Purpose: The glutamine analogue (2S, 4R)-4-[18F]fluoroglutamine ([18F]FGln) was investigated to

further characterize its pharmacokinetics and acquire in vivo positron emission tomography (PET)

images of separate orthotopic and subcutaneous glioma xenografts in mice.

Procedures: [18F]FGln was synthesized at a high radiochemical purity as analyzed by high-performance

liquid chromatography. An orthotopic model was created by injecting luciferase-expressing

patient-derived BT3 glioma cells into the right hemisphere of BALB/cOlaHsd-Foxn1nu mouse

brains (tumor growth monitored via in vivo bioluminescence), the subcutaneous model by injecting rat

BT4C glioma cells into the flank and neck regions of Foxn1nu/nu mice. Dynamic PET images were

acquired after injecting 10–12 MBq of the tracer into mouse tail veins. Animals were sacrificed 63 min

after tracer injection, and ex vivo biodistributions were measured. Tumors and whole brains (with tumors)

were cryosectioned, autoradiographed, and stained with hematoxylin-eosin. All images were analyzed

with CARIMAS software. Blood sampling of 6 Foxn1nu/nu and 6 C57BL/6J mice was performed after 9–

14 MBq of tracer was injected at time points between 5 and 60 min then assayed for erythrocyte uptake,

plasma protein binding, and plasma parent-fraction of radioactivity to correct PET image-derived whole-blood

radioactivity and apply the data to multiple pharmacokinetic models.

Results: Orthotopic human glioma xenografts displayed PET image tumor-to-healthy brain region ratio

of 3.6 and 4.8 while subcutaneously xenografted BT4C gliomas displayed (n = 12) a tumor-to-muscle

(flank) ratio of 1.9 ± 0.7 (range 1.3–3.4). Using PET image-derived blood radioactivity corrected by

population-based stability analyses, tumor uptake pharmacokinetics fit Logan and Yokoi modeling for

reversible uptake.

Conclusions: The results reinforce that [18F]FGln has preferential uptake in glioma tissue versus

that of corresponding healthy tissue and fits well with reversible uptake models.