Comparison of: (2S,4R)-4-[¹⁸F]Fluoroglutamine, [¹¹C]Methionine, and 2-Deoxy-2-[¹⁸F]Fluoro-D-Glucose and Two Small-Animal PET/CT Systems Imaging Rat Gliomas

Purpose: The three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[¹⁸F]Fluoroglutamine ([¹⁸F]FGln), L-[methyl-¹¹C]Methionine ([¹¹C]Met), and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [¹⁸F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison. Procedures: Up to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [¹¹C]Met, 60 min [¹⁸F]FDG, and 60 min [¹⁸F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [¹⁸F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [¹⁸F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models. Results: Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [¹⁸F]FGln TBR: 1.99 ± 0.19 (n = 13), [¹⁸F]FDG TBR: 1.41 ± 0.11 (n = 6), and [¹¹C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [¹⁸F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25). Conclusions: In orthotopic BT4C gliomas, [¹⁸F]FGln may offer improved imaging versus [¹¹C]Met and [¹⁸F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [¹⁸F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics. CA extern