In Vivo Tracking of Th1 Cells by PET Reveals Quantitative and Temporal Distribution and Specific Homing in Lymphatic Tissue

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. Methods: We developed protocols that minimize the inhibitory effects of 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-PTSM) la-beling 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)-g–producing CD41 T (Th1) cells with 0.7–2.2 MBq of 64Cu-PTSM and analyzed cell viability, IFN-g production, proliferation, apoptosis, and DNA double-strand breaks and identified intracellular 64Cu accumulation sites by energy dis-persive x-ray analysis. To elucidate the fate of Th1 cell homing by PET, 107 64Cu-OVA-Th1 cells were injected intraperitoneally or in-travenously into healthy mice. To test the functional capacities o