Synthesis of N‐tert ‐butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) for in vivo detection of free radicals

We have synthesized the fluorine‐18 labeled derivative of N ‐ tert ‐butyl‐α‐phenylnitrone (PBN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N ‐ tert ‐Butyl‐α‐(4‐[ 18 F]fluorophenyl)‐nitrone ([ 18 F]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N ‐ tert ‐butyl‐α‐(4‐nitrophenyl)nitrone with [ 18 F]fluoride. An alternate two step synthesis route consisted of the nucleophilic [ 18 F]fluoride substitution of 4‐ N , N , N ‐trimethylammoniumbenzaldehyde triflate to yield 4‐[ 18 F]fluorobenzaldehyde, which was distilled into a vial containing N ‐ tert ‐butyl‐hydroxylamine in 2N NaOH. 4‐[ 18 F]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [ 18 F]FPBN. [ 18 F]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time < 45 min. and was suitable for further applications in in vivo studies of free radicals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90158/1/2580360202_ftp.pd

(−)‐[ 18 F]Flubatine: evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101867/1/jlcr3069.pd

Regional brain distribution of [18F]GBR 13119, a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice

We have examines the regional brain distribution of [18F]GBR 13119 (18F: [beta]+, T1/2 = 110 min), a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice. High levels of binding are observed in the striatum of both species, with striatum/cerebellum ratios of 3-4 at 60 min after injection of the radiotracer. Striatum radioactivity and striatum/cerebellum ratios are more than 50% reduced in C57BL/6 mice treated chronically with the neurotoxin MPTP. We conclude mice are an appropriate model for the in vivo study of the dopamine uptake system, and that [18F]GBR 13119 may be a suitable in vivo marker for degeneration of striatal dopaminergic neurons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27847/1/0000258.pd

Routine production of 2-deoxy-2-[18F]fluoro--glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin

Resin-supported [18F]fluoride ion has been prepared and applied to a rapid, convenient synthesis of [18F]FDG. "No-carrier-added" [18F]fluoride ion is collected on a quaternary 4-(N, N-dialkylamino)-pyridinium functionalized polystyrene anion exchange resin directly from a [18O]water target, dried by rinsing with acetonitrile, and then reacted with 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-[beta]--mannopyrannose. Acidic hydrolysis yields [18F]FDG in a synthesis time of 40 min with overall yields presently averaging above 50%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28859/1/0000694.pd

A captive solvent method for rapid N-[11C]methylation of secondary amides: Application to the benzodiazepine, 4'-chlorodiazepam (RO5-4864)

[11C]4'-Chlorodiazepam (RO5-4864), for PET studies of peripheral benzodiazepine receptors, was synthesized by alkylation of 1-desmethyl-4'-chlorodiazepam, in a small volume of acetone adsorbed on acrylic yarn, with [11C]methyl iodide in the injection loop of a liquid chromatograph. The reaction mixture was introduced directly onto a small, disposable alumina chromatographic column. Elution with pentane:ethanol gave a product of high chemical and radiochemical purity. A simple heating and cooling device for the injection loop is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27565/1/0000609.pd

Optimised Motion Tracking for Positron Emission Tomography Studies of Brain Function in Awake Rats

Positron emission tomography (PET) is a non-invasive molecular imaging technique using positron-emitting radioisotopes to study functional processes within the body. High resolution PET scanners designed for imaging rodents and non-human primates are now commonplace in preclinical research. Brain imaging in this context, with motion compensation, can potentially enhance the usefulness of PET by avoiding confounds due to anaesthetic drugs and enabling freely moving animals to be imaged during normal and evoked behaviours. Due to the frequent and rapid motion exhibited by alert, awake animals, optimal motion correction requires frequently sampled pose information and precise synchronisation of these data with events in the PET coincidence data stream. Motion measurements should also be as accurate as possible to avoid degrading the excellent spatial resolution provided by state-of-the-art scanners. Here we describe and validate methods for optimised motion tracking suited to the correction of motion in awake rats. A hardware based synchronisation approach is used to achieve temporal alignment of tracker and scanner data to within 10 ms. We explored the impact of motion tracker synchronisation error, pose sampling rate, rate of motion, and marker size on motion correction accuracy. With accurate synchronisation (<100 ms error), a sampling rate of >20 Hz, and a small head marker suitable for awake animal studies, excellent motion correction results were obtained in phantom studies with a variety of continuous motion patterns, including realistic rat motion (<5% bias in mean concentration). Feasibility of the approach was also demonstrated in an awake rat study. We conclude that motion tracking parameters needed for effective motion correction in preclinical brain imaging of awake rats are achievable in the laboratory setting. This could broaden the scope of animal experiments currently possible with PET

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

We studied the binding of [ 18 F]GBR 13119 {1-[[(4-[ 18 F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine} to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum > nucleus accumbens = olfactory tubercle > sub-stantia nigra = ventral tegmental area > 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 [ 18 F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66209/1/j.1471-4159.1990.tb04178.x.pd

Biotransformation of lanthanum by Aspergillus niger

Lanthanum is an important rare earth element and has many applications in modern electronics and catalyst manufacturing. However, there exist several obstacles in the recovery and cycling of this element due to a low average grade in exploitable deposits and low recovery rates by energy-intensive extraction procedures. In this work, a novel method to transform and recover La has been proposed using the geoactive properties of Aspergillus niger. La-containing crystals were formed and collected after A. niger was grown on Czapek-Dox agar medium amended with LaCl 3. Energy-dispersive X-ray analysis (EDXA) showed the crystals contained C, O, and La; scanning electron microscopy revealed that the crystals were of a tabular structure with terraced surfaces. X-ray diffraction identified the mineral phase of the sample as La 2(C 2O 4) 3·10H 2O. Thermogravimetric analysis transformed the oxalate crystals into La 2O 3 with the kinetics of thermal decomposition corresponding well with theoretical calculations. Geochemical modelling further confirmed that the crystals were lanthanum decahydrate and identified optimal conditions for their precipitation. To quantify crystal production, biomass-free fungal culture supernatants were used to precipitate La. The results showed that the precipitated lanthanum decahydrate achieved optimal yields when the concentration of La was above 15 mM and that 100% La was removed from the system at 5 mM La. Our findings provide a new aspect in the biotransformation and biorecovery of rare earth elements from solution using biomass-free fungal culture systems. </p