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IntroductionNon-invasive imaging techniques such as positron emission tomography (PET) are extremely important for cancer detection and characterization especially for difficult to biopsy or extremely delicate organs such as the brain. The folate analogue 1,4,7-triazacylononane-1,4,7-triacetic acid-conjugated folate radiolabeled with aluminum fluoride-18 ([18F]FOL) has been previously shown to accumulate preferentially in tumor cells with an overexpression of folate receptors (FRs) and here was investigated for its ability to detect orthotopic gliomas in a rat model. In addition, we studied the expression of FRs in human glioblastoma samples to investigate if an analogous relationship may exist.MethodsNine BDIX rats were injected with BT4C rat glioma cells into the right hemisphere of the brain. Animals were imaged with gadolinium-enhanced magnetic resonance imaging at on days prior to PET/computed tomography (CT) imaging. Animals were divided into two groups, and were PET/CT imaged with either [18F]FOL or 2-deoxy-2-18F-fluoro-D-glucose ([18F]FDG) on 19 and 32-days post glioma grafting. Two subjects were also PET/CT imaged with [18F]FOL on day 16. Biodistribution was studied and brains were cryosectioned for autoradiography, immunofluorescence, and histological studies. Patient-derived paraffin-embedded glioblastomas were sectioned and stained with similar methods.ResultsPET imaging showed an increase of [18F]FOL tumor-to-brain uptake ratio (TBR) over the study duration from day 16/19 (3.3 ± 0.9) increasing to 5.7 ± 1.0 by day 32. [18F]FDG PET-imaged rats had a consistent TBR of 1.6 ± 0.1 throughout the study. Ex vivo autoradiography results revealed an exceptionally high TBR of 116.1 ± 26.9 for [18F]FOL while the [18F]FDG values were significantly lower giving 2.9 ± 0.6 (P

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.

Myocardial perfusion imaging (MPI) with positron emission tomography (PET) allows quantitative temporal measurements of the radioactive tracer distribution in tissue. The quantification for myocardial blood flow (MBF) is conducted with kinetic modeling of the image-derived time-activity curves (TACs) allowing derivation for MBF in units of mL/min per gram of tissue. The ordered-subset expectation maximization (OSEM) reconstruction algorithm with time-of-flight (TOF) and point spread function (PSF) modeling is now routinely employed in cardiac imaging. However, the varying counting statistics of the MPI measurements conducted with short-lived tracers present a challenge for the PET image reconstruction methods. Thus, the effect of the reconstruction methods on the flow quantification needs to be evaluated in a standardized manner. Recently, a novel PET flow phantom modeling the MBF has been developed for investigation of the standardization of the MBF measurements. In this study, the effect of the reconstruction parameters on the image-derived flow values against a known reference flow of the flow phantom was studied with [15O]H2O. The effects were studied by comparison of TACs and relative errors of the image-derived flow values with respect to the phantom-derived reference flow value using 5 repeated PET scans with fixed acquisition parameters using a digital Discovery MI PET/CT system. The reconstruction methods applied were OSEM using both TOF and PSF (OSEM-TOF-PSF) with several matrix sizes (128 x 128, 192 x 192, 256 x 256, 384 x 384), Gaussian filter sizes (4, 8 mm) and OSEM without TOF and PSF (OSEM), with TOF (OSEM-TOF) and with PSF (OSEM-PSF) in addition to recently introduced regularized reconstruction method based on Bayesian-penalized maximum likelihood (Q.Clear). Between repeated measurements, the image-derived flow values showed high repeatability with a SD less than 2 mL/min as well as high accuracy with the maximum error of 7% with respect to the reference flow for all reconstructions. Overall, reconstruction settings had only a small impact on the resulting flow values. In conclusion, due to the small differences detected, any of the implemented reconstruction algorithms on the system can be applied in MPI studies for accurate flow quantification.

In this review, we will summarize the past and current state-of-the-art developments in attenuation and scatter correction approaches for hybrid positron emission tomography (PET) and magnetic resonance (MR) imaging. The current status of the methodological advances for producing accurate attenuation and scatter corrections on PET/MR systems are described, in addition to emerging clinical and research applications. Future prospects and potential applications that benefit from accurate data corrections to improve the quantitative accuracy and clinical applicability of PET/MR are also discussed. Novel clinical and research applications where improved attenuation and scatter correction methods are beneficial are highlighted.