Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain

The purpose of this study was to synthesize 6-[1-(2-[¹⁸F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline ([¹⁸F]FPTQ, [¹⁸F]7a) and to evaluate its potential as a positron emission tomography ligand for imaging metabotropic glutamate receptor type 1 (mGluR1) in the rat brain. Compound [¹⁸F]7a was synthesized by [¹⁸F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline (7b) with potassium [¹⁸F]fluoride. At the end of synthesis, 1280-1830 MBq (n = 8) of [¹⁸F]7a was obtained with >98% radiochemical purity and 118-237 GBq/??mol specific activity using 3300-4000 MBq of [¹⁸F]F⁻. In vitro autoradiography showed that [¹⁸F]7a had high specific binding with mGluR1 in the rat brain. Biodistribution study using a dissection method and small-animal PET showed that [¹⁸F]7a had high uptake in the rat brain. The uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1-selective ligand JNJ-16259685 (2), indicating that [¹⁸F]7a had in vivo specific binding with mGluR1. Because of a low amount of radiolabeled metabolite present in the brain, [¹⁸F]7a may have a limiting potential for the in vivo imaging of mGluR1 by PET.     

Direct labelling of peptides with 2-[F]fluoro-2-deoxy-d-glucose ([F]FDG)

The study describes the use of [¹⁸F]FDG as ¹⁸F building block for the direct labelling of various aminooxy-functionalised peptides via chemoselective oxime formation.     

A Kinetic Analysis of 6-[18F]Fluoro-l-Dihydroxyphenylalanine Metabolism in the Rat

Abstract: A previous study of the metabolism of 6-[¹⁸F]-fluoro-l -3,4-dihydroxyphenylalanine (FDOPA) in rats pretreated with carbidopa contained information amenable to kinetic analysis. Using these data, tracer transfer coefficients and metabolic rate constants were estimated. After intravenous injection, FDOPA in circulation was O-methylated (k^D₀ = 0.055 min^?1), and the metabolite (O-methyl-FDOPA) escaped from plasma with a rate constant (k^M_?1) of 0.01 min^?1. The initial clearance of FDOPA to striatum (K^D₁) was 0.07 ml g^?1 min^?1, and the equilibrium distribution volume (V^D_e) was 0.67 ml g^?1. The initial clearance of O-methyl-FDOPA to striatum (K^M₁) was 0.08 ml g^?1 min^?1, and the equilibrium distribution volume (V^M_e) was 0.75 ml g^?1. The rate constant of FDOPA decarboxylation (k^D₃) was 0.17 min^?1 in striatum. The elimination of 6-[¹⁸F]fluorodopamine (FDA) from striatum suggested an apparent rate constant for monoamine oxidase activity (k′₇) of 0.055 min^?1. 6-[¹⁸F]Fluorohomovanillic acid (FHVA) was formed from 6-[¹⁸F]fluoro-l -3,4-dihydroxyphenylacetic acid with a rate constant (k₁₁) of 0.083 min^?1, and FHVA was eliminated from striatum (k₉) with a rate constant of 0.12 min^?1. The steady-state concentration ratios of FDA and its metabolites were shown to be functions of these rate constants.     

The Metabolism of [18F]6-Fluoro-l-3,4-Dihydroxyphenylalanine in the Hooded Rat

The metabolism of the positron-emitting compound [18F]6-fluoro-L-3,4-dihydroxyphenylalanine (*F-DOPA) was studied in carbidopa-pretreated male hooded rats. Thirty minutes following carbidopa administration (5 mg/kg i.p.), animals received *F-DOPA (500 micrograms/kg; specific activity, 175-230 Ci/mol) as an intrajugular bolus. Blood samples were taken at various times between 5 and 90 min, and the plasma was analyzed by HPLC with gamma counting of fractions. *F-DOPA disappeared rapidly from plasma in concert with the formation of the 3-O-methylated metabolite, Me-*F-DOPA. Animals were killed from 5 to 120 min after injection, and the brains were rapidly dissected. The disappearance of *F-DOPA from both vermis and striatal samples was rapid. Me-*F-DOPA, the sole metabolite observed in the vermis, was the major labeled material in the striatum at greater than or equal to 20 min after injection. Fluorodopamine was an important metabolite in the striatum, making up 25% of total radioactivity at early intervals. Striatal samples also contained fluoro-3,4-dihydroxyphenylacetic acid, which constituted approximately 10% of the total radioactivity, and traces of two radiolabeled compounds, tentatively identified as fluorohomovanillic acid and fluoro-3-methoxytyramine.     

Synthesis and in vitro evaluation of [18F]fluoroethyl triazole labelled [Tyr3]octreotate analogues using click chemistry

A novel class of alkyne linked [Tyr³]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [¹⁸F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr³]octreotate analogues, G-TOCA (3a) and βAG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [¹⁸F]2-fluoroethyl triazole linked [Tyr³]octreotate analogues FET-G-TOCA (3b) and FET-βAG-TOCA (5b) under mild conditions and with short synthesis times (5 min at 20 °C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-βAG-TOCA have high affinity for the somatostatin receptor with IC₅₀ of 4.0 ± 1.4, and 1.6 ± 0.2 nM, respectively.     

Mechanistic Positron Emission Tomography Studies of 6-[18F]Fluorodopamine in Living Baboon Heart: Selective Imaging and Control of Radiotracer Metabolism Using the Deuterium Isotope Effect

Abstract: Mechanistic positron emission tomography (PET) studies using the deuterium isotope effect and specific pharmacological intervention were undertaken to examine the behavior of 6-[¹⁸F]fluorodopamine (6-[¹⁸F]FDA; 1 ) and (?)-6-[¹⁸F]fluoronorepinephrine {(?)-6-[¹⁸F]FNE; 2 } in the baboon heart. Two regiospecifically deuterated derivatives of 6-[¹⁸F]FDA [α,α-D₂(3 ) and β,β-D₂ (4 )] were used to assess the contributions of monoamine oxidase (MAO) and dopamine β-hydroxylase, respectively, to the clearance kinetics of 6-[¹⁸F]FDA. Compound 3 showed a reduced rate of clearance, consistent with MAO-catalyzed cleavage of the α C-D bond, whereas compound 4 showed no change, indicating that cleavage of the β C-D bond is not a rate-limiting step. Pretreatment with pargyline, an MAO inhibitor, also decreased the rate of clearance. Desipramine and tomoxetine [norepinephrine (NE) uptake inhibitors], but not GBR-12909 (a dopamine uptake inhibitor), blocked the uptake of both (?)-6-[¹⁸F]FNE and 6-[¹⁸F]FDA, with (?)-6-[¹⁸F]FNE showing a higher degree of blockade. Chiral HPLC demonstrated that 6-[¹⁸F]FDA is stereoselectively converted to (?)-6-[¹⁸F]FNE in vivo in the rat heart. These studies demonstrate that (a) the more rapid clearance of 6-[¹⁸F]FDA relative to (?)-6-[¹⁸F]FNE can be largely accounted for by metabolism by MAO; (b) selective deuterium substitution can be used to protect a radiotracer from metabolism in vivo and to favor a particular pathway; (c) 6-[¹⁸F]FDA and (?)-6-[¹⁸F]FNE share the NE transporter; (d) 6-[¹⁸F]FDA is stereoselectively converted to (?)-6-[¹⁸F]FNE in vivo; and (e) the profile of radioactivity in the heart for 6-[¹⁸F]FDA is complex, probably including labeled metabolites as well as neuronal and nonneuronal uptake.     

Intrastriatal Grafts of Fetal Mesencephalic Cell Suspensions in MPP+-Lesioned Rats: A Microdialysis Study In Vivo

The striatum of rats was lesioned by unilateral administration of MPP⁺. Two weeks later, a suspension of fetal mesencephalic cells (FMC), obtained from 14-day rat embryos, was injected into the lesioned striatum. Two weeks after grafting, the success of implantation and recovery of dopamine function were assessed by tyrosine hydroxylase immunocytochemistry (TH) and the measurement of striatal dopamine content. In addition, the extracellular concentrations of dopamine and dopamine metabolites were studied by microdialysis in vivo before and after perfusion of MPP⁺ to induce dopamine release from vesicular stores. TH+ cell bodies were seen in the lesioned grafted striata, indicating that fetal cells survived in these striata. In addition, there was a marked increase in TH-immunoreactivity in the neuronal fibers and terminals in the area surrounding the cell implant, suggesting a compensatory response of the host tissue which may involve fiber sprouting. Grafting induced a recovery in indices of dopamine function, including recovery in dopamine content, and basal and MPP⁺-induced dopamine release. Thus, grafts of FMC may provide a significant recovery of dopamine function in MPP⁺-lesioned striata.     

Motor behavior correlates with striatal [F]-DOPA uptake in MPTP-lesioned primates

The MPTP-lesioned monkey is considered as the best animal model for Parkinson’s disease (PD). It has damage to dopaminergic cell groups and motor dysfunction similar to that seen in PD. Correlations between these two parameters have been described but there is a lack of formal statistical analyses on dopaminergic function as assessed by [¹⁸F]-F-DOPA PET and objectively rated motor behavior in longitudinal experiments.     

Effect of N-Methyl-D-Aspartate and Potassium on Striatal Monoamine Metabolism in Immature Rat: An In Vivo Microdialysis Study

Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1–3 mM) and potassium (200–800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.     

No carrier added synthesis of O-(2'-[18F]fluoroethyl)-L-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine Schiff base

O-(2′-[¹⁸F]fluoroethyl)-l-tyrosine ([¹⁸F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of ¹⁸F (110 min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [¹⁸F]FET, based on NiII complex of a Schiff’s base of (S)-[N-2-(N′-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X = OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a–c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a–c (4.5–5.0 mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 °C for 5 min, followed by (2) removal of protective groups by treating with 0.5 M HCl (120 °C, 5 min). The major advantages of this procedure are retention of enantiomeric purity during the ¹⁸F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a–c. Radiochemically pure [¹⁸F]FET was isolated by semi-preparative HPLC (C18 μ-Bondapak, Waters) eluent aq 0.01 M CH₃COONH₄, pH 4/C₂H₅OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55 min. In a series of compounds 3a–c, tosyl derivative 3a provided highest radiochemical yield (40–45%, corrected for radioactive decay). Enantiomeric purity was 94–95% and 96–97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat’s tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.     

Fluorine-18 labeled galactosyl-neoglycoalbumin for imaging the hepatic asialoglycoprotein receptor

Asialoglycoprotein receptors (ASGP-R) are well known to exist on the mammalian liver, situate on the surface of hepatocyte membrane. Quantitative imaging of asialoglycoprotein receptors could estimate the function of the liver. ^99mTc labeled galactosyl-neoglycoalbumin (NGA) and diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) have been developed for SPECT imaging and clinical used in Japan. In this study, we labeled the NGA with ¹⁸F to get a novel PET tracer [¹⁸F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics. Methods: NGA was labeled with ¹⁸F by conjugation with N-succinimidyl-4-¹⁸F-fluorobenzoate ([¹⁸F]SFB) under a slightly basic condition. The in vivo metabolic stability of [¹⁸F]FNGA was determined. Ex vivo biodistribution of [¹⁸F]FNGA and blocking experiment was investigated in normal mice. MicroPET images were acquired in rat with and without block at 5 min and 15 min after injection of the radiotracer (3.7 MBq/rat), respectively. Results: Starting with ¹⁸F⁻ Kryptofix 2.2.2./K₂CO₃ solution, the total reaction time for [¹⁸F]FNGA is about 150 min. Typical decay-corrected radiochemical yield is about 8–10%. After rapid purified with HiTrap desalting column, the radiochemical purity of [¹⁸F]FNGA was more than 99% determined by radio-HPLC. [¹⁸F]FNGA was metabolized to produce [¹⁸F]FB-Lys in urine at 30 min. Ex vivo biodistribution in mice showed that the liver accumulated 79.18 ± 7.17% and 13.85 ± 3.10% of the injected dose per gram at 5 and 30 min after injection, respectively. In addition, the hepatic uptake of [¹⁸F]FNGA was blocked by pre-injecting free NGA as blocking agent (18.55 ± 2.63%ID/g at 5 min pi), indicating the specific binding to ASGP receptor. MicroPET study obtained quality images of rat at 5 and 15 min post-injection. Conclusion: The novel ASGP receptor tracer [¹⁸F]FNGA was synthesized with high radiochemical yield. The promising biological properties of [¹⁸F]FNGA afford potential applications for assessment of hepatocyte function in the future. It may provide quantitative information and better resolution which particularly help to the liver surgery.     

Incorporation and translocation of 2-deoxy-2-[18F]fluoro-d-glucose in Sorghum bicolor (L.) Moench monitored using a planar positron imaging system

[¹⁸F]FDG (2-deoxy-2-[¹⁸F]fluoro-d-glucose) was fed to a sorghum plant [Sorghum bicolor (L.) Moench] from the tip of a leaf and its movement was monitored using a planar positron imaging system (PPIS). [¹⁸F]FDG was uptaken from the leaf tip and it was translocated to the basal part of the shoots from where it moved to the roots, the tillers and the sheaths. Autoradiographic analysis of the distribution of ¹⁸F, [¹⁸F]FDG and/or its metabolites showed translocation to the roots, tillers, and to the leaves that were younger than the supplied leaf. Strong labelling was observed in the basal part of the shoots, in the sheaths, the youngest leaf and the root tips. Our results indicate that [¹⁸F]FDG and/or its metabolites were absorbed from the leaf and translocated to the sites where nutrients are required. This strongly suggests that [¹⁸F]FDG can be utilised as a tracer to study photoassimilate translocation in the living plant. This is the first report on the use of [¹⁸F]FDG, which is routinely used as a probe for clinical diagnosis, to study source to sink translocation of metabolites in whole plants in real time.     

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.     

4-[18F]Fluoro-L-m-Tyrosine: An L-3,4-Dihydroxyphenylalanine Analog for Probing Presynaptic Dopaminergic Function with Positron Emission Tomography

4-[18F]Fluoro-L-m-tyrosine (FMT), a biochemical probe of striatal dopaminergic function, has been synthesized as an L-3,4-dihydroxyphenylalanine analog for positron emission tomography. Biochemical characterization of this compound in the rat 30 min after intrajugular administration indicated that in the brain, selective decarboxylation occurred in the striatum, with the formation of 4-fluoro-3-hydroxyphenylethylamine and its metabolites. Positron emission tomography analysis of brain tissue in monkeys (Macaca nemestrina) after intravenous injection of FMT revealed a true time-dependent, specific accumulation of radioactivity in striatum, with a striatum/cerebellum (nonspecific) ratio of 4 at 180 min. Peripheral metabolism accounted for less than 40% of the total radioactivity in arterial blood samples after 120 min. The amino acid remained as the major component throughout the period of investigation (n = 3; 5 min, 95%; 10 min, 85%; 30 min, 67%; 60 min, 62%; 120 min, 60%), with a plasma clearance t 1/2 of 112 min. 3-O-Methylated metabolites were not observed. The substrate specificity of FMT, coupled with its limited in vivo peripheral metabolism, makes it a useful, new biochemical probe for in vivo, noninvasive evaluation of central dopaminergic mechanisms.     

Cerebral Metabolism of 6–[18F]Fluoro-l-3,4-Dihydroxyphenylalanine in the Primate

The tracers 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (6-[18F]fluoro-L-DOPA) and L-[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6-[18F]fluoro-L-DOPA was metabolized to 6-[18F]fluorodopamine, 3,4-dihydroxy-6-[18F]fluorophenylacetic acid, and 6-[18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of L-[14C]DOPA. 6-[18F]Fluorodopamine was synthesized faster than [14C]dopamine. In the frontal cortex, the major metabolite was also 6-[18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3-O-methyl-6-[18F]fluoro-L-DOPA. On the basis of these data, the images obtained with 6-[18F]fluoro-L-DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms.     

<Superscript>18</Superscript>F-labeled tyrosine derivatives: Synthesis and experimental studies on accumulation in tumors and abscesses

Tyrosine derivatives labeled with a short-lived fluorine-18 isotope (T _1/2 110 min), namely 2-[¹⁸F]fluoro-L-tyrosine (FTYR) and O-(2′-[¹⁸F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceuticals (RPs) for positron emission tomography (PET), were obtained by asymmetric syntheses. Accumulation of FTYR and FET in the rat tumor “Glioma 35 rats tumor” and in abscesses induced in Wistar rats muscles was studied and compared with that of a well-known glycolysis radiotracer 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG). It was shown that the relative accumulation indices of amino acid RPs were considerably lower than those of FDG. At the same time, tumor/muscle ratios were high enough (2.9 for FET and 3.9 for FTYR 120 min after injection) for reliable tumor visualization. The data obtained indicated a possibility in principle to use FTYR and FET for differentiated PET diagnostics of brain tumors and inflammation lesions. Of the tyrosine derivatives studied, FET seems to be the most promising agent due to a simple and easily automated method of preparation based on direct nucleophilic substitution of the leaving tosyloxy group of an enantiomerically pure Ni-(S)-BPS-(S)-Tyr(CH₂CH₂OTs) precursor by an activated [¹⁸F]fluoride.     

In Vivo Voltammetric Study of 6-Hydroxydopamine-Induced Neuronal Degradation

Freely moving rats were injected intraventricularly with 200 micrograms of 6-hydroxydopamine (6-OHDA) and examined for transport of this substance to the striatum, degradation of dopamine (DA) neurons, and functional recovery through microcomputer-controlled in vivo voltammetry. Approximately 6 min after the injection, 6-OHDA began to appear in the extracellular fluid of the contralateral striatum. It increased linearly and began to decrease exponentially with the termination of the injection. Two hours after the injection with 6-OHDA, a peak began to appear at the same potential as the peak of DA in the differential pulse voltammogram. It persisted for approximately 3 days. When the rats were injected intraperitoneally with L-3,4-dihydroxyphenylalanine (L-Dopa), the conversion of L-Dopa to DA was not found 1 week after the 6-OHDA injection, but was clearly recognized 5 months after the injection. When the rats were examined for behavioral changes arising from the L-Dopa injection, they were found to be clearly less hyperactive 5 months after the 6-OHDA injection than 1 week after.     

Two-step regio- and stereoselective syntheses of [19F]- and [18F]-2-deoxy-2-(R)-fluoro-beta-D-allose

Replacement of specific hydroxyl groups by fluorine in carbohydrates is an ongoing challenge from chemical, biological, and pharmaceutical points of view. A rapid and efficient two-step, regio- and stereoselective synthesis of 2-deoxy-2-(R)-fluoro-beta-d-allose (2-(R)-fluoro-2-deoxy-beta-d-allose; 2-FDbetaA), a fluorinated analogue of the rare sugar, d-allose, is described. TAG (3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol or 3,4,6-tri-O-acetyl-d-glucal), was fluorinated in anhydrous HF with dilute F(2) in a Ne/He mixture or with CH(3)COOF at -60 degrees C. The fluorinated intermediate was hydrolyzed in 1N HCl and the hydrolysis product was purified by liquid chromatography and characterized by 1D (1)H, (13)C, and (19)F NMR spectroscopy as well as 2D NMR spectroscopy and mass spectrometry. In addition, (18)F-labeled 2-deoxy-2-(R)-fluoro-beta-d-allose (2-[(18)F]FDbetaA) was synthesized for the first time, with an overall decay-corrected radiochemical yield of 33+/-3% with respect to [(18)F]F(2), the highest radiochemical yield achieved to date for electrophilic fluorination of TAG. The rapid and high radiochemical yield synthesis of 2-[(18)F]FDbetaA has potential as a probe for the bioactivity of d-allose.     

Imaging the Dopamine Uptake Site with Ex Vivo [18F]GBR 13119 Binding Autoradiography in Rat Brain

We studied the binding of [18F]GBR 13119 (1-[[(4-[18F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum greater than nucleus accumbens = olfactory tubercle greater than substantia nigra = ventral tegmental area greater than other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site. Unilateral 6-hydroxy-dopamine lesions of dopamine neurons caused a marked decrease in striatal and nigral binding on the side of the lesion. We conclude that intravenous injection of [18F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.