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At least 19 recordsLinked to original sources
PubMed1981

Tissue distribution studies of [18F]haloperidol, [18F]-beta-(4-fluorobenzoyl)propionic acid, and [82Br]bromperidol by external scintigraphy.

Tissue distribution studies of [18F]haloperidol and [82Br]bromperidol, two potent neuroleptic drugs, were performed in rats by serial sacrifice. The usefulness of external scintigraphy in obtaining tissue distribution data in large animals is demonstrated by the tissue distribution of [18F]haloperidol in rhesus monkeys. Both serial sacrifice and external scintigraphic studies demonstrated that uptake of the two drugs after intravenous administration into their target organ, the brain, was very fast and that the ratio of brain to blood levels was high throughout the 2-hr observation. Bromperidol appeared to reach peak brain levels faster than its chloro analog, haloperidol. Both bromperidol and haloperidol concentrated overwhelmingly in the rat lung. Haloperidol also showed a high affinity for the monkey lung. The disposition pattern in rats of [18F]-beta-(4-fluorobenzoyl)propionic acid, an apparent intermediate in butyrophenone metabolism, was entirely different from that of the parent drugs. This metabolite did not concentrate in the rat brain.

Animals↗
PubMed2005

Binding characteristics of the 5-HT2A receptor antagonists altanserin and MDL 100907.

To study the 5-HT(2A) receptors in the living human brain, using positron emission tomography (PET), two selective radiotracers are currently in use: [(18)F]altanserin and [(11)C]MDL 100907. It is, however, currently unknown to what extent data obtained with either tracer are directly comparable. The aim of this study was to compare binding characteristics of these two radiotracers in rat brain with respect to affinity (K(d)), receptor binding density (B(max)), binding potential (BP), and nonspecific binding. Further, binding kinetics, sensitivity towards competition with the endogenous transmitter serotonin, and the competitive/noncompetitive interaction between the two radioligands were evaluated. In addition, the selectivity of [(18)F]altanserin for the 5-HT(2A) receptor was assessed. The K(d) value of [(18)F]altanserin and [(3)H]MDL 100907 was in the order of 0.3 nM. B(max) in frontal cortex was 523 and 527 fmol/mg protein, respectively. The binding of [(18)F]altanserin was not influenced by blocking either the 5-HT(2B/2C) or the alpha(1)-adrenergic receptors. At 37 degrees C the association t(1/2) was 2.8 and 2.7 min and the dissociation t(1/2) was 11 and 13.5 min for [(18)F]altanserin and [(3)H]MDL 100907, respectively. Both radioligands were displaced by 5-HT, only at high concentrations; the K(i) value of 5-HT ranging between 650 and 3,300 nM. This indicates that binding of both radioligands in PET studies is not directly influenced by changes in endogenous 5-HT.Overall, the binding of [(18)F]altanserin and [(3)H]MDL 100907 to the 5-HT(2A) receptor was very comparable, showing selective high affinity binding in the subnanomolar range.

Animals↗
PubMed1992

Amino acids for the measurement of protein synthesis in vivo by PET.

In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1-11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2-18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose.

Amino Acids↗
PubMed1995

Design of gas targets for the production of medically used radionuclides with the help of Monte-Carlo simulation of small angle multiple scattering of charged particles.

Due to scattering of protons or deuterons in the target gas the radius of beams increases with increasing penetration depth of the particles. The increase depends on the kind of beam particle, the energy, the target gas and its temperature and pressure. A Monte-Carlo program was developed for stimulation of multiple scattering. The initial beam has a particle distribution of variable sinusoidal shape behind the entrance window and may be cut off by the simulation of a collimator. The beam distribution is calculated for up to 14 planes representing energy values of the particles due to a predefined range from one plane to the next. The energy loss is calculated with the help of an integrated Bethe-Bloch routine. The distribution of the particles within the plane may be rearranged into profiles and transferred to a spreadsheet for further manipulation and graphical printout. Simulations are carried out for radionuclide production routes, commonly used for position emission tomography (PET).

Carbon Radioisotopes↗
PubMed1996

Positron-labeled antioxidant 6-deoxy-6-[18F]fluoro-L-ascorbic acid: increased uptake in transient global ischemic rat brain.

The in vivo uptake and distribution of 6-deoxy-6-[18F]fluoro-L-ascorbic acid (18F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time points were chosen for 18F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of 18F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of 18F-DFA, compared to the sham-operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in vivo accumulation of 45Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using 19F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that 18F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.

Animals↗
PubMed2005

Modeling and analysis of PET studies with norepinephrine transporter ligands: the search for a reference region.

UNLABELLED: The development of positron emission tomography (PET) ligands for the norepinephrine transporter (NET) has been slow compared to the development of radiotracers for others systems, such as the dopamine (DAT) or the serotonin transporters (SERT). The main reason for this appears to be the high nonspecific (non-NET) binding exhibited by many of these tracers, which makes the identification of a reference region difficult. With other PET ligands the use of a reference region increases the reproducibility of the outcome measure in test/retest studies. The focus of this work is to identify a suitable reference region or means of normalizing data for the NET ligands investigated. METHODS: We have analyzed the results of PET studies in the baboon brain with labeled reboxetine derivatives (S,S)-[(11)C]O-methyl reboxetine (SS-MRB), (S,S)-[(18)F]fluororeboxetine (SS-FRB) as well as O-[(11)C]nisoxetine and N-[(11)C]nisoxetine (NIS), and, for comparison, the less active (R,R) enantiomers (RR-MRB, RR-FRB) in terms of the distribution volume (DV) using measured arterial input functions. RESULTS: (1) For a given subject, a large variation in DV for successive baseline studies was observed in regions with both high and low NET density. (2) The occipital cortex and the basal ganglia were found to be the regions with the smallest change between baseline (SS-MRB) and pretreatment with cocaine, and were therefore used as a composite reference region for calculation of a distribution volume ratio (DVR). (3) The variability [as measured by the coefficient of variation (CV) = standard deviation/mean] in the distribution volume ratio (DVR) of thalamus (to reference region) was considerably reduced over that of the DV using this composite reference region. (4) Pretreatment with nisoxetine (1.0 mg/kg 10 min prior to tracer) in one study produced (in decreasing order) reductions in thalamus, cerebellum, cingulate and frontal cortex consistent with known NET densities. (5) [(11)C]Nisoxetine had a higher background non-NET binding (DV) than the other tracers reported here with basal ganglia (a non-NET region) higher than thalamus. CONCLUSIONS: The reboxetine derivatives show a lot of promise as tracers for human PET studies of the norepinephrine system. We have identified a strategy for normalizing DVs to a reference region with the understanding that the DVR for these tracers may not be related to the binding potential in the same way as, for example, for the dopamine tracers, since the non-NET binding may differ between the target and nontarget regions. From our baboon studies the average DVR for thalamus (n = 18) for SS-MRB is 1.8; however, the lower limit is most likely less than 1 due to this difference in non-NET binding.

Animals↗
PubMed2004

Update on PET radiopharmaceuticals: life beyond fluorodeoxyglucose.

Twenty-eight years after its inception, 2-[18F]FDG- is still the most widely used radiopharmaceutical for PET studies, but numerous more specific radiotracers have been developed and applied in neuroscience and oncology. The advances in radiotracer chemistry, especially the nucleophilic substitution reaction, have played the pivotal role in synthesizing various no-carrier-added 18F-labeled radiotracers for PET studies of various receptor systems. This article lists some of the radiotracers that are available for PET studies in neuroscience and oncology. The prospects for developing other new radiotracers for imaging other organ diseases also seem to be promising.

Brain↗
PubMed2003

N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A): A PET tracer for imaging brain acetylcholinesterase in vivo.

N-[(18)F]Fluoroethyl-4-piperidyl acetate ([(18)F]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [(18)F]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[(18)F]fluoroethyl bromide ([(18)F]FEtBr) at 130 degrees C for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [(18)F]FEtP4A was synthesized by reacting P4A with 2-[(18)F]fluoroethyl iodide ([(18)F]FEtI) or 2-[(18)F]fluoroethyl triflate ([(18)F]FEtOTf in improved radiochemical yields, compared with [(18)F]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [(18)F]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of (18)F radioactivity was consistent with that of AchE in the brain: striatum>frontal cortex>cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [(18)F]fluoroethyl-4-piperidinol ([(18)F]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [(18)F]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [(18)F]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [(11)C]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain.

Acetates↗
PubMed2000

Generic models for radionuclide dosimetry: 11C-, 18F- or 75Se-labelled amino acids.

A generic biokinetic model was developed for use in the assessment of the internal dose received by human subjects injected with amino acids labelled with 11C (T1/2 = 0.34 h, beta+, gamma), 18F(T1/2 = 1.83 h, beta+, gamma) or 75Se (T1/2 = 119.8 d, beta-, gamma). This generic model was used in conjunction with the MIRDOSE 3 computer programme to calculate radiation doses to adults; these radiation doses were compared with those calculated using compound-specific models for two [11C]-, and eight [18F]-labelled amino acids and [75Se]selenomethionine. In general, the effective doses, as well as the organ and tissue doses, calculated using the generic model agreed within a factor of 2 or less, with those calculated using compound-specific models; the generic model tended to over-, rather than underestimate the organ and tissue doses. It was concluded that for 11C- and 18F-labelled amino acids and for 75Se-labelled amino acids or their analogues, the single generic biokinetic model could be applied for general radiation protection purposes.

Adult↗
PubMed2001

Assessment of cardiac sympathetic nerve integrity with positron emission tomography.

The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation.

3-Iodobenzylguanidine↗
PubMed2001

Imaging hypoxia in tumors.

For many years, it has been known that hypoxia affects the response to radiotherapy in human cancers. Hypoxic regions can develop as a tumor grows beyond the ability of its blood supply to deliver oxygen to the full extent of the tumor, exacerbated by vascular spasm or compression caused by increased interstitial fluid pressure. However, hypoxia is heterogeneous, and tumors that appear identical by clinical and radiographic criteria can vary greatly in their extent of hypoxia. Several invasive procedures to measure hypoxia in tumors have been developed and are predictive of response to therapy, but none of these is in routine clinical use because of technical complexity, inconvenience, and inability to obtain repeated measures. Noninvasive imaging with a hypoxia-directed radiopharmaceutical could be of great clinical utility. Most such radiopharmaceuticals under development use 2-nitroimidazole as the targeting moiety. 2-Nitroimidazole, which is selectively reduced and bound in hypoxic tissues, has been labeled with F-18, Cu-64/67, I-123, and Tc-99m. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA) have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91), have also been evaluated. In particular, 1-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors.

Animals↗
PubMed2002

Quantitative imaging and correction for cascade gamma radiation of 76Br with 2D and 3D PET.

Several positron emitting nuclides with applications in PET, such as 76Br, 124I, 110In and 86Y, also emit gamma radiation in their decays. Measured coincidences between annihilation photons and this cascade gamma radiation are essentially true coincidences and the standard PET corrections do not account for them. We investigated the performance of 76Br in 2D and 3D PET, the effect of the gamma radiation emitted by 76Br on quantitative accuracy and the distribution of cascade gamma radiation coincidences in 2D and 3D PET sinograms. A correction method for cascade gamma radiation coincidences was implemented and evaluated. Count rate linearity was affected by the gamma radiation from the 76Br decay. Spatial resolution and sphere recovery were slightly worse for 76Br compared to 18F. Correction for cascade gamma radiation coincidences by subtraction of a linear projection tail fit improved total correction accuracy to similar values as for positron-only emitters such as 18F, and improved image contrast significantly.

Bromine Radioisotopes↗
PubMed2002

Molecular imaging of gliomas.

Gliomas are the most common types of brain tumors. Although sophisticated regimens of conventional therapies are being carried out to treat patients with gliomas, the disease invariably leads to death over months or years. Before new and potentially more effective treatment strategies, such as gene- and cell-based therapies, can be effectively implemented in the clinical application, certain prerequisites have to be established. First of all, the exact localization, extent, and metabolic activity of the glioma must be determined to identify the biologically active target tissue for a biological treatment regimen; this is usually performed by imaging the expression of up-regulated endogenous genes coding for glucose or amino acid transporters and cellular hexokinase and thymidine kinase genes, respectively. Second, neuronal function and functional changes within the surrounding brain tissue have to be assessed in order to save this tissue from therapy-induced damage. Third, pathognomonic genetic changes leading to disease have to be explored on the molecular level to serve as specific targets for patient-tailored therapies. Last, a concerted noninvasive analysis of both endogenous and exogenous gene expression in animal models as well as the clinical setting is desirable to effectively translate new treatment strategies from experimental into clinical application. All of these issues can be addressed by multi-modal radionuclide and magnetic resonance imaging techniques and fall into the exciting and fast growing field of molecular and functional imaging. Noninvasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging may reveal the assessment of the "location," "magnitude," and "duration" of therapeutic gene expression and its relation to the therapeutic effect. Detailed reviews on molecular imaging have been published from the perspective of radionuclide imaging (Gambhir et al., 2000; Blasberg and Tjuvajev, 2002) as well as magnetic resonance and optical imaging (Weissleder, 2002). The present review focuses on molecular imaging of gliomas with special reference on the status and perspectives of imaging of endogenous and exogenously introduced gene expression in order to develop improved diagnostics and more effective treatment strategies of gliomas and, in that, to eventually improve the grim prognosis of this devastating disease.

Animals↗
PubMed2002

[Implementation of a measurement protocol to evaluate system parameters in positron emission tomography].

To evaluate system parameters in PET measurements, several different activity ratios of the investigated phantom must be analyzed. The aim of this study was to develop a measurement protocol which requires just one filling of the phantom to measure adequate image contrasts and count ranges. We used 11C for the hollow spheres and 18F for the background of the whole-body PET phantom. Because of the different half-lives of the radionuclides, the dynamic acquisition of the frames (duration compensated for 18F decay) realizes various activity ratios between the spheres and the constant background. By summing up different frames, the counts in the background can also be varied. The presented method reduces the radiation exposure of the staff and economizes the use of the tomograph.

Carbon Radioisotopes↗
PubMed1992

Tumor radiotherapy monitoring with radioscintigraphy tracers: a comparative study with multiple-tracer technique.

A comparative multiple-tracer study was performed to assess the tracer feasibility of monitoring tumor radiotherapy. Metabolic tracers for glucose, amino acid, nucleic acid metabolism: F-18-FDG, C-14-Met, H-3-Thd, and F-18-FdUrd and conventional Ga-67 were compared in the same AH109A radiotherapy model using a new quadruple-tracer technique. F-18-FDG showed a large uptake change and a steady response to radiotherapy which is similar to Ga-67. F-18-FdUrd showed a rapid decrease, but the range of change in uptake was narrow. H-3-Thd and C-14-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that if labeled with C-11, they may be feasible for PET study.

Animals↗