C57BL/6,
ITK-SYKCD4-CreERT2 or
ITK-SYKCD4-CreERT2;
Pdcd1−/− mice received a single dose of 2 mg tamoxifen. For PET–CT imaging, mice were injected with [
18F]FDG (~12 MBq), and tracer uptake was measured after 90 min using a preclinical Siemens
Inveon PET–CT system. Splenic standardized uptake values were calculated using Inveon Research Workplace software. Hyperpolarized
13C MRI of the animals was performed using a preclinical 7-T magnetic resonance scanner (Agilent–GE Discovery MR901 magnet and gradient system, Bruker
AVANCE III HD electronics). The animals were injected with hyperpolarized [1-
13C]pyruvate (250 µl, 80 mM,
HyperSense DNP, Oxford Instruments), and both [1-
13C]pyruvate and [1-
13C]lactate were recorded in vivo using a static 2D FID–CSI (matrix size, 18 × 12; FOV, 30 mm × 20 mm; slice thickness, 3 mm; flip angle, 12°; number of points, 128; bandwidth, 2,000 Hz).
T2-weighted images (
1H-RARE; matrix size, 150 × 100; FOV, 30 mm × 20 mm; slice thickness, 1 mm) were recorded for co-registration and determination of spleen size. Peak heights for [1-
13C]pyruvate versus [1-
13C]lactate were determined and summed over the spleen region of interest using MATLAB code developed in house.
Wartewig T., Daniels J., Schulz M., Hameister E., Joshi A., Park J., Morrish E., Venkatasubramani A.V., Cernilogar F.M., van Heijster F.H., Hundshammer C., Schneider H., Konstantinidis F., Gabler J.V., Klement C., Kurniawan H., Law C., Lee Y., Choi S., Guitart J., Forne I., Giustinani J., Müschen M., Jain S., Weinstock D.M., Rad R., Ortonne N., Schilling F., Schotta G., Imhof A., Brenner D., Choi J, & Ruland J. (2023). PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. Nature Cancer, 4(10), 1508-1525.