properties of [ 18 F FPTC were tested in β‐AR‐expressing C6‐glioma cells in vitro and in Wistar rats in vivo using microPET. Results: The radiochemical yield of 18 F‐PEGylated alkyne was 74%–89%. The click reaction to prepare [ 18 F]FPTC proceeded in 10 min with a conversion efficiency of 96%. The total synthesis time was 55 min from the end of bombardment. Specific activities were > 120 GBq/μmol. Propranolol strongly and dose-dependently inhibited the binding of both [ 125 I]-ICYP and [ 18 F]FPTC to C6 glioma cells, with IC 50 values in the 50–60 nM range. However, although both FPTC and propranolol inhibited cellular [ 125 I]ICYP binding, FPTC decreased [ 125 I]ICYP uptake by only 25%, whereas propranolol reduced it by 83%. [ 18 F]FPTC has the appropriate lipophilicity to penetrate the blood brain barrier (logP + 2.48). The brain uptake reached a maximum within 2 min after injection of 20–25 MBq [ 18 F]FPTC. SUV values ranged from 0.4 to 0.6 and were not

5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET.

Science.gov (United States)

Krämer, Stefanie D; Mu, Linjing; Müller, Adrienne; Keller, Claudia; Kuznetsova, Olga F; Schweinsberg, Christian; Franck, Dominic; Müller, Cristina; Ross, Tobias L; Schibli, Roger; Ametamey, Simon M

2012-03-01

Large neutral l-amino acids are substrates of system L amino acid transporters. The level of one of these, LAT1, is increased in many tumors. Aromatic l-amino acids may also be substrates of aromatic l-amino acid decarboxylase (AADC), the level of which is enhanced in endocrine tumors. Increased amino acid uptake and subsequent decarboxylation result in the intracellular accumulation of the amino acid and its decarboxylation product. (18)F- and (11)C-labeled neutral aromatic amino acids, such as l-3,4-dihydroxy-6-(18)F-fluorophenylalanine ((18)F-FDOPA) and 5-hydroxy-l-[β-(11)C]tryptophan, are thus successfully used in PET to image endocrine tumors. However, 5-hydroxy-l-[β-(11)C]tryptophan has a relatively short physical half-life (20 min). In this work, we evaluated the in vitro and in vivo characteristics of the (18)F-labeled tryptophan analog 5-(2-(18)F-fluoroethoxy)-l-tryptophan ((18)F-l-FEHTP) as a PET probe for tumor imaging. (18)F-l-FEHTP was synthesized by no-carrier-added (18)F fluorination of 5-hydroxy-l-tryptophan. In vitro cell uptake and efflux of (18)F-l-FEHTP and (18)F-FDOPA were studied with NCI-H69 endocrine small cell lung cancer cells, PC-3 pseudoendocrine prostate cancer cells, and MDA-MB-231 exocrine breast cancer cells. Small-animal PET was performed with the respective xenograft-bearing mice. Tissues were analyzed for potential metabolites. (18)F-l-FEHTP specific activity and radiochemical purity were 50-150 GBq/μmol and greater than 95%, respectively. In vitro cell uptake of (18)F-l-FEHTP was between 48% and 113% of added radioactivity per milligram of protein within 60 min at 37°C and was blocked by greater than 95% in all tested cell lines by the LAT1/2 inhibitor 2-amino-2-norboranecarboxylic acid. (18)F-FDOPA uptake ranged from 26% to 53%/mg. PET studies revealed similar xenograft-to-reference tissue ratios for (18)F-l-FEHTP and (18)F-FDOPA at 30-45 min after injection. In contrast to the (18)F-FDOPA PET results, pretreatment with the

Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology

DEFF Research Database (Denmark)

Stauss, J.; Franzius, C.; Pfluger, T.

2008-01-01

tomography ((18)F-FDG PET) in paediatric oncology. The Oncology Committee of the European Association of Nuclear Medicine (EANM) has published excellent procedure guidelines on tumour imaging with (18)F-FDG PET (Bombardieri et al., Eur J Nucl Med Mol Imaging 30:BP115-24, 2003). These guidelines, published...

Synthesis and Biological Evaluation of a New Acyclic Pyrimidine Derivative as a Probe for Imaging Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression

Directory of Open Access Journals (Sweden)

Simon M. Ametamey

2013-07-01

Full Text Available With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk gene expression by means of positron emission tomography (PET, a novel [18F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethylbutyl side chain at N-1 (HHB-5-[18F]FEP was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[18F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [18F]fluoride-cryptate complex in 45% ± 4 (n = 4 radiochemical yields and high purity (>99%. The biological evaluation indicated the feasibility of using HHB-5-[18F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.

F-18-FDG PET of the thyroid in Graves` disease; F-18-FDG-PET der Schilddruese bei Morbus Basedow

Energy Technology Data Exchange (ETDEWEB)

Boerner, A.R.; Voth, E.; Schicha, H. [Klinik und Poliklinik fuer Nuklearmedizin, Koeln Univ. (Germany); Wienhard, K.; Wagner, R. [Max-Planck-Institut fuer Neurologische Forschung, Koeln (Germany)

1998-12-31

This study evaluates F-18-FDG PET of the thyroid in Graves` disease. Methods: Thirty patients were investigated the day before radioiodine therapy, 15 patients 3-10 days after radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. Results: F-18-FDG uptake was higher in Graves` disease patients than in controls. Negative correlations of F-18-FDG uptake with half-life of radioiodine and absorbed radiation dose due to radioiodine therapy were found along with a positive correlation to autoantibody levels. Conclusion: Thus F-18-FDG PET is likely to give information on the biological activity of Graves` disease as well as on early radiation effects. (orig.) [Deutsch] Ziel: Diese Studie evaluiert F-18-Fluoro-Deoxy-Glukose (F-18-FDG) PET der Schilddruese bei Patienten mit M. Basedow. Methoden: 30 Patienten wurden am Tag vor Radioiod-Therapie, 15 Patienten am 3.-10. Tag nach Radioiodtherapie untersucht. 20 Patienten mit Kopf/Halstumoren und normaler Schilddruesenfunktion dienten als Kontrollgruppe. Ergebnisse: Die F-18-FDG-Aufnahme in der Schilddruese war signifikant hoeher bei Patienten mit M-Basedow im Vergleich zu den Kontrollen. Sie stieg mit hoeheren, antithyreoidalen Antikoerpern und sank bei laengerer I-131-Halbwertzeit. Es bestand eine Korrelation einer reduzierten Glukose-Utilisation bei hoeherer absorbierter Schilddruesendosis nach Radioiod-Therapie. Schlussfolgerung: Damit erscheint die F-18-FDG-PET-Untersuchung zur biologischen Aktivitaetsbeurteilung des M. Basedow und Darstellung von fruehen Strahleneffekten geeignet. (orig.)

Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

NARCIS (Netherlands)

Doze, P; Elsinga, PH; de Vries, EFJ; Van Waarde, A; Vaalburg, W

S-1'[F-18]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). Tn former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in

{sup 18}F-FDOPA PET/CT imaging of insulinoma revisited

Energy Technology Data Exchange (ETDEWEB)

Imperiale, Alessio; Namer, Izzie-Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); University of Strasbourg/CNRS and FMTS, Faculty of Medicine, ICube - UMR 7357, Strasbourg (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, La Timone University Hospital, Marseille (France); Vix, Michel [University of Strasbourg, Department of General, Digestive, and Endocrine Surgery, IRCAD-IHU, Strasbourg (France); Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Diabetes and Metabolic Disorders, La Timone University Hospital, Marseille (France); Kessler, Laurence; Moreau, Francois [University of Strasbourg, Department of Diabetology, University Hospital of Strasbourg, Strasbourg (France); Bachellier, Philippe [University Hospitals of Strasbourg, Department of Visceral Surgery and Transplantation, Strasbourg (France); Guillet, Benjamin; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Aix-Marseille University, Biophysics and Nuclear Medecine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France)

2014-11-01

{sup 18}F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to {sup 18}F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with {sup 18}F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using {sup 18}F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after {sup 18}F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after {sup 18}F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, {sup 18}F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All {sup 18}F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted {sup 18}F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without

18FDG-labeled LIKKPF. A PET tracer for apoptosis imaging

International Nuclear Information System (INIS)

Sepideh Khoshbakht; Davood Beiki; Parham Geramifar; Farzad Kobarfard; Omid Sabzevari; Mohsen Amini; Soraya Shahhosseini

2016-01-01

One of the early biochemical changes of apoptotic cells is exposure of phosphatidylserine on the external surface of the plasma membrane. The aim of current study is targeting Phosphatidyl serine (PS) using radiolabeled LIKKPF, which was functionalized with HYNIC and aminooxy, radiolabeled with 18 FDG and assessed in vitro and in vivo. Results showed LIKKPF has less affinity to PS compared to original phage peptide, but high enough for specific binding to apoptotic cells. It is concluded the low affinity of radiolabeled LIKKPF might be attributed to hydrophobicity of peptide, therefor peptides used in future studies should be more hydrophobic compared to LIKKPF. (author)

Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results.

Science.gov (United States)

Ghai, Aanchal; Singh, Baljinder; Panwar Hazari, Puja; Schultz, Michael K; Parmar, Ambika; Kumar, Pardeep; Sharma, Sarika; Dhawan, Devinder; Kumar Mishra, Anil

2015-11-01

The present study describes the optimization of (68)Ga radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([(68)Ga]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the (68)Ga labeled product for imaging and treating angiogenesis respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Unusual Case of Plasmablastic Lymphoma Presenting as Paravertebral Mass Evaluated by {sup 18}F-FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio; Paone, Gaetano; Stathis, Anastasios; Ceriani, Luca; Giovanella, Luca [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

2014-03-15

A 60-year-old man underwent radiological investigations due to the onset of back pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed the presence of a paravertebral mass located ahead the body of the third thoracic vertebra. Based on these findings the patient underwent biopsy of the paravertebral mass, which showed the presence of a plasmablastic lymphoma. Therefore, the patient underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) for staging. Before {sup 18}F-FDG injection, the patient had fasted for at least 6 h; at the time of the radiopharmaceutical injection he presented glucose blood levels corresponding to 98 mg/dl. Images were acquired 1 h after intravenous injection of 280 MBq of {sup 18}F-FDG according to the body mass index. PET images were interpreted visually and semiquantitatively by using the maximal standardized uptake value (SUVmax). {sup 18}F-FDG PET/CT showed moderate radiopharmaceutical uptake corresponding to the paravertebral lesion (SUVmax 3.3) and diffuse uptake in the skeleton suspicious for bone marrow neoplastic involvement, with more evident hypermetabolic areas in the left scapula (SUVmax 3.7), right sixth rib (SUVmax 3.5), and left iliac bone (SUVmax 3.4) (Fig. 1). Subsequent bone marrow biopsy confirmed the bone marrow infiltration by plasmablastic cells. Based on these findings, a final diagnosis of plasmablastic lymphoma with bone marrow involvement was performed and the patient was addressed to chemotherapy. Plasmablastic lymphoma is a rare CD20-negative large-cell lymphoma with plasmablastic features occurring primarily in HIV or Epstein-Barr virus positive individuals. Distinguishing this tumor from myeloma could be challenging. The most frequent site of presentation is the oral cavity, whereas extraoral localizations of plasmablastic lymphoma are considered to be very rare and they should be differentiated from extraosseous localization of

Oncological applications of 18F-FDG PET imaging

International Nuclear Information System (INIS)

Li Lin

2000-01-01

Considering normal distribution of 18 F-FDG in human body, 18 F-FDG imaging using PET can be applied to brain tumors, colorectal cancer, lymphoma, melanoma, lung cancer and head and neck cancer. The author briefly focuses on application of 18 F-FDG PET imaging to breast cancer, pancreatic cancer, hepatocellular carcinoma, musculoskeletal neoplasms, endocrine neoplasms, genitourinary neoplasms, esophageal and gastric carcinomas

68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

Science.gov (United States)

Young, Jennifer D; Abbate, Vincenzo; Imberti, Cinzia; Meszaros, Levente K; Ma, Michelle T; Terry, Samantha Y A; Hider, Robert C; Mullen, Greg E; Blower, Philip J

2017-08-01

The clinical impact and accessibility of 68 Ga tracers for the prostate-specific membrane antigen (PSMA) and other targets would be greatly enhanced by the availability of a simple, 1-step kit-based labeling process. Radiopharmacy staff are accustomed to such procedures in the daily preparation of 99m Tc radiopharmaceuticals. Currently, chelating agents used in 68 Ga radiopharmaceuticals do not meet this ideal. The aim of this study was to develop and evaluate preclinically a 68 Ga radiotracer for imaging PSMA expression that could be radiolabeled simply by addition of 68 Ga generator eluate to a cold kit. Methods: A conjugate of a tris(hydroxypyridinone) (THP) chelator with the established urea-based PSMA inhibitor was synthesized and radiolabeled with 68 Ga by adding generator eluate directly to a vial containing the cold precursors THP-PSMA and sodium bicarbonate, with no further manipulation. It was analyzed after 5 min by instant thin-layer chromatography and high-performance liquid chromatography. The product was subjected to in vitro studies to determine PSMA affinity using PSMA-expressing DU145-PSMA cells, with their nonexpressing analog DU145 as a control. In vivo PET imaging and ex vivo biodistribution studies were performed in mice bearing xenografts of the same cell lines, comparing 68 Ga-THP-PSMA with 68 Ga-HBED-CC-PSMA. Results: Radiolabeling was complete (>95%) within 5 min at room temperature, showing a single radioactive species by high-performance liquid chromatography that was stable in human serum for more than 6 h and showed specific binding to PSMA-expressing cells (concentration giving 50% inhibition of 361 ± 60 nM). In vivo PET imaging showed specific uptake in PSMA-expressing tumors, reaching 5.6 ± 1.2 percentage injected dose per cubic centimeter at 40-60 min and rapid clearance from blood to kidney and bladder. The tumor uptake, biodistribution, and pharmacokinetics were not significantly different from those of 68 Ga

One-step radiosynthesis of {sup 18}F-AlF-NOTA-RGD{sub 2} for tumor angiogenesis PET imaging

Energy Technology Data Exchange (ETDEWEB)

Liu, Shuanglong; Liu, Hongguang; Xu, Yingding; Cheng, Zhen [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Jiang, Han [Stanford University, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford, CA (United States); Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China); Zhang, Hong [Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Department of Nuclear Medicine, Medical PET Center, Hangzhou, Zhejiang (China)

2011-09-15

One of the major obstacles of the clinical translation of {sup 18}F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al{sup 18}F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step {sup 18}F labeling strategy for development of a PET probe for tumor angiogenesis imaging. Dimeric cyclic peptide E[c(RGDyK)]{sub 2} (RGD{sub 2}) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD{sub 2} was then radiofluorinated via Al{sup 18}F intermediate to synthesize {sup 18}F-AlF-NOTA-RGD{sub 2}. Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using {sup 125}I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of {sup 18}F-AlF-NOTA-RGD{sub 2} were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution. NOTA-RGD{sub 2} was successfully {sup 18}F-fluorinated with good yield within 40 min using the Al{sup 18}F intermediate. The IC{sub 50} of {sup 19}F-AlF-NOTA-RGD{sub 2} was determined to be 46 {+-} 4.4 nM. Quantitative microPET studies demonstrated that {sup 18}F-AlF-NOTA-RGD{sub 2} showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios. NOTA-RGD{sub 2} bioconjugate has been successfully prepared and labeled with Al{sup 18}F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of {sup 18}F-AlF-NOTA-RGD{sub 2} warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of {sup 18}F-labeled RGD peptides. (orig.)

Positron emission tomography (PET) for oncologic applications in oral region

International Nuclear Information System (INIS)

Shozushima, Masanori; Terasaki, Kazunori

2004-01-01

A rapidly emerging clinical application of positron emission tomography (PET) is the detection of cancer with radionuclide tracer, because it provides information unavailable by ultrasound, computed tomography or magnetic resonance imaging. The most commonly used radiotracer for PET oncologic imaging is fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG). Early studies show PET has potential value in viewing the region of the tumor, detecting, staging, grading, monitoring response to anticancer therapy, and differentiating recurrent or residual disease from post treatment changes. However, limitations of FDG-PET in the head and neck region, namely, physiological FDG uptake in the salivary glands and palatine tonsils, have been reported, increasing the false-positive rates in image interpretation. This review was designed to address these distinctions of oral cancer PET imaging: specialization of PET equipment, cancer cell metabolism, proliferation and tracers, clinical diagnosis of oral cancer with PET, pitfalls in oncologic diagnosis with FDG-PET imaging. (author)

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

Science.gov (United States)

Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

2017-01-01

The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

Comparison of 18F-FDG PET/CT and PET/MRI in patients with multiple myeloma

OpenAIRE

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Mosebach, Jennifer; Pan, Leyun; Schlemmer, Heinz-Peter; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

PET/MRI represents a promising hybrid imaging modality with several potential clinical applications. Although PET/MRI seems highly attractive in the diagnostic approach of multiple myeloma (MM), its role has not yet been evaluated. The aims of this prospective study are to evaluate the feasibility of 18F-FDG PET/MRI in detection of MM lesions, and to investigate the reproducibility of bone marrow lesions detection and quantitative data of 18F-FDG uptake between the functional (PET) component ...

Comparison of 18F-FET PET and perfusion-weighted MRI for glioma grading. A hybrid PET/MR study

International Nuclear Information System (INIS)

Verger, Antoine; Filss, Christian P.; Lohmann, Philipp; Stoffels, Gabriele; Rota Kops, Elena; Sabel, Michael; Wittsack, Hans J.; Galldiks, Norbert; Fink, Gereon R.; Shah, Nadim J.; Langen, Karl-Josef

2017-01-01

Both perfusion-weighted MR imaging (PWI) and O-(2- 18 F-fluoroethyl)-L-tyrosine PET ( 18 F-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of 18 F-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner. Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with 18 F-FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBR mean , TBR max ) were calculated. In addition, Time-to-Peak (TTP) and slopes of time-activity curves were calculated for 18 F-FET PET. Diagnostic accuracies of 18 F-FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC). The diagnostic accuracy of 18 F-FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBR mean and TBR max of 18 F-FET PET uptake (0.80, 0.83) and for TBR mean and TBR max of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 ± 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy. Both 18 F-FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by 18 F-FET PET and PWI is based on different pathophysiological phenomena. (orig.)

Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

Directory of Open Access Journals (Sweden)

Teik Hin Tan

2016-07-01

Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose

International Nuclear Information System (INIS)

Schreckenberger, M.; Sabri, O.; Arning, C.; Schulz, G.; Tuttass, T.; Wagenknecht, G.; Kaiser, H.J.; Buell, U.; Gouzoulis-Mayfrank, E.; Sass, H.

1998-01-01

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling

Synthesis of [{sup 18}F]-labelled nebivolol as a β{sub 1}-adrenergic receptor antagonist for PET imaging agent

Energy Technology Data Exchange (ETDEWEB)

Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup (Korea, Republic of); Chang, Dong Jo [College of pharmacy, Sunchon National University, Suncheon (Korea, Republic of)

2017-02-15

Selective β{sub 1}-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β{sub 1}-antagonists including nebivolol have high binding affinity on β{sub 1}-adrenergic receptor, not β{sub 2}-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β{sub 1}-blockers in clinically used β{sub 1}- blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β{sub 1}-blocker. Nebivolol is C{sub 2}-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of {sup 18}F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for {sup 18}F-aromatic substitution, was synthesized in moderate yield which was readily subjected to {sup 18}F-aromatic substitution to give {sup 18}F-labelled nebivolol.

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors

Energy Technology Data Exchange (ETDEWEB)

Iwata, Yoshinori; Shiomi, Susumu; Sasaki, Nobumitsu; Jomura, Hisato; Nishiguchi, Shuhei; Seki, Shuichi; Kawabe, Joji; Ochi, Hironobu [Osaka City Univ. (Japan). Medical School

2000-04-01

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the {alpha}-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC. (author)

Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography

International Nuclear Information System (INIS)

Dolle, F.; Luus, C.; Reynolds, A.; Kassiou, M.

2009-01-01

The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuro inflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of micro-glial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed high affinity, selective TSPO ligands in conjunction with functional imaging modalities such as positron emission tomography (PET), it becomes possible to study the process of micro-glial activation in the living brain. A number of high affinity ligands, the majority of which are C, N-substituted acetamide derivatives, have been successfully radiolabelled and used in in vivo studies of the TSPO and the process of micro-glial activation. This review highlights recent achievements (up to December 2008) in the field of functional imaging of the TSPO as well as the radio-syntheses involved in such studies. (authors)

Role of 18F-FDG PET/CT in diagnosing peritoneal carcinomatosis in the restaging of patient with ovarian cancer as compared to contrast enhanced CT and tumor marker Ca-125.

Science.gov (United States)

Rubini, G; Altini, C; Notaristefano, A; Merenda, N; Rubini, D; Ianora, A A Stabile; Asabella, A Niccoli

2014-01-01

To investigate the role of whole-body fluorine-18-2-deoxy-2-fluoro-d-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the identification of peritoneal carcinomatosis in patients with ovarian cancer (OC). Seventy-nine patients with histologically proven stages III-IV OC who underwent (18)F-FDG PET/CT were studied retrospectively. We considered group A as 51 patients who also underwent computed-tomography with contrast-enhancement (CECT), and group B as 35 patients who had also been tested for biomarker Ca-125. Sensitivity, specificity, accuracy, positive predictive values (PPV) and negative predictive values (NPV) of (18)F-FDG PET/CT as compared to CECT and to Ca-125 were evaluated. (18)F-FDG PET/CT' sensitivity, specificity, accuracy, PPV and NPV for all 79 patients were: 85%, 92.31%, 88.61%, 91.89% and 85.71%, respectively. (18)F-FDG PET/CT sensitivity in group A was 78.6%, while it was 53.6% for CECT. (18)F-FDG PET/CT specificity, calculated in the same group, was 91.3%, while that of CECT was 60.9% (statistically significant difference, McNemar 4, P=0.039). Accuracy was 84.3% and 56.9%, respectively. (18)F-FDG PET/CT' sensitivity in group B was 86.4%, while that of Ca-125 was 81.8% (no statistical difference, McNemar 0, P=1). (18)F-FDG PET/CT specificity in group B was 84.6% while that of Ca-125 was 38.5% (clear but not statistically significant difference, McNemar 3.12, P=0.070). Accuracy calculated in the same group was 85.7% for (18)F-FDG PET/CT and 65.7% for Ca-125. (18)F-FDG PET/CT is a useful diagnostic tool when peritoneal biopsy cannot be performed and it can better select those who are candidates for adjuvant chemotherapy. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.