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Background A critical need in adoptive T cell therapy is the ability to noninvasively and longitudinally track engineered T cells in vivo, as biodistribution and persistence directly impact efficacy and safety. We previously developed a novel theranostic platform by engineering CD19 CAR-T cells to express a membrane-bound scFv, huC825, which binds DOTA-haptens with picomolar affinity, rendering it suitable for labeling with diagnostic or therapeutic radionuclides. Here, we applied this platform to newly developed anti-IL13Rα2-scFv-derived CAR-T cells (KLG3BBz-huC825) and evaluated their biodistribution and persistence in a human melanoma xenograft model using immunoPET.Methods Second-generation IL13Rα2-targeted CAR-T cells co-expressing huC825 were engineered and validated for antigen-specific cytotoxicity and cytokine production in vitro. We evaluated in vivo detection sensitivity using a T cell titration assay. Furthermore, NSG mice were engrafted with A375 melanoma tumors and seven days later intravenously (IV) injected with KLG3BBz-huC825 or non-transduced (NT) T cells. We performed weekly [ 8 6Y]Y-ABD-based whole-body PET/CT and monitored the outcome.Results KLG3BBz-huC825 CAR-T cells exhibited potent antigen-specific cytotoxicity and cytokine production in vitro. ImmunoPET visualized uptake at the tumor site already on day 7 post T cell infusion (4.67 ± 1.76 %ID/g; n=4), peaking at day 14 (16 ± 7.67 %ID/g, n=3), with persistence up to day 49 (3.51%ID/g, n=1) in mice injected with KLG3BBz-huC825 CAR-T cells. Uptake in normal organs and tumor site correlated with T cell infiltration on histologic assessment. In contrast, minimal uptake at the tumor site and normal tissues was seen in control mice receiving NT T cells. Mice treated with KLG3BBz-huC825 showed significantly prolonged survival compared to mice treated with NT (median 44.5 vs. 20 days).Conclusions This immunoPET-enabled tracking platform offers exquisite sensitivity and spatiotemporal resolution to monitor CAR-T cell dynamics in vivo. It provides a clinically translatable strategy to guide next-generation CAR-T cell therapy through improved understanding of trafficking, persistence, and tumor engagement. Such approaches could support early therapeutic monitoring, adaptive dosing, and stratification in clinical immunotherapy trials.