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Positron emission tomography (PET) is a widely-used nuclear medicine imaging technique for assessing biodistribution of drugs, diagnosing diseases, and monitoring therapy response. The rapid development of new PET tracers in both research and clinical applications (to image new targets) demands new advances in radiolabeling techniques to facilitate the frequent production of diverse tracers. Recent developments in droplet-based radiochemistry have shrunk reaction volumes 100x (i.e. to 2x higher radiochemical yield and >3x activity yield, while consuming 34-200x less reagents. Moreover, to establish the clinical relevance of droplet-based radiochemistry, we developed various droplet-based scale-up approaches including (i) iteratively loading and evaporating [18F]fluoride aliquots in a single droplet reaction, (ii) pre-concentrating [18F]fluoride in a miniature cartridge compatible with a single reaction site, and (iii) pooling multiple droplet reactions for on-demand dose. These methods, validated for reliability and versatility, successfully delivered clinically-relevant doses of [18F]FET (an amino acid tracer), [18F]Florbetaben (an amyloid imaging agent), [18F]FBnTP, isotopic exchange fluorinated compounds, and aluminum-[18F]fluoride probes. Apart from droplet-based radiosynthesis techniques, I also pursued other novel radiochemistry systems. I helped to develop a platform for microvolume reactions, featuring a pipettor on an XYZ motion gantry and a disposable cassette with integrated micro-vial. The versatile setup performs operations like trapping/releasing [18F]fluoride, liquid transfers, and lid installation/removal for reactor. Comprehensive experiments have been conducted to characterize the system and demonstrate the radiosynthesis feasibility, using [18F]Fallypride as an example. I also helped develop a novel electrochemical radiofluorination (ECRF) technique using a spilt bipolar electrode (s-BPE) for electron-rich compounds such as thioether derivatives. Unlike traditional ECRF which requires high salt concentration, this s-BPE system, with its dual conductive materials, facilitates anodic and cathodic reactions at lower salt concentrations. We achieved a 5x increase in molar activity for [18F]fluoromethyl (methylthio)acetate compared to conventional ECRF approaches, mainly attributed to reduced [19F]F- contamination from less salt. Radiochemistry in droplets and electrochemistry for [18F]fluoride labeling showcased an innovative optimization approach and scalable method for clinically-relevant production, surpassing conventional methods. The methodologies outlined in this dissertation provide a comprehensive pathway to speed up the transition of both established and novel PET tracers from the laboratory to clinical application swiftly and cost-effectively.

Two novel synthetic routes to formation of gold-magnetite nanoparticles have been designed. Treatment of preformed magnetite nanoparticles with ultrasound in aqueous media with dissolved tetrachloroauric acid resulted in the formation of gold-magnetite nanocomposite materials. The other route involved irradiation of preformed magnetite nanoparticles by UV light in aqueous media with dissolved tetrachloroauric acid. This method resulted in the formation of gold-magnetite nanocomposite materials. These materials maintained the morphology of the original magnetite particles. The morphology of the gold particles could be controlled by adjusting experimental parameters, like addition of small amounts of solvent modifiers such as methanol, diethylene glycol, and oleic acid as well as variation of the concentration of the tetrachloroauric acid solution and time of the reaction. The nanocomposite materials were magnetic and exhibited optical properties similar to gold nanoparticles. Since we were not able to directly synthesize core shell gold magnetite nanoparticles, TiO2 was used as a bridging material. TiO2 nanoparticles with embedded magnetite were suspended in aqueous HAuCl4 and irradiated with ultraviolet light to photodeposit gold. The degree of gold coating and the wavelength of absorbance could be controlled by adjusting concentration of HAuCl4. Absorbance maxima were between 540-590 nm. Particles exhibited superparamagnetic properties (blocking temperature ~170 K) whether or not coated with gold. These particles have potential applications as drug delivery agents, magnetic imaging contrast agents, and magnetically separatable photocatalysts with unique surface properties. Another goal was to synthesize and characterize indium doped magnetite nanoparticles for application as radiotracers for in vivo fate studies. The labeled particles will be useful for determination of pharmacological behavior in biological systems. Indium doped magnetite particles with varying size and surface chemistry were synthesized with wet chemical techniques. The synthesized nanoparticles were characterized in terms of the size and shape with the help of TEM, the elemental composition by ICP and EDS, the crystal structure by XRD and magnetic properties by SQUID measurements. It was found that the indium loading could be controlled even though the magnetic properties were similar to undoped magnetite.

The dosimetry of new positron emitting radiopharmaceuticals is initially estimated using animal tissue and organ biodistributions assessed in vitro. Such methods are time and labor intensive and can have limited accuracy. This research investigated two alternative methods by which biodistribution can be obtained from the laboratory rat: in vitro organ measurements using a reduced sacrifice technique, and in vivo measurements using single photon emission computed tomography (SPECT). As an alternative to a four time-point sacrifice method, a two time-point method was evaluated as a means to determine the organ cumulated activity of $\sp{11}$C labeled radiopharmaceuticals. Residence times calculated using two time-points acquired during the first half-life of $\sp{11}$C were either equivalent or larger than those resulting from using four sacrifice times. Correction factors were required for the urinary bladder and gallbladder when using this simplified technique due to delayed uptakes. In vivo assessments were performed with SPRINT, a full ring detector SPECT system using a slit aperture to obtain a 3-to-1 object to image magnification ratio. Acceptable resolution for 511 keV photons was achieved using a high energy parallel slice collimator and a novel technique to correct for penetration of the slit aperture by high energy photons. The resulting system resolution was approximately 4.5 mm axially and transaxially. System sensitivity was $\sim$55 cpm/$\mu$Ci, a consequence of high resolution collimation and poor intrinsic detector efficiency. Qualitative and quantitative high energy imaging was performed using two-dimensional and three-dimensional phantoms and live rats injected with ($\sp{18}$F) fluorodeoxyglucose. Phantoms displayed well resolved hot and cold objects, and animal images showed good contrast of the brain and heart regions. Hot phantom regions and animal organs were quantified with an accuracy of $\pm$8% of the known activity, with a standard deviation of $\pm$15%. Accurate determination of region activity required substantial activity concentrations (${\sim}100\ \mu$Ci/ml) and imaging times of one hour. Analysis of animal biodistributions using a reduced sacrifice protocol provides results in good agreement with and generally conservative to results using all sacrifice intervals. Animal biodistributions assessed in vivo with slit aperture SPECT can show good accuracy for organs with substantial uptakes, but the method is hindered by very poor system sensitivity.