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

• Published in: Frontiers in oncology Vol. 11; p. 730358
• Main Authors: Miner, Maxwell W. G., Liljenbäck, Heidi, Virta, Jenni, Helin, Semi, Eskola, Olli, Elo, Petri, Teuho, Jarmo, Seppälä, Kerttu, Oikonen, Vesa, Yang, Guangli, Kindler-Röhrborn, Andrea, Minn, Heikki, Li, Xiang-Guo, Roivainen, Anne
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.10.2021
• Subjects: FDG; fluoroglutamine; glioma; methionine; modeling; Oncology; rat; fluoroglutamine; modeling; rat; methionine; FDG; glioma; positron emission tomography; PET
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.730358

The three positron emission tomography (PET) imaging compounds: (2 ,4 )-4-[ F]Fluoroglutamine ([ F]FGln), -[methyl- C]Methionine ([ C]Met), and 2-deoxy-2-[ F]fluoro- -glucose ([ F]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 [ F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison. 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 [ C]Met, 60 min [ F]FDG, and 60 min [ F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). brain autoradiography was completed for each radiopharmaceutical and [ F]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 [ F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models. Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [ F]FGln TBR: 1.99 ± 0.19 (n = 13), [ F]FDG TBR: 1.41 ± 0.11 (n = 6), and [ C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [ F]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). In orthotopic BT4C gliomas, [ F]FGln may offer improved imaging [ C]Met and [ F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [ F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.