Background and Purpose:
Glioblastomas are the most aggressive of all gliomas. The prognosis of these gliomas, which are classified as grade IV tumors by the World Health Organization (WHO), is poor. Combination therapy, including surgery, radiotherapy, and chemotherapy has variable outcomes and is expensive. In light of rising healthcare costs, there are societal demands for the justification of medical expenses. Therefore, we calculated the cost-effectiveness of follow-up [
18
F] fluoroethyl-L-tyrosine ([
18
F] FET) positron emission tomography (PET) scans performed on patients with glioblastoma after surgery and before commencing temozolomide maintenance treatment.
Materials and Methods:
To determine the cost-effectiveness of follow-up [
18
F] FET PET procedures, we examined published clinical data and calculated the associated costs in the context of Belgian healthcare. We subsequently performed one-way deterministic sensitivity analysis and Monte Carlo analysis on the calculated ratios.
Results:
The decision tree based on overall survival rates showed that the number of non-responders identified using PET was 57.14% higher than the number of non-responders identified using conventional MRI. Further, the decision tree based on progression-free survival rates revealed a comparable increase of 57.50% non-responders identified. The calculated cost of two required PET scans per patient during the follow-up treatment phase was 780.50 euros. Two cost-effectiveness ratios were determined for overall survival and progression-free survival rates. Both of these calculations yielded very similar results: incremental cost-effectiveness ratios of 1,365.86 and 1,357.38 euros, respectively, for each identified non-responder. The findings of the sensitivity analysis supported the calculated results, confirming that the obtained data were robust.
Conclusion:
Our comparative study of conventional MRI and [
18
F] FET PET revealed that the latter is a valuable tool for predicting the treatment responses of patients with glioblastomas to follow-up temozolomide maintenance treatment while considering its cost-effectiveness. Thus, [
18
F] FET PET scans enable clinical outcomes to be predicted accurately and at a low cost. Moreover, given the robustness of the data in the sensitivity analyses, the level of certainty of this outcome is acceptable.
AbstractIntroductionGlucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors. We elaborated on the glutamine-derived PET tracers by developing two novel probes, namely [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamineMaterials and methodsBoth tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [3H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model.ResultsThe radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18 % (n=10) ([18F]fluorophenylglutamine) and 8.05 ± 3.25 % (n=5) ([18F]fluorobiphenylglutamine). In vitro inhibition experiments showed a moderate and low affinity of fluorophenylglutamine and fluorobiphenylglutamine, respectively, towards the human ASCT-2 transporter. Both compounds had a low affinity towards the rat ASCT-2 transporter. These results were endorsed by the in vivo experiments with low uptake of both tracers in the F98 rat xenograft, low uptake of [18F]FBPG in the mice PC-3 xenograft and a moderate uptake of [18F]FPG in the PC-3 tumors.ConclusionWe investigated the imaging potential of two novel PET radiotracers [18F]FPG and [18F]FBPG. [18F]FPG is the first example of a glutamine radiotracer derivatized with a phenyl group which enables the exploration of further derivatization of the phenyl group to increase the affinity and imaging qualities. We hypothesize that increasing the affinity of [18F]FPG by optimizing the substituents of the arene ring can result in a high-quality glutamine-based PET radiotracer.Advances in Knowledge and Implications for patient careWe hereby report novel glutamine-based PET-tracers. These tracers are tagged on the arene group with fluorine-18, hereby preventing in vivo defluorination, which can occur with alkyl labelled tracers (e.g. (2S,4R)4-[18F]fluoroglutamine). [18F]FPG shows clear tumor uptake in vivo, has no in vivo defluorination and has a straightforward production. We believe this tracer is a good starting point for the development of a high-quality tracer which is useful for the clinical visualization of the glutamine transport.
Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [ 18 F]fluorophenylglutamine and [ 18 F]fluorobiphenylglutamine.
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