Project Summary Adoptive cell transfer (ACT) immunotherapy holds great promise in treating various diseases, including cancer and neurodegenerative disorders like Lewy Body Dementia (LBD). A critical challenge in advancing ACT therapies is the non-invasive tracking of therapeutic cells to assess their effectiveness and safety. The parent R01 (R01EB031224) focuses on leveraging Magnetic Particle Imaging (MPI) for tracking ACT T cells in cancer therapies. This Administrative Supplement aims to extend this work to track Molecular Guided T Cell Therapy (MCT) in preclinical models of LBD, a neurodegenerative condition with no current disease-modifying interventions. Two primary aims are proposed: Aim 1. Evaluate the Dynamics of MCT Trafficking in a Preclinical Model of LBD: This aim focuses on using MPI tracers developed under the parent R01 to label MCT cells, facilitating non-invasive tracking of these cells in the brain. The goal is to understand how MCT cells distribute and persist in target regions, thereby providing insights into their therapeutic potential. Aim 2. Correlate MPI Signal to α-Synuclein Pathology Burden: This aim seeks to establish a relationship between the MPI signals generated by labeled MCT cells and the subsequent burden of pathological α-synuclein in the brain, a hallmark of LBD. This correlation could offer a predictive measure of therapeutic effectiveness and survival outcomes in treated animals. The proposed work aligns with the goals of the Administrative Supplement to Help Develop Alzheimer's Focused NIH Grants (NOT-AG-23-032) by contributing to the development of non-invasive techniques to advance our understanding of T cell-based therapies for neurodegenerative diseases. Achieving the proposed aims will establish MPI as a robust tool for non-invasively tracking therapeutic cells in the central nervous system, thereby facilitating the development and optimization of ACT therapies in the context of LBD and potentially other α- synucleinopathies.