Abstract Positron emission tomography (PET) is a powerful and rapidly developing technology that plays key roles in medical imaging, including the research of Alzheimer’s disease. Despite the exceptional promise of PET imaging, the availability of PET agents is limited in many situations due to the lack of efficient and simple labeling methods to modify biologically active small molecules/drugs. Based on the highly innovative photoredox systems described by the Nicewicz group, Li, Wu and Nicewicz have made the first breakthrough on direct arene C–H fluorination with 18F- that allows direct conversion of drugs to PET agents; followed by SNAr radiofluorination that could precisely control the radiofluorination position on aromatic substrates. This new method indeed provide us access to agents that are previously challenging or impossible to synthesize. Based on the Nucleophilic Aromatic Substitution we just developed, initial success was made on the synthesis of innovative PET agents for synapse density imaging. Affecting 6 million people in the USA, Alzheimer’s disease (AD) is increasingly viewed as a malignancy that progressed from preclinical AD, to mild cognitive impairment (MCI), and to AD. Because synapses are crucial for cognitive function, synaptic loss has been observed as a promising prognosis marker in AD patients. The ability to monitor synaptic density in vivo would therefore be important in AD patient management. Based on the critical need of synapse density imaging and our initial success, we will validate the new agents in normal and AD animals in this supplement. The success of this approach could not only lead to new PET agents for AD patients, but also increase the availability of the PET agent due to simpler and milder reaction conditions. Two aims are proposed here. In Aim 1, we will establish the radiochemistry of 18F-UCB agents for synapse density imaging. In order to make the agent widely available to the field with low cost, we will also develop LED light based synthetic method for our UCB agents. In Aim 2, we will characterize the sensitivity of our 18F-UCB agent in normal and AD mice. In summary, photoredox reactions are entirely new methods for the incorporation of [18F]F into aromatic compounds. The mild conditions coupled with easy access to the required precursors will allow for the unprecedented access to novel aromatic [18F] PET tracers for use in neurology. The goal of this supplement is to develop and validate innovative PET agents to image synaptic loss in AD model based on our newly developed labeling method.