It has been observed that microfluidic chips used for synthesizing 18F-labeled compounds demonstrate visible light emission without nearby scintillators or fluorescent materials. The origin of the light was investigated and found to be consistent with the emission characteristics from Cerenkov radiation. Since 18F decays through the emission of high-energy positrons, the energy threshold for beta particles, i.e., electrons or positrons, to generate Cerenkov radiation was calculated for water and polydimethylsiloxane (PDMS), the most commonly used polymer-based material for microfluidic chips. Beta particles emitted from 18F have a continuous energy spectrum, with a maximum energy that exceeds this energy threshold for both water and PDMS. In addition, the spectral characteristics of the emitted light from 18F in distilled water were also measured, yielding a broad distribution from 300 nm to 700 nm, with higher intensity at shorter wavelengths. A photograph of the 18F solution showed a bluish-white light emitted from the solution, further suggesting Cerenkov radiation. In this study, the feasibility of using this Cerenkov light emission as a method for quantitative measurements of the radioactivity within the microfluidic chip in situ was evaluated. A detector previously developed for imaging microfluidic platforms was used. The detector consisted of a charge coupled device (CCD) optically coupled to a lens. The system spatial resolution, minimum detectable activity and dynamic range were evaluated. In addition, a calibration of Cerenkov signal versus activity concentration in the microfluidic chip was determined. This novel method of Cerenkov radiation measurements will provide researchers with a simple yet robust quantitative imaging tool for microfluidic applications utilizing beta particles.

Combining the specificity of tumor-targeting antibodies with the sensitivity and quantification offered by positron emission tomography (PET) provides tremendous opportunities for molecular characterization of tumors in vivo. Until recently, significant challenges have been faced when attempting to combine antibodies which show long biological half-lives and positron-emitting radionuclides with comparably short physical half-lives, in particular (18)F (half-life, 109 min). A fast and simple microwave-assisted method of generating N-succinimidyl-4-[(18)F]fluorobenzoate has been developed and employed for radiolabeling a small, rapidly targeting HER2-specific engineered antibody fragment, the cys-diabody. Using this tracer, HER2-positive tumor xenografts in mice were detected at 1-4 h post-injection by microPET. This confirms the rapid kinetics of [(18)F]fluorobenzoyl cys-diabody localization, and demonstrates the feasibility of same-day immunoPET imaging. This approach can be broadly applied to antibodies targeting cell surface biomarkers for molecular imaging of tumors and should be highly translatable for clinical use.

Methods for tagging biomolecules with F-18 as immuno-Positron Emission Tomography (immunoPET) tracers require tedious optimization of radiolabeling conditions, and can consume large amounts of scarce biomolecules. We describe an improved method utilizing a digital microfluidic droplet generation (DMDG) chip which provides computer controlled metering and mixing of 18F-tag, biomolecule, and buffer in defined ratios, allowing rapid scouting of reaction conditions in nanoliter volumes. The identified optimized conditions were then translated to bench-scale 18F-labeling of a cancer-specific engineered antibody fragments, enabling microPET imaging of tumors in xenografted mice at 0.5–4 h post injection.

Four different no carrier added (n.c.a.) 4‐[18F]fluorophenylurea derivatives are synthesized as model compounds via two alternative routes. In both cases carbamate‐4‐nitrophenylesters are used as intermediates. Either n.c.a. 4‐[18F]fluoroaniline reacts with carbamates of several amines, or the carbamate of n.c.a. 4‐[18F]fluoroaniline is formed at first and an amine is added subsequently to yield the urea derivative. The choice of the appropriate way of reaction depends on the possibilities of precursor synthesis.The radiochemical yields reach up to 80% after 50 min of synthesis time while no radiochemical by‐products can be determined. These high yields were possible due to an optimized preparation of n.c.a. 4‐[18F]fluoroaniline with a radiochemical yield of up to 90%. From the various ways of its radiosynthesis, the substitution with n.c.a. [18F]fluoride on dinitrobenzene is chosen, using phosphorous acid and palladium black for reduction of the second nitro group. Copyright © 2006 John Wiley & Sons, Ltd.

We present a plug-and-play radiosynthesis platform and accompanying computer software based on modular subunits that can easily and flexibly be configured to implement a diverse range of radiosynthesis protocols. Modules were developed that perform: (i) reagent storage and delivery, (ii) evaporations and sealed reactions, and (iii) cartridge-based purifications. The reaction module incorporates a simple robotic mechanism that removes tubing from the vessel and replaces it with a stopper prior to sealed reactions, enabling the system to withstand high pressures and thus provide tremendous flexibility in choice of solvents and temperatures. Any number of modules can rapidly be connected together using only a few fluidic connections to implement a particular synthesis, and the resulting system is controlled in a semi-automated fashion by a single software interface. Radiosyntheses of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), 1-[18F]fluoro-4-nitrobenzene ([18F]FNB), and 2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyl cytosine (D-[18F]FAC) were performed to validate the system and demonstrate its versatility.

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