Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

Abstract

BackgroundDiscrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.MethodsDynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed.ResultsThe influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN.ConclusionsBased on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

Feasibility and robustness of dynamic 18F-FET PET based tracer kinetic models applied to patients with recurrent high-grade glioma prior to carbon ion irradiation

“…Overall, the standard 1TCM provided the best results in terms of feasibility and robustness with an appropriate description of the tracer kinetics. This is in concordance with results reported in animal studies 24 . Additionally, correlation of K 1 with overall patient survival was visible in K 1 from both the 1TCM and 2TCM.…”

“…There are only few reports on detailed compartment model analysis in 18 F-FET PET in patients, and the question, which model best describes the kinetics of tracer uptake, metabolism and washout is still unanswered 23 , 24 . However, voxelwise tracer kinetic analysis holds the promise of unraveling tumor sub-volumes of different metabolic activity, which is especially relevant in high-grade glioma due to their infiltrative and heterogeneous nature.…”

“…However, most of them resort to either qualitative analysis of curve shapes or derivation of semi-quantitative parameters such as the initial slope or time to peak. Few authors applied detailed pharmacokinetic analysis using different compartment models 23 , 24 , but parameter robustness and reliability were not investigated.…”

Editorial commentary to “18F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases” by Grkovski and colleagues

“…More importantly and thanks to collaboration with neurosurgeons, authors pointed out a significant correlation between 18 F-FCH uptake and not only the percentage of viable tumor but also inflammation and reactive gliosis quantified by the pathologist. Radiolabeled choline uptake in inflammation was previously reported [8,9], demonstrated in rat models [10,11] and might be responsible for a limited specificity of 18 F-FCH to differentiate viable tumor from post-radiation processes, including radionecrosis [12,13]. In this study, quantification of 18 F-FCH uptake revealed higher tracer uptake in the presence of tumor than in the absence of tumor, though with SUV overlap.…”

Dual-tracer simultaneous acquisition of positron emission tomography

“…The specific injected activities for each cassette are shown in Table 5-1, with activities from each container normalised for differing injection doses. to acquired single-tracer data (used in previous experiment) and the literature (130,131) for manually delineated ROIs of brain tumour and cortical tissue. While only a single mouse was imaged, the large number of intra-subject voxels allows voxel-wise investigations to be performed.…”