Search

UnlabelledFully automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of PET tracers made under current good manufacturing practice guidelines. There is a current trend toward supporting kitlike disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers because of pressure, temperature, and chemical compatibility considerations. This study demonstrated the versatile use of the ELIXYS fully automated radiosynthesizer to adapt and produce 8 different (18)F-labeled PET tracers of varying complexity.MethodsThree-reactor syntheses of 2-deoxy-2-(18)F-fluoro-β-d-arabinofuranosylcytosine (d-(18)F-FAC), 2-deoxy-2-(18)F-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-(18)F-FMAU), and 2-deoxy-2-(18)F-fluoro-5-ethyl-β-d-arabinofuranosyluracil (d-(18)F-FEAU) along with the 1-reactor syntheses of d-(18)F-FEAU, (18)F-FDG, 3-deoxy-3-(18)F-fluoro-l-thymidine ((18)F-FLT), (18)F-fallypride, 9-(4-(18)F-fluoro-3-hydroxymethylbutyl)-guanine ((18)F-FHBG), and N-succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB), were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted and slightly modified from those in the literature but were not fully optimized. Furthermore, (18)F-FLT, (18)F-FDG, and (18)F-fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing severe combined immunodeficient mice and wild-type BALB/c mice. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests.ResultsAll tracers were produced with radiochemical yields comparable to those in the literature. (18)F-FLT, (18)F-FDG, and (18)F-fallypride were successfully used to image the mice, with results consistent with those reported in the literature. All tracers that were subjected to clinical quality control tests passed.ConclusionThe ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple (18)F-labeled PET tracers suitable for clinical applications using the same hardware setup.

Acetylcholinesterase inhibitors (AChEIs) are drugs that increase synaptic acetylcholine (ACh) concentrations and are under investigation as treatments for symptoms accompanying Alzheimer's disease. The goal of this work was to use PET imaging to evaluate alterations of in vivo α4β2 nicotinic acetylcholine receptor (nAChR) binding induced by the AChEIs physostigmine (PHY) and galanthamine (GAL). The α4β2 nAChR-specific radioligand [(18)F]nifene was used to examine the effects of 0.1-0.2 mg/kg PHY, 5 mg/kg GAL, and saline in three separate experiments all performed on each of two rat subjects. A 60-min bolus-infusion protocol was used with drug administered after 30 min. Data from the thalamus and cortex were analyzed with a graphical model accounting for neurotransmitter activation using the cerebellum as a reference region to test for transient competition with bound [(18) F]nifene. Significant [(18) F]nifene displacement was detected in both regions during one PHY and both GAL studies, while no significant competition was observed in both saline studies. This preliminary work indicates the viability of [(18) F]nifene in detecting increases in synaptic ACh induced by AChEIs.

An experiment that highlights the role electrochemistry plays in the fabrication of nanoscale structures is presented. The movement and alignment of the nickel nanowires were observed, when manipulated using magnetic fields through the lens of an optical microscope using common magnets to alter the applied magnetic field.

Fully automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of PET tracers made under current good manufacturing practice guidelines. There is a current trend toward supporting kitlike disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers because of pressure, temperature, and chemical compatibility considerations. This study demonstrated the versatile use of the ELIXYS fully automated radiosynthesizer to adapt and produce 8 different 18F-labeled PET tracers of varying complexity. Methods: Three-reactor syntheses of 2-deoxy-2-18F-fluoro-P-D-arabinofuranosylcytosine (D-18F-FAC), 2-deoxy-2-18F-fluoro-5-methyl-p-L-arabinofuranosyluracil (L-18F-FMAU), and 2-deoxy-2-18F-fluoro-5-ethyl-p-D-arabinofuranosyluracil (D-18F-FEAU) along with the 1-reactor syntheses of D-18F-FEAU, 18F-FDG, 3-deoxy-3-18F-fluoro-L-thymidine (18F-FLT), 18F-fallypride, 9-(4-18F-fluoro-3-hydroxymethylbutyl)-guanine (18F-FHBG), and N-succinimidyl-4-18F-fluorobenzoate (18F-SFB), were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted and slightly modified from those in the literature but were not fully optimized. Furthermore, 18F-FLT, 18F-FDG, and 18F-fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing severe combined immunodeficient mice and wild-type BALB/c mice. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests. Results: All tracers were produced with radiochem-ical yields comparable to those in the literature. 18F-FLT, 18F-FDG, and 18F-fallypride were successfully used to image the mice, with results consistent with those reported in the literature. All tracers that were subjected to clinical quality control tests passed. Conclusion: The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple 18F-labeled PET tracers suitable for clinical applications using the same hardware setup. [ABSTRACT FROM AUTHOR]

Presents a response by the authors to a letter to the editor about their article "Template Synthesis and Magnetic Manipulation of Nickel Nanowires" in the May 2005 issue of the "Journal of Chemical Education."

Abstract: Lobeline is a potential smoking cessation drug with affinity for the α4β2 nicotinic acetylcholine receptor and may inhibit the blood–brain barrier (BBB) amine transporter. The goal of this work was to use PET imaging to evaluate the effects of lobeline on the kinetic properties of [18F]nifene in the rat brain. Methods: Direct α4β2* competition of lobeline with [18F]nifene was evaluated using imaging experiments with both displacing and blocking doses of lobeline (1mg/kg, i.v.) given between two injections of [18F]nifene separated by 50min. Inhibition of the BBB amine transporter was examined using a separate imaging protocol with three injections of [18F]nifene, first at baseline, then following (−)nicotine blocking, and finally following lobeline blocking. Results: Rapid displacement of [18F]nifene was observed in the α4β2*-rich thalamus following lobeline administration, suggesting direct competition of the drug at α4β2* sites. Slight decreases in BBB transport of [18F]nifene were observed when the α4β2* system was first saturated with (−)nicotine and then given lobeline. This perturbation may be due to inhibition of the BBB amine transporter by lobeline or reductions in blood flow. Significant cerebellar displacement of [18F]nifene was found following the administration of both lobeline and (−)nicotine, indicating detectable specific binding in the rat cerebellum. Conclusion: The competition of lobeline with [18F]nifene is largely dominated at the α4β2* binding site and only small perturbations in BBB transport of [18F]nifene are seen at the 1mg/kg dose. Similar experiments could be used to study other drugs as therapeutic agents for smoking cessation with PET. [Copyright &y& Elsevier]

Positron emission tomography (PET) phantoms are used to calibrate PET scanners so that inter-scanner and inter-isotope comparison can be made between PET datasets. Hot rod style phantoms have a hole pattern, which is filled with a positron-emitting isotope and typically involves using two radioisotope reservoirs with the pattern created with channels in between. However, this configuration is difficult to fill and requires an excess of activity and volume. Here we present an alternative design, a phantom that is linearly filled-one channel at a time. The process of fabrication of prototypes of the design is described and PET images of the prototyped phantom are also shown for a variety of commonly used radioisotopes ((52)Mn, (64)Cu, (76)Br, (124)I). This design allows for a large reduction in isotope volume and required filling time making a quality assurance (QA) protocol safer, more efficient and less costly.