From in†situ to in vivo: an in†situ click-chemistry-derived carbonic anhydrase†II imaging agent for positron emission tomography.

CA II makes a good PET: Discovering positron emission tomography (PET) probes with high target affinities is challenging. PET probe discovery using in situ click chemistry uses (19) F-bearing fragments as (18) F surrogates. This ensures that the lead hits and PET probes have equivalent chemical or biological characteristics, making PET probe discovery predictable and reliable.

Highlighting the Versatility of the Tracerlab Synthesis Modules. Part 1: Fully Automated Production of [F]Labelled Radiopharmaceuticals using a Tracerlab FX(FN).

The field of radiochemistry is moving towards exclusive use of automated synthesis modules for production of clinical radiopharmaceutical doses. Such a move comes with many advantages, but also presents radiochemists with the challenge of re-configuring synthesis modules for production of radiopharmaceuticals that require non-conventional radiochemistry whilst maintaining full automation. This review showcases the versatility of the Tracerlab FX(FN) synthesis module by presenting simple, fully automated methods for producing [(18)F]FLT, [(18)F]FAZA, [(18)F]MPPF, [(18)F]FEOBV, [(18)F]sodium fluoride, [(18)F]fluorocholine and [(18)F]SFB.

Design and optimization of coin-shaped microreactor chips for PET radiopharmaceutical synthesis.

UNLABELLED: An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. METHODS: The unique architecture of the device is centered around a 5-microL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. RESULTS: The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. CONCLUSION: The reactor has the potential to produce multiple human doses of (18)F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment.

High-yield, automated radiosynthesis of 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) ready for animal or human administration.

The biomarker 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([(18)F]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [(18)F]FDDNP--along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)--are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with K(18)F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [(18)F]FDDNP in high radiochemical yields (40-60%; n> 120), with specific activities ranging from 4 to 8 Ci/mumol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [(18)F]fluoride) of [(18)F]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.

Drugs and probes: the symbiotic relationship between pharmaceutical discovery and imaging science.

Pharmaceutical research and imaging science are becoming increasingly intertwined. Positron emission tomography (PET) is a molecular imaging technique with particularly broad application in drug discovery and development. At the same time, modern techniques of drug discovery are helping accelerate the development of new PET probes. This article describes the relationship between the two fields, with particular consideration of practical and strategic limitations to full utilization of available technology.