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Positron Emission Tomography (PET) imaging is a powerful non-invasive imaging modality used to quantify biochemical processes in vivo. The work described in this thesis encompasses two aspects of PET radiochemistry: (1) the development of new chemical methodology applying the principles of green chemistry to late-stage 18F-fluorination, and (2) developing a PET radioligand for the dopamine D3 receptor. (1) As a way to simplify FDA mandated quality control and residual solvent analysis prior to the release of PET radiopharmaceuticals we sought to apply the principles of green chemistry to 18F-radiochemistry. Green radiochemistry in late-stage stage 18F-fluorination with [18F]KF employs ethanol and ethanol/water mixtures as the only solvents used throughout the entire radiopharmaceutical production: azeotropic drying, nucleophilic fluorination, purification and formulation. This work developed a method in which using ethanol in place of acetonitrile is a viable option for azeotroptic drying of [18F]fluoride. Furthermore, it demonstrated that aliphatic 18F-fluorination reactions can proceed in an optimized 15% water, 85% ethanol mixture. Proof of concept was demonstrated through the synthesis of clinically relevant PET radiopharmaceuticals. The new methodology described challenges the long held belief that nucleophilic fluorination reactions cannot proceed in protic solvents or aqueous media, and encourages further exploration into the utility of green fluorine chemistry. (2) Dopamine is a monoamine neurotransmitter in the Central Nervous System (CNS), and its signaling is mediated by pre-synaptic and post-synaptic dopamine receptors. These are D1-like (D1 and D5) and D2-like (D2, D3, D4) receptors, which are G protein-coupled receptors (GPCRs) and are classified based on these two subfamilies due to sequence homology and pharmacological similarities. The D3 receptor is implicated in many neurological and neurodegenerative diseases and disorders, including substance abuse, depression and schizophrenia. Significant efforts have gone into developing ligands as therapeutics, and as positron emission tomography (PET) diagnostics at this receptor. Significant challenges to this pursuit include the high sequence homology between the D2 and D3 receptors, and the physicochemical properties associated with BBB permeability and in vivo stability, while maintaining selectivity at this receptor. The synthesis and initial evaluation of a series of new carbon-11 and fluorine-18 PET radioligands for the D3 receptor is described. These radioligands are based on known ligands with good selectivity for the D3 receptor (pramipexole and BP897). Due to stability issues when using pramipexole-containing scaffolds, BP897 derivatives containing a naphthamide moiety were developed and evaluated in vitro using rad brain autoradiography, and in vivo using rodent microPET imaging. A carbon-11 D3-selective compound was synthesized and identified as a promising candidate, owing to its high affinity for D3 receptors, selectivity for D3 over D2 receptors, and good blood-brain barrier (BBB) penetration. Further evaluation and optimization of the scaffold is merited prior to clinical translation in the future.