Abstract
PurposeThe 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.ProceduresUp 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.ResultsAverage 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).ConclusionsIn 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.
Highlights
With an increasing number techniques and compounds available in neuro-oncology, it becomes important to contrast and compare their abilities to image and diagnose the tumors
In this article we present our continued success in synthesizing [18F]FGln and our comparative in vivo Positron emission tomography (PET) imaging evaluation thereof juxtaposed with the well-established radiopharmaceuticals [18F]FDG and [11C]Met to image BDIX rats bearing BT4C gliomas
Subjects were injected with BT4C rat glioma cells (10,000 cells in 5 μL of plain growth medium) into the right hemisphere of the brain after drilling a small hole in the skull
Summary
With an increasing number techniques and compounds available in neuro-oncology, it becomes important to contrast and compare their abilities to image and diagnose the tumors. Radionuclide-labelled amino acids and amino-acid analogues are radiopharmaceuticals of choice in the PET imaging of gliomas because of their low uptake in normal brain tissue These compounds are generally well transported throughout the body due to biochemical ubiquity and can have an increased uptake in metabolically-active or dividing tissues such as tumors [3]. Methionine in humans is an essential amino acid, which needs to be ingested from external sources and transported throughout the body It is the amino acid encoded by the start codon for most proteins and its use and subsequent cellular pool depletion is tied heavily to the commencement of protein synthesis. Methionine cellular pool depletion and subsequent increased [11C]Met cellular uptake rates by cancer cells can be inherently variable depending on mutational status
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