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• W2132401119 abstract "Although T cells can be labeled for noninvasive in vivo imaging, little is known about the impact of such labeling on T-cell function, and most imaging methods do not provide holistic information about trafficking kinetics, homing sites, or quantification. <b>Methods:</b> We developed protocols that minimize the inhibitory effects of ⁶⁴Cu-pyruvaldehyde-bis(<i>N</i>4-methylthiosemicarbazone) (⁶⁴Cu-PTSM) labeling on T-cell function and permit the homing patterns of T cells to be followed by PET. Thus, we labeled ovalbumin (OVA) T-cell receptor transgenic interferon (IFN)-γ–producing CD4⁺ T (Th1) cells with 0.7–2.2 MBq of ⁶⁴Cu-PTSM and analyzed cell viability, IFN-γ production, proliferation, apoptosis, and DNA double-strand breaks and identified intracellular ⁶⁴Cu accumulation sites by energy dispersive x-ray analysis. To elucidate the fate of Th1 cell homing by PET, 10^{7 64}Cu-OVA-Th1 cells were injected intraperitoneally or intravenously into healthy mice. To test the functional capacities of ⁶⁴Cu-OVA-Th1 cells during experimental OVA-induced airway hyperreactivity, we injected 10^{7 64}Cu-OVA-Th1 cells intraperitoneally into OVA-immunized or nonimmunized healthy mice, which were challenged with OVA peptide or phosphate-buffered saline or remained untreated. In vivo PET investigations were followed by biodistribution, autoradiography, and fluorescence-activated cell sorting analysis. <b>Results:</b> PET revealed unexpected homing patterns depending on the mode of T-cell administration. Within 20 min after intraperitoneal administration, ⁶⁴Cu-OVA-Th1 cells homed to the perithymic lymph nodes (LNs) of naive mice. Interestingly, intravenously administered ⁶⁴Cu-OVA-Th1 cells homed predominantly into the lung and spleen but not into the perithymic LNs. The accumulation of ⁶⁴Cu-OVA-Th1 cells in the pulmonary LNs (6.8 ± 1.1 percentage injected dose per cubic centimeter [%ID/cm³]) 24 h after injection was highest in the OVA-immunized and OVA-challenged OVA airway hyperreactivity–diseased littermates 24 h after intraperitoneal administration and lowest in the untreated littermates (3.7 ± 0.4 %ID/cm³). As expected, ⁶⁴Cu-OVA-Th1 cells also accumulated significantly in the pulmonary LNs of nonimmunized OVA-challenged animals (6.1 ± 0.5 %ID/cm³) when compared with phosphate-buffered saline–challenged animals (4.6 ± 0.5 %ID/cm³). <b>Conclusion:</b> Our protocol permits the detection of Th1 cells in single LNs and enables temporal in vivo monitoring of T-cell homing over 48 h. This work enables future applications for ⁶⁴Cu-PTSM–labeled T cells in clinical trials and novel therapy concepts focusing on T-cell–based immunotherapies of autoimmune diseases or cancer." @default.
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• W2132401119 date "2014-01-16" @default.
• W2132401119 modified "2023-10-13" @default.
• W2132401119 title "In Vivo Tracking of Th1 Cells by PET Reveals Quantitative and Temporal Distribution and Specific Homing in Lymphatic Tissue" @default.
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• W2132401119 doi "https://doi.org/10.2967/jnumed.113.126318" @default.
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