Access the full text.
Sign up today, get DeepDyve free for 14 days.
References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.
REVIEW ARTICLE Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know N. Soni, M. Ora, A. Jena, P. Rana, R. Mangla, S. Ellika, J. Almast, S. Puri, and S.P. Meyers ABSTRACT SUMMARY: PET with amino acid tracers provides additional insight beyond MR imaging into the biology of gliomas that can be used for initial diagnosis, delineation of tumor margins, planning of surgical and radiation therapy, assessment of residual tumor, and evaluation of posttreatment response. Hybrid PET MR imaging allows the simultaneous acquisition of various PET and MR imag- ing parameters in a single investigation with reduced scanning time and improved anatomic localization. This review aimed to pro- vide neuroradiologists with a concise overview of the various amino acid tracers and a practical understanding of the clinical applications of amino acid PET MR imaging in glioma management. Future perspectives in newer advances, novel radiotracers, radiomics, and cost-effectiveness are also outlined. ABBREVIATIONS: AAT ¼ amino acid tracer; AA ¼ amino acid; ASCT ¼ alanine-serine-cysteine transporter; BTV ¼ biologic tumor volume; GBM ¼ glioblas- 18 18 toma multiforme; FDOPA ¼ 3,4-dihydroxy-6-[ F]ﬂuoro-L-phenylalanine; FET ¼ O-(2-[ F]ﬂuoroethyl)-L-tyrosine; LAT ¼ large amino acid transporter; HGG ¼ high-grade glioma; LGG ¼ low-grade glioma; MET ¼ C-methionine; rCBV ¼ relative CBV; TAC ¼ time-activity curve; TBR ¼ tumor-to-background ratio; TRC ¼ treatment-related changes; TSPO ¼ translocator protein; WHO ¼ World Health Organization liomas represent approximately 80% of malignant brain Advanced MR imaging techniques such as PWI, DWI, DTI, Gtumors, with an annual incidence rate of 5.6 cases per MRS, and molecular imaging (PET) facilitate visualization and 100,000 individuals worldwide. Glioblastoma multiforme (GBM) quantification of different metabolic processes and improve over- is the most common primary malignant brain tumor, representing all diagnostic performance in brain tumors. Hybrid PET MR approximately 50% of all gliomas and 16% of all brain tumors. imaging with novel radiotracers provides a noninvasive, simulta- Depending on the size and extent of these tumors, the standard of neous assessment of brain tumor morphologic, functional, meta- 3,4 care for newly diagnosed GBMs usually includes maximal surgical bolic, and molecular parameters. resection followed by radiation and chemotherapy. Despite sub- This review aimed to provide neuroradiologists with a concise stantial development in managing high-grade gliomas (HGGs), overview of the various amino acid tracers (AATs) and a practical the median survival is ,15 months, with 1- and 5-year survival understanding of the clinical applications of amino acid (AA) rates of 40% and 5.5%, respectively. PET MR imaging in glioma management. We will review the cur- Imaging is crucial for diagnosing, guiding biopsy, surgical rent literature regarding AA-PET MR imaging in glioma treat- planning, and distinguishing treatment-related changes (TRC) ment and discuss its role in the initial diagnosis, delineation of from recurrence in glioma management. MR imaging is the pri- tumor margin, planning of radiation therapy, assessment of resid- mary imaging technique; however, it lacks specificity to distin- ual tumor, and evaluation of treatment response. We will sum up guish between viable neoplastic tissue and tumor-free areas. with future perspectives on newer advances, novel radiotracers, radiomics, and cost-effectiveness. Received October 13, 2022; accepted after revision November 21. From the University of Rochester Medical Center (N.S., S.E., J.A., S.P., S.P.M.), Radiopharmaceuticals Rochester, New York; Sanjay Gandhi Postgraduate Institute of Medical Sciences (M.O.), Lucknow, Uttar Pradesh, India; Indraprastha Apollo Hospital The Joint European Association of Nuclear Medicine (EANM)/ (A.J., P.R.), New Delhi, India; and Upstate University Hospital (R.M.), Syracuse, European Association of Neuro-Oncology (EANO)/Response New York. Assessment in Neuro-Oncology (RANO)/Society of Nuclear Neetu Soni and Manish Ora are ﬁrst authors. Medicine and Molecular Imaging (SNMMI) guidelines provide Please address correspondence to Neetu Soni, MD, DNB, FRCR, 601 Elmwood Ave, Rochester, NY 14612; e-mail: firstname.lastname@example.org; @NeetuSo27437480 the performance, interpretation of molecular imaging, and clini- Indicates open access to non-subscribers at www.ajnr.org cal application of several PET radiotracers (Online Supplemental Data), including imaging of glucose metabolism FDG and the Indicates article with online supplemental data. http://dx.doi.org/10.3174/ajnr.A7762 L-amino acid transport system C-methionine (MET), O-(2- 236 Soni Mar 2023 www.ajnr.org FIG 1. Simultaneous AAT-PET MR imaging acquisition protocol. Min indicates minute; UTE, ultrashort echo time; vol, volume; SUV, standardized uptake value. 18 18 [ F]fluoroethyl)-L-tyrosine (FET), and 3,4-dihydroxy-6-[ F]flu- ASCT2 transporters are overexpressed in gliomas more than in oro-L-phenylalanine (FDOPA). normal brain cells, resulting in high TBR. FDOPA exhibits physi- ologic uptake in the basal ganglia, which underestimates basal Why Are AATs Supplanting FDG? The radiotracer most compre- ganglia region malignancies. hensively explored and evaluated for oncology is FDG. Tumors overexpress GLUT1 with enhanced hexokinase phosphorylation, Hybrid PET MR Imaging Acquisition Protocol resulting in increased FDG uptake. FDG has physiologic uptake in Two types of hybrid PET MR imaging scanners are sequential the brain parenchyma, resulting in a poor tumor-to-background and integrated. A sequential system uses a single bed for both ratio (TBR). A recent review showed higher sensitivity of AATs MR imaging and PET scans, which lessens misregistration. An than FDG in differentiating tumor progression and TRC in integrated system simultaneously acquires PET and MR imaging HGGs. FDG (12 studies, 171 lesions), FET (7 studies, 172 lesions), data. Brain AAT-PET MR imaging is performed immediately and MET (8 studies, 151 lesions) showed a pooled sensitivity of after tracer injection for 20–25 minutes, during which the 84%, 90%, 93% and specificity of 84%, 85%, 82%, respectively. In advanced MR imaging sequences are performed with continu- 3 18 a meta-analysis (33 studies, 1734 patients), FET-PET has shown a ous PET acquisition (Fig 1). Dynamic [ F] FET-PET imaging higher sensitivity (0.88) and lower specificity (0.78) than FDG studies the temporal distribution of tracers within the tumor PET (sensitivity, 0.78; specificity, 0.87) for glioma recurrence. and healthy brain. It generates the time-activity curves (TACs) MET and FDOPA-PET also offer good sensitivity (0.92 and 0.85) to characterize the pattern of FET kinetics in gliomas. Among with moderate specificity (0.78 and 0.70). Despite the drawbacks, the various AATs, FET has an established added clinical value 3 3 FDG is commonly used due to the limited availability of AATs. for dynamic acquisition. HGGs may be distinguished from low- FDG is a ubiquitous PET tracer and the most widely used tracer grade gliomas (LGGs) on the basis of their early time-to-peak in oncology. It has a long half-life (110 minutes) and is easily (0–20 minutes) and the late-phase analysis (20–40 minutes) of 11-13 transportable to a distant lab if the center does not have an onsite plateaued or declining uptake. A steady increase in uptake up cyclotron. At the same time, the C-labeled tracer has a short to 40 minutes after the injection suggests grade I and II gliomas half-life (20 minutes 4 seconds), which limits the remote transport and TRC. and scheduling of multiple patients. Clinical Indications for PET MR Imaging in Glioma What Are Amino Acids, and What Are Their Functions? Management AAs are the building blocks of proteins, including enzymes, hor- Recommendations from the Joint EANM/EANO/RANO/SNMMI mones, membrane channels, and transporters. They are essential guidelines for using AATs in clinical imaging fall into 4 categories: for growth regulation, signaling pathways, and energy produc- 1) diagnosis and grading, 2) noninvasive tumor genotyping, 3) tion. There are 2 main groups of AA transporters: the large tumor margin delineation for radiation therapy planning, and 4) amino acid transporter (LAT) and Na1-independent transport- disease and treatment monitoring. These are discussed in more ers (alanine-serine-cysteine transporter [ASCT]). The active in- detail in the following sections. tracellular absorption of radiolabeled AATs by the LAT and Initial Diagnosis, Sampling, and Grading. It is crucial to distin- ASCT is the basis for AAT-PET. L-DOPA, L-tyrosine, and methi- guish benign from malignant brain lesions to avoid invasive onine are specific substrates for the LAT1. FET and [ F] fluciclo- biopsy (Fig 2). The high specificity and negative predictive value vine resemble their corresponding AAs, tyrosine and L-leucine. of FET-PET MR imaging help to rule out malignancy with an ac- Why AATs Are an Excellent Choice for Glioma Metabolism curacy of 85% and a change in management in 33% of the Imaging. HGGs show a strong correlation between the uptake of untreated equivocal lesions. FET-PET offers supplemental in- 8,9 MET and FDOPA with elevated LAT1 expression. LAT1 and formation on tumor extent and biopsy target selection compared AJNR Am J Neuroradiol 44:236–46 Mar 2023 www.ajnr.org 237 FIG 2. A 12-year-old boy presented with right focal seizures for a month. Electroencephalography was noncontributory. Imaging-based di- agnosis of a tuberculoma was made on the initial contrast-enhanced MR imaging in November 2019. Antitubercular treatment was started empirically. Follow-up MR imaging in February 2022 showed an interval increase of the mass from approximately 1.5 1.3 cm to 3.8 3.6 cm (images not shown), which led to further work-up, and the patient underwent AA-PET MR imaging and FDOPA-PET MR imag- ing. T2 FLAIR (A) demonstrates a hyperintense left posterior frontal mass with equivocal diffusion restriction on the diffusion-weighted image (B and C, blue arrow). A predominantly nonenhancing mass with small peripheral nodular enhancement is seen on postcontrast T1- weighted image (D, blue arrow). No apparent increased regional CBV is seen on DSC PWI (E, white arrow). On FDOPA-PET (F, blue arrow) and fused FDOPA-PET MR imaging (G, white arrow), the lesion showed uniformly increased DOPA uptake throughout with a high maxi- mum standard uptake value of 3.62 (lesion/striatum ratio of 1.81 versus ,1.0 as normal) and TBR. Multivoxel MRS (H) showed Cho/NAA and Cho/Cr ratios of 2.78 and 1.4, respectively, with a prominent lactate peak. In this patient, FDOPA-PET MR imaging conﬁrmed the pre- cise diagnosis of neoplastic etiology, which, on biopsy, was revealed to be an anaplastic astrocytoma. CE indicates contrast-enhanced. 238 Soni Mar 2023 www.ajnr.org FIG 3. A 43-year-old man treated for a left anterior temporal lobe glioblastoma (IDH wild-type) status post resection (positive for generalized paroxysmal fast activity, negative for p53 and IDH1, MIB1 labeling index ¼ 10%–12%, ﬂuorescence in site hybridization epidermal growth factor re- ceptor ampliﬁcation, and no loss of 1p19q) and chemoradiation. He underwent follow-up FET-PET MR imaging after 3 years. T2 FLAIR (A, blue arrow) image shows postsurgical changes in the left anterior temporal lobe with peripheral nodular enhancement on the postcontrast T1- weighted image (B), mild increased diffusion restriction (C), and increased perfusion (rCBV of 6.7). Multivoxel MRS (E) shows noisy spectra with mildly raised choline and an inverted lactate peak. Corresponding increased FET uptake (TBR ¼ 2.8; maximum standard uptake value ¼ 3.7) on FET-PET (F) and fused FET-PET MR imaging (G, white arrow). The patient underwent resection, and pathology showed a recurrent tumor. This case highlights the congruent ﬁndings on contrast-enhanced MR imaging and FET-PET with a larger TBR leading to less interobserver variability and improving diagnostic performance for differentiating recurrence from TRC. CE indicates contrast-enhanced. with MR imaging, which further improves with dynamic PET. discriminate LGGs from HGGs were similar, with an area under Dual time-point FET-PET-based targeted biopsies from non- the curve TBR maximum of FET-PET uptake and rCBV being contrast-enhanced areas have shown that FET uptake corre- 0.83 and 0.81, respectively. Similar trends were observed with 15 20 sponded to HGGs as far as 3 cm from contrast enhancement. combined FDOPA-PET and multiparametric MR imaging. FET-PET-based TBR and PWI-determined relative CBV Noninvasive Tumor Genetic Profile and Molecular Markers. (rCBV) provide congruent and complementary information on Gliomas with IDH1 mutations have better chemoradiation glioma biology, with a moderate overlap of the tumor vol- responses and longer survival. AAT-PET MR imaging has the umes. FET-PET may improve the outcome of surgical plan- potential to serve as an alternative to invasive tissue characteriza- ning in both newly diagnosed and recurrent tumors (Fig 3). tion. In 52 patients with gliomas, FET-PET with PWI differenti- AAT-PET biologic tumor volume (BTV) often differs from con- ated 1p/19q codeletion oligodendrogliomas with IDH mutations trast-enhanced MR imaging BTV (Fig 4). Patients with residual from IDH wild-type glioblastomas. FDOPA-PET and MR FET uptake have worse outcomes than those with complete imaging metrics predicted the IDH mutation and 1p/19q codele- FET-PET BTV resection (median overall survival, 13.7 versus tion with sensitivities of 73% and 76% and specificities of 100% 19.3 months, P ¼ .007). The results were consistent regardless of and 94%, respectively. Oligodendrogliomas with the 1p/19q age, MGMT, IDH mutation, promoter, or adjuvant therapy codeletion had MET uptake as high as that of IDH wild-type glio- regimens. High- and low-grade subregions may coexist in gliomas. mas regardless of IDH1 mutation status. Therefore, MET-PET HGGs demonstrate higher uptake of AATs than LGGs. In a recent seems more useful for glioma grading in IDH wild-type glio- meta-analysis (7 studies, 219 patients), FDOPA-PET sensitivity mas. The FET-PET and the DWI-derived TBR/ADC ratio and specificity for glioma grading were 0.88 and 0.73, respec- showed higher diagnostic accuracy than the individual technique tively. The diagnostic accuracy of FET-PET and contrast PWI to for HGGs and IDH1, human telomerase reverse transcriptase, AJNR Am J Neuroradiol 44:236–46 Mar 2023 www.ajnr.org 239 FIG 4. A 35-year-old man was initially diagnosed with left frontal lobe oligodendroglioma grade II, status post resection and chemoradiation in 2008. He underwent a follow-up [ F] DOPA-PET MR imaging. T2 FLAIR axial (A) and coronal (B) images demonstrate a large cortical and subcorti- cal area of abnormal T2-FLAIR hyperintensity in the left parasagittal frontal lobe extending to the left gangliocapsular area and the corpus cal- losum and across the midline in the right parietal region without apparent diffusion restriction (C), enhancement (D), and increased rCBV perfusion (E). Multivoxel MRS (F) shows increased Cho/Cr and Cho/NAA ratios (1.86 and 2.31, respectively). FDG-PET MR imaging (G and H)shows no appreciable FDG uptake. FDOPA-PET MR imaging shows areas of signiﬁcant DOPA tracer uptake (maximum standard uptake value ¼ 1.54 ver- sus ,1.0 as normal) more prominently in the left paramedian frontal region. FDOPA-avid, FDG-nonavid nonenhancing lesion in the left frontal region involving the corpus callosum with positive MR imaging correlates suggests active underlying residual/recurrent disease. This case again highlights the superiority of AATs over FDG and the importance of multiparametric MR imaging over individual sequences. AAT uptake in the absence of contrast enhancement and increased perfusion helped with the planning of surgery and radiation. CE indicates contrast-enhanced. and epidermal growth factor receptor–mutated gliomas. Tumor codeletion and epidermal growth factor receptor mutations had regions with a human telomerase reverse transcriptase mutation lower ADC, and IDH1 mutations had higher TBR mean values. had higher TBR and lower ADC values, while tumor protein P53 FET-PET MR imaging predicted ATRX, MGMT, IDH1,and mutation showed lower TBR and higher ADC values. The 1p/19q 1p19q mutations in 85%, 76%, 89%, and 98%, respectively. 240 Soni Mar 2023 www.ajnr.org Tumor Margin Delineation and Defining Tumor Extent for cases of pseudoprogression within the first 12 weeks of therapy Radiation Therapy Planning. In radiation planning, accurate tu- and in cases of radionecrosis after 12 weeks of treatment. The mor delineation is essential to provide the maximum tumor dose recent RANO recommendation for AAT-PET also includes and minimize treatment-related damage to uninvolved regions. assessing the response to radiation in gliomas apart from target delineation, prognostication, and re-irradiation. MET-PET was Enhancing components on MR imaging are the usual target for moderately specific (74%) and highly sensitive (97%) in detecting target-volume definition, whereas a tumor may extend beyond recurrence. The sensitivity remained high (97%) and the speci- areas of enhancement. Conventional MR imaging inadequately 39,40 distinguishes edema, contrast-enhancing, non-contrast-enhanc- ficity rose to 93% when MET-PET MR imaging was used. A ing, and infiltrating tumors. PET hotspots represent high tumor large meta-analysis (33 studies, 1734 patients) evaluated FET, cell densities. In a recent biopsy-validated study, FET-PET MET, and FDOPA tracers for tumor recurrence with a sensitivity revealed precise glioma extent, allowing personalized treatment of 0.88, 0.92, and 0.85 and a specificity of 0.78, 0.78, and 0.70, respectively. The meta-analysis supports the incorporation of planning. FDOPA-PET–guided dose-escalated radiation ther- FET and MET in the treatment evaluation of HGGs. The amount apy significantly improved the overall survival in methylated and of literature on the efficacy of 3’-deoxy3’- F-fluorothymidine progression-free survival in unmethylated GBMs. In 30 patients 18 5 [ F-FLT] and FDOPA is insufficient for a conclusion. with HGGs, rCBV and the permeability (K2) map correlated with enhancing tumor volumes. FET-PET provided complemen- The FET-PET TBR and PWI-rCBV indicators performed tary information, suggesting that contrast-enhancing MR imag- moderately well in distinguishing progression from TRC in 104 ing underestimates the metabolically active tumor volume. patients (P ,.01). A criterion of rCBV maximum of .2.85 allowed a correct diagnosis of progression in 44 patients with a positive pre- Tumor volumes were larger in FET-PET than in rCBV maps dictive value of 100%. In the remaining 60 patients, progression and (P, .001), with low spatial similarity of both imaging parame- 30 31 TRC were discriminated in 78% of patients. FET-PET is of signifi- ters. Similar results by Lohmann et al demonstrated larger cant clinical importance in diagnosing pseudoprogression related to metabolically active tumor volume by FET-PET than by contrast chemoradiation. FET-PET performed a mean of 10 (SD, 7) days af- enhancement (P, .001) and lower spatial similarity. FET-PET resulted in a mean increase of 27% from clinical target volumes ter the equivocal MR imaging findings showed a high accuracy of to biologic tumor volumes. 87% to identify pseudoprogression, with an improved specificity of 100%. A combined analysis of arterial spin-labeled CBF and Immediate Postsurgical Residual Tumor Evaluation. The assess- FDOPA uptake allowed high diagnostic performance in differentiat- ment of the early postoperative resection status in HGGs is neces- ing progression and pseudoprogression in treated gliomas. Given sary for surgical re-evaluation in the large residual disease. Early the high sensitivity for identifying tumor progression, FET-PET MR postoperative MR imaging may be ambiguous for residual tumors. imaging could change clinical management in nearly one-half of In 25 patients with HGGs, FET-PET, MR imaging, and intraoper- patients. ative assessment consistently showed complete resection in 48% Monitoring Treatment Response to Newer Drugs in Recurrent of cases and residual disease in 24%. A Prospective PET/MRI HGGs. AAT-PET can predict patient survival in both HGGs and study correlated the MET accumulation in GBM patients before LGGs treated with temozolomide. AAT-PET imaging reveals met- postoperative chemoradiation with time to recurrence. The abolic alterations in response to temozolomide earlier than mor- median time to recurrence was significantly shorter in MET-posi- phologic alterations on MR imaging. Dynamic TAC patterns are tive than MET-negative patients (6.3 and 19 months, P , .001). helpful for diagnostic and prognostic purposes, particularly in Rosen et al evaluated the prognostic value of dynamic FET-PET distinguishing progression from TRC. Bevacizumab is an anti- in partially resected IDH wild-type astrocytic gliomas with mini- angiogenic chemotherapy drug targeting circulating vascular mal or absent contrast enhancement. Smaller pre-irradiation endothelial growth factor and lowering cerebrovascular perme- FET-PET tumor volumes correlated with a favorable progression- ability. It is an adjunctive therapy in recurrent HGGs and signifi- free survival (7.9 versus 4.2 months; P ¼ .012) and overall survival cantly reduces contrast enhancement, underestimating residual (16.6 versus 9.0 months; P ¼ .002). In contrast, the mean TBR and tumor evaluation. FET, MET, and FDOPA-PET combined with time-to-peak values were associated with only a longer progres- multiparametric MRI have shown promising results for improv- sion-free survival (P ¼ .048 and P ¼ .045, respectively). ing accuracy in diagnosing tumor recurrence and detecting early Disease and Treatment Monitoring: Differentiation between treatment failure and TRC in patients with recurrent HGGs Tumor Recurrence and TRC. After initial glioma management, treated with bevacizumab. In a recurrent HGG in a patient on TRC are common and may mimic or coexist with tumor recur- bevacizumab, the relationship between response to therapy on rence. RANO criteria based on T2-weighted, FLAIR, and con- FET-PET and improved overall survival or progression-free sur- trast-enhancement changes are affected by BBB damage, which vival is not well-understood. Compared with MR imaging, FET- fails to differentiate tumor recurrence from treatment-related PET could determine the failure of bevacizumab therapy 9–10.5 changes. In 20%–30% of patients, early postirradiation MR imag- weeks earlier and a change in diagnosis or treatment planning in ing exhibited increased enhancement, mimicking progression. one-third of patients. However, it gradually disappeared without intervention. TRC The response assessment after immunotherapy in gliomas can appear as new sites of enhancement or an increased extent of continues to be a significant challenge due to the rising occur- enhancement. Multiparametric MRI has certain limitations in rence of pseudoprogression. In patients with recurrent HGGs AJNR Am J Neuroradiol 44:236–46 Mar 2023 www.ajnr.org 241 Therapy Oncology Group protocol suggests the possibility of microscopic disease in this region and includes it in thetarget volumewith a lower pre- scribed radiation dose. In contrast, the European Society for Radiation Therapy and Oncology protocols do not specifically target this region. However, identifying this zone to pre- cisely cover the target volume with the appropriate radiation dose is essential for treatment. AA-PET could image the nonenhancing areas better than conventional MR imaging or FDG (Fig 4). In a biopsy-validated analy- sis, combined FDOPA-PET MR imag- ing detected high-grade subregions with an accuracy of 58% compared with 42% with contrast-enhanced MR imaging (P ¼ .03). The hybrid tech- nique leads to larger delineation vol- umes and better accuracy for detecting high-grade subregions. In GBM, AA- FIG 5. A 35-year-old man was treated for left frontal glioma (grade II), status post surgical resec- PET MR imaging helps to clarify the tion and chemoradiation in 2009. He underwent a reoperation in February 2018 for tumor recur- nature of the suspected nonenhancing rence. In June 2019, [ F] DOPA PET MR imaging (A–C) showed a postresection surgical cavity in region (Figs 5 and 6). It improves delin- the left anterior parasagittal basifrontal region without nodular enhancement or any increased eation of the radiation therapy target, focal FDOPA uptake. There was no evidence of recurrence. In June 2020, follow-up [ F]-DOPA PET MR imaging (D and E) showed a new focal nodular enhancing lesion in the left basifrontal thus reducing undertreatment. area (arrow) on the postcontrast T1-weighted image (D), with mildly increased rCBV perfusion (E) and corresponding increased FDOPA uptake on fused FET-PET MR imaging (F)(maximum standard Future Perspectives: Newer uptake value ¼ 3.9; lesion/striatal ratio; 1.38; ,1.0 as normal), suggesting recurrence. The patient Advances and Novel Radiotracers underwent a reoperation with recurrence found. This case also highlights the congruent ﬁndings Numerous non-AA tracers demon- on contrast-enhanced MR imaging and FDOPA-PET in differentiating TRC from recurrence. CE strate uptake in gliomas, but the PET indicates contrast-enhanced. signal is frequently not solely attrib- uted to the tumor cells. Glutamine- treated with regorafenib (multikinase inhibitor), FET and DWI- increased concentration in gliomas correlates with tumor prolif- ADC metrics can predict the overall survival, and could serve as eration and treatment resistance. The glutamine fluoro-analog, 4- semiquantitative independent biomarkers of response to treat- [ F]-(2S,4R)-fluoroglutamine distinguishes proliferating gliomas 46 50 ment. A recent study analyzed data from patients with GBM from stable tumors. The extracellular matrix, stromal cells, who received autologous dendritic cell vaccination therapy. In immune cells, and blood vessels comprise the tumor microenvir- MR imaging for suspicion for GBM recurrence, FET-PET onment contributing to tumorigenesis. New therapeutic showed congruent tumor progression in 3/5 patients and TRC in approaches target tumor microenvironment cells, necessitating the remaining 2/5. AAT-PET may help to identify the personal- the discovery of relevant imaging biomarkers to identify individ- 51 18 ized bevacizumab treatment dose to improve therapeutic efficacy. uals who benefit from such therapy. [ F]DPA-714(TSPO)-PET Tumor volumetric and ADC analyses of serial MR imaging scans MR imaging is used to image the glioma-associated immunosup- from 67 patients and serial FET-TBRs from 31 patients revealed pressive tumor microenvironment for targeting immunotherapy, overall survival benefits from bevacizumab plus radiation therapy drug target engagement, and clinical response assessment. compared with radiation alone. A high FET-TBR of nonenhanc- Intratumoral hypoxia is associated with resistance to treat- ment and entails radiation to hypoxic subregions of tumors. [ F] ing tumor portions during bevacizumab therapy was associated with an inferior overall survival on multivariate analysis (hazard fluoromisonidazole, a nitroimidazole derivative that images via- ratio, 5.97; 95% CI, 1.16–30.8). ble hypoxic cells, a biomarker of glioblastoma that correlates with prolonged overall survival and distinguishes pseudoprogression Role in Nonenhancing Tumors. Most LGGs do not grossly dis- from recurrence in patients with HGGs treated with pembrolizu- 54 18 rupt BBBs, and many HGGs have nonenhancing regions subopti- mab [ F]-GE-180 (a novel TSPO ligand), is an imaging bio- mally evaluated on conventional MR imaging. In GBM, FLAIR marker of tumor heterogeneity with improved binding affinity changes adjacent to an enhancement are presumed to be related and a high TBR in glioblastoma. TSPO-PET can differentiate to edema, which alters radiation protocols. The Radiation potentially aggressive forms of gliomas, graded according to the 242 Soni Mar 2023 www.ajnr.org activation protein gallium 68-labeled fibroblast activation protein inhibitor [ Ga]FAPI shows high accumulation in IDH wild-type WHO grade IV glio- mas and WHO grade III and IV glio- mas compared with WHO grade II gliomas. Although non-AA tracers are not specific for tumor cell imaging, they might still be used to better delin- eate tumor extent and, more important, as radiotheranostic agents. However, theresults arevery preliminary, and validation studies are required. Application of Feature-Based PET MR Imaging Radiomics in Patients with Gliomas Radiomics allows the voxel-level extrac- tion of quantitative features from vari- ous diagnostic imaging integrated with clinical, histopathologic, and molecular factors to produce diagnostic, prognos- tic, or predictive mathematic models. Several PET radiomics analyses have been performed in neuro-oncology with reasonable accuracy to predict the glioma grade and identify the IDH mutation and the patients with a high risk of progression after receiving first- line therapy. FET-PET MR imaging combined with textural analysis predicts IDH mutations at 93%. The proposed machine learning model on MET-PET can predict grades of disease. FET- radiomic features discriminated signifi- cantly between tumor and nontumor components of 32 patients with recur- rent GBM. Thetexture featureshowed the best performance for predicting time to progression and overall survival and localizing the site of recurrence. The authors postulated that FET-PET FIG 6. A 37-year-old man with a known diagnosis of oligodendroglioma, status post resection radiomics might help with prognostic and chemoradiation. Postcontrast T1-weighted image (A, blue arrow) shows a recurrent enhanc- evaluation and selecting patients with ing lesion along the inferomedial aspect of the resection cavity of the right frontal region involv- recurrent GBM who would benefit ing the body of the corpus callosum. Fused-PET MR images (B and C) show intralesional increased FDG slightly higher than in the white matter and lower than in the gray matter with increased from re-irradiation. Further studies rCBV perfusion (D, white arrows). Fused FET-PET MR images (E and F) show a relatively larger vol- are needed to improve radiomics algo- ume of a recurrent lesion, allowing better estimates of the extent of the lesion. Multivoxel MRS rithms to personalize predictive and (G) shows an increased choline peak and decreased NAA peak. The pathologic diagnosis was a re- prognostic models and potentially sup- currence. This case highlights the superiority of AAT over FDG, congruent ﬁndings on MR imaging port the medical decision process. and FET-PET, and an excellent TBR, which were helpful in radiation therapy planning and re-surgi- cal resection. CE indicates contrast-enhanced. Cost-Effectiveness of Treatment Monitoring of Gliomas Using AAT-PET World Health Organization (WHO) classification, with a positive It is crucial to ensure that financial resources are used as efficiently rate on PET of 100% among the HGGs. The Arg-Gly-Asp pep- as possible, given the limited resources available for health care. tide is an angiogenesis-targeting radiotracer that binds avb 3 Imaging techniques require substantial investment. They should integrins and monitors antiangiogenic therapies. The fibroblast preferably be used only when the extra value appears to justify the AJNR Am J Neuroradiol 44:236–46 Mar 2023 www.ajnr.org 243 3 expense. The known benefit of AAT-PET in patients with glioma oligodendroglial tumors. A significant proportion (30%) of is to prevent unnecessary treatment and its side effects. Joint rec- grade II IDH-mutated gliomas do not exhibit considerable AAT ommendations state that AAT-PET MR imaging is appropriate uptake. A negative finding on AA-PET is insufficient to exclude 68,69 for clinical use and FET-PET is the most useful for predicting LGGs. 62,63 treatment responses of glioblastomas. Despite the ubiquitous use of PET MR imaging, the FDA requires the treating institution CONCLUSIONS to obtain an Investigational New Drug Application, which has In the current era of precision and personalized medicine, AAT- prevented the mainstream adoption of AAT-PET into the neuro- PET can provide additional insight beyond MR imaging for the oncology clinical algorithm in the United States. clinical management of brain tumors (Online Supplemental Heinzel et al evaluated the cost-effectiveness of FET-PET Data). Furthermore, sufficient literature is available to demon- MR imaging–guided biopsy for diagnosing gliomas. FET-PET strate the utility of AAT-PET MR imaging in distinguishing re- MR imaging resulted in an increase of 18.5% in the likelihood of currence from TRC in gliomas. There are several limitations in a correct diagnosis. The incremental cost-effectiveness ratio for 1 the existing literature, which may have impacted the diagnostic additional accurate diagnosis was e6405 for the baseline scenario efficacy of the radionuclide tracers. Prospective validation studies and e9114 for the scenario based on higher disease severity. of PET imaging criteria are needed to get beyond these restric- Heinzel et al investigated the cost-effectiveness of recurrent tions and allow comparisons of direct results. Even though hybrid HGGs treated with bevacizumab and irinotecan. The authors PET MR imaging is more patient-friendly and offers practical suggested that the additional use of FET-PET in managing advantages, the cost-effectiveness and accessibility of these sys- patients may be cost-effective. Baguet et al evaluated the cost- tems must be weighed against the additional effort involved in se- effectiveness of a follow-up PET scan performed on patients with quential examinations. As a result, it is projected that more glioblastoma postsurgery and before temozolomide. The decision effective therapy monitoring will be available in the upcoming tree based on overall survival demonstrated that the number of years, which may be beneficial for glioma management. nonresponders identified using PET was 57.14% higher than that with conventional MR imaging. Disclosure forms provided by the authors are available with the full text and PDF of this article at www.ajnr.org. AATs need to be FDA-approved to become widely available and approved by the Centers for Medicare and Medicaid Services REFERENCES to be reimbursable. Cost-effective analyses of hybrid PET MR 1. Lin D, Wang M, Chen Y, et al. Trends in intracranial glioma inci- imaging scanners are still pending. Further work is needed to dence and mortality in the United States, 1975-2018. Front Oncol update treatment guidelines and to include more PET agents 2021;11:748061 CrossRef Medline when appropriate, encouraging insurance companies to reim- 2. Ostrom QT, Gittleman H, Liao P, et al. CBTRUS Statistical Report: burse for these potentially valuable agents. A simple-but-effec- primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol 2017;19:v1–88 tive solution to the limited availability, use, and cost-effectiveness CrossRef Medline of the hybrid PET MR imaging remains to standardize the proto- 3. Law I, Albert NL, Arbizu J, et al. Joint EANM/EANO/RANO prac- col for separate PET and MR imaging acquisitions. tice guidelines/SNMMI procedure standards for imaging of glio- mas using PET with radiolabelled amino acids and [(18)F]FDG: Limitations of AATs version 1.0. Eur J Nucl Med Mol Imaging 2019;46:540–57 CrossRef Combining PET and MR imaging is more patient-friendly than Medline 4. Soni N, Ora M, Mohindra N, et al. Diagnostic performance of PET separate examinations and avoids the limitations of each imaging and perfusion-weighted imaging in differentiating tumor recur- technique. With the development of PET MR imaging, it is now rence or progression from radiation necrosis in posttreatment possible to swiftly and effectively study a variety of PET and MR gliomas: a review of literature. AJNR Am J Neuroradiol 2020;41: imaging parameters. Significant hurdles include accessibility, the 1550–57 CrossRef Medline cost of PET MR imaging examinations, and the limited availabil- 5. de Zwart PL, van Dijken BR, Holtman GA, et al. Diagnostic accuracy of PET tracers for the differentiation of tumor progression from ity of the AATs. Uncertainty exists regarding the cost-effective- treatment-related changes in high-grade glioma: a systematic ness of PET MR imaging and the patients who will benefit from review and metaanalysis. J Nucl Med 2020;61:498–504 CrossRef combined PET MR imaging. AATs have known limitations, with Medline false-positive results in inflammation, infection, postsurgical 6. Cui M, Zorrilla-Veloz RI, Hu J, et al. Diagnostic accuracy of PET for regions, and postchemoradiation. Small tumor volumes may differentiating true glioma progression from post treatment- related changes: a systematic review and meta-analysis. Front lead to false-negative results due to the partial volume effect. Neurol 2021;12:671867 CrossRef Medline Acquisition of a baseline scan helps to compare pre- and post- 7. Moreau A, Febvey O, Mognetti T, et al. Contribution of different treatment imaging findings. The estimation of TBR mean, TBR positron emission tomography tracers in glioma management: maximum, and BTV with AATs relies on reference brain paren- focus on glioblastoma. Front Oncol 2019;9:9 CrossRef Medline chymal uptake. A decreased uptake due to atrophy, trauma, 8. Lopes C, Pereira C, Medeiros R. ASCT2 and LAT1 contribution to the hallmarks of cancer: from a molecular perspective to clinical infarcts, and ischemia may lead to overestimating parameters. translation. Cancers (Basel) 2021;13:203 CrossRef Medline Initial dynamic FET images may show a reasonably high blood- 9. Hughes KL, O’Neal CM, Andrews BJ, et al. A systematic review of pool uptake, and TAC in vascular structures may resemble tumor the utility of amino acid PET in assessing treatment response to uptake. An increasing TAC may indicate inflammatory lesions, bevacizumab in recurrent high-grade glioma. Neurooncol Adv while a decreasing TAC may be seen in WHO grade II 2021;3:vdab003 CrossRef Medline 244 Soni Mar 2023 www.ajnr.org 10. Fuchs BC, Bode BP. Amino acid transporters ASCT2 and LAT1 28. Laack NN, Pafundi D, Anderson SK, et al. Initial results of a Phase 2 in cancer: partners in crime? Semin Cancer Biol 2005;15:254–66 trial of (18)F-DOPA PET-guided dose-escalated radiation therapy CrossRef Medline for glioblastoma. Int J Radiat Oncol Biol Phys 2021;110:1383–95 11. Jansen NL, Suchorska B, Wenter V, et al. Dynamic 18F-FET PET in CrossRef Medline 29. Dissaux G, Dissaux B, Kabbaj OE, et al. Radiotherapy target volume newly diagnosed astrocytic low-grade glioma identifies high-risk definition in newly diagnosed high grade glioma using (18)F-FET patients. JNucl Med 2014;55:198–203 CrossRef Medline PET imaging and multiparametric perfusion MRI: a prospective 12. Jansen NL, Graute V, Armbruster L, et al. MRI-suspected low-grade study (IMAGG). Radiother Oncol 2020;150:164–71 CrossRef Medline glioma: is there a need to perform dynamic FET PET? Eur J Nucl 30. Filss CP, Galldiks N, Stoffels G, et al. Comparison of 18F-FET PET Med Mol Imaging 2012;39:1021–29 CrossRef Medline and perfusion-weighted MR imaging: a PET/MR imaging hybrid 13. Jansen NL, Schwartz C, Graute V, et al. Prediction of oligodendro- study in patients with brain tumors. JNucl Med 2014;55:540–45 glial histology and LOH 1p/19q using dynamic [(18)F]FET-PET CrossRef Medline imaging in intracranial WHO grade II and III gliomas. Neuro 31. Lohmann P, Stavrinou P, Lipke K, et al. FET PET reveals consider- Oncol 2012;14:1473–80 CrossRef Medline able spatial differences in tumour burden compared to conven- 14. Brendle C, Maier C, Bender B, et al. Impact of (18)F-FET PET/MRI tional MRI in newly diagnosed glioblastoma. Eur J Nucl Med Mol on clinical management of brain tumor patients. JNucl Med 2022; Imaging 2019;46:591–602 CrossRef Medline 63:522–27 CrossRef Medline 32. Hayes AR, Jayamanne D, Hsiao E, et al. Utilizing 18F-fluoroethyl- 15. Furtak J, Rakowska J, Szylberg T, et al. Glioma biopsy based on tyrosine (FET) positron emission tomography (PET) to define sus- hybrid dual time-point FET-PET/MRI: a proof of concept study. pected nonenhancing tumor for radiation therapy planning of Front Neurol 2021;12:634609 CrossRef Medline glioblastoma. Pract Radiat Oncol 2018;8:230–38 CrossRef Medline 16. Göttler J, Lukas M, Kluge A, et al. Intra-lesional spatial correlation 33. Kläsner B, Buchmann N, Gempt J, et al. Early [18F]FET-PET in glio- of static and dynamic FET-PET parameters with MRI-based cere- mas after surgical resection: comparison with MRI and histopa- bral blood volume in patients with untreated glioma. Eur J Nucl thology. PLoS One 2015;10:e0141153 CrossRef Medline Med Mol Imaging 2017;44:392–97 CrossRef Medline 34. Seidlitz A, Beuthien-Baumann B, Löck S, et al. Final results of the 17. Ort J, Hamou HA, Kernbach JM, et al. (18)F-FET-PET-guided gross Prospective Biomarker Trial PETra: [(11)C]-MET-accumulation total resection improves overall survival in patients with WHO in postoperative PET/MRI predicts outcome after radiochemo- grade III/IV glioma: moving towards a multimodal imaging- therapy in glioblastoma. Clin Cancer Res 2021;27:1351–60 CrossRef guided resection. JNeurooncol 2021;155:71–80 CrossRef Medline Medline 18. Xiao J, Jin Y, Nie J, et al. Diagnostic and grading accuracy of (18)F- 35. Rosen J, Stoffels G, Lohmann P, et al. Prognostic value of pre-irradi- FDOPA PET and PET/CT in patients with gliomas: a systematic ation FET PET in patients with not completely resectable IDH- review and meta-analysis. BMC Cancer 2019;19:767 CrossRef wildtype glioma and minimal or absent contrast enhancement. Sci Medline Rep 2021;11:20828 CrossRef Medline 19. Verger A, Filss CP, Lohmann P, et al. Comparison of (18)F-FET 36. Ellingson BM, Chung C, Pope WB, et al. Pseudoprogression, radio- PET and perfusion-weighted MRI for glioma grading: a hybrid necrosis, inflammation or true tumor progression? Challenges PET/MR study. Eur J Nucl Med Mol Imaging 2017;44:2257–65 associated with glioblastoma response assessment in an evolving CrossRef Medline therapeutic landscape. J Neurooncol 2017;134:495–504 CrossRef 20. Girard A, Le Reste PJ, Metais A, et al. Combining (18)F-DOPA PET Medline and MRI with perfusion-weighted imaging improves delineation 37. Albert NL, Weller M, Suchorska B, et al. Response Assessment in of high-grade subregions in enhancing and non-enhancing glio- Neuro-Oncology Working Group and European Association for mas prior treatment: a biopsy-controlled study. J Neurooncol Neuro-Oncology recommendations for the clinical use of PET 2021;155:287–95 CrossRef Medline imaging in gliomas. Neuro Oncol 2016;18:1199–208 CrossRef 21. Osborn AG, Louis DN, Poussaint TY, et al. The 2021 World Health Medline Organization Classification of Tumors of the Central Nervous 38. Galldiks N, Niyazi M, Grosu AL, et al. Contribution of PET imaging System: what neuroradiologists need to know. AJNR Am J Neuro- to radiotherapy planning and monitoring in glioma patients: a radiol 2022;43:928–37 CrossRef Medline report of the PET/RANO group. Neuro Oncol 2021;23:881–93 22. Song S, Wang L, Yang H, et al. Static (18)F-FET PET and DSC-PWI CrossRef Medline based on hybrid PET/MR for the prediction of gliomas defined by 39. Deuschl C, Kirchner J, Poeppel TD, et al. 11C-MET PET/MRI for IDH and 1p/19q status. Eur Radiol 2021;31:4087–96 CrossRef detection of recurrent glioma. Eur J Nucl Med Mol Imaging 2018; Medline 45:593–601 CrossRef Medline 23. Tatekawa H, Yao J, Oughourlian TC, et al. Maximum uptake and 40. D’Souza MM, Sharma R, Jaimini A, et al. 11C-MET PET/CT and hypermetabolic volume of 18F-FDOPA PET estimate molecular advanced MRI in the evaluation of tumor recurrence in high-grade status and overall survival in low-grade gliomas: a PET and MRI gliomas. Clin Nucl Med 2014;39:791–98 CrossRef Medline study. Clin Nucl Med 2020;45:e505–11 CrossRef Medline 41. Steidl E, Langen KJ, Hmeidan SA, et al. Sequential implementation 24. Kim D, Chun JH, Kim SH, et al. Re-evaluation of the diagnostic per- of DSC-MR perfusion and dynamic [(18)F]FET PET allows effi- formance of (11)C-methionine PET/CT according to the 2016 cient differentiation of glioma progression from treatment-related WHO classification of cerebral gliomas. Eur J Nucl Med Mol changes. Eur J Nucl Med Mol Imaging 2021;48:1956–65 CrossRef Imaging 2019;46:1678–84 CrossRef Medline Medline 25. Cheng Y, Song S, Wei Y, et al. Glioma imaging by O-(2-18F-fluo- 42. Werner JM, Weller J, Ceccon G, et al. Diagnosis of pseudoprogres- roethyl)-L-tyrosine PET and diffusion-weighted MRI and correla- sion following lomustine-temozolomide chemoradiation in newly tion with molecular phenotypes, validated by PET/MR-guided diagnosed glioblastoma patients using FET-PET. Clin Cancer Res biopsies. Front Oncol 2021;11:743655 CrossRef Medline 2021;27:3704–13 CrossRef Medline 26. Haubold J, Demircioglu A, Gratz M, et al. Non-invasive tumor 43. Pellerin A, Khalifé M, Sanson M, et al. Simultaneously acquired PET decoding and phenotyping of cerebral gliomas utilizing multipara- and ASL imaging biomarkers may be helpful in differentiating metric (18)F-FET PET-MRI and MR fingerprinting. Eur J Nucl progression from pseudo-progression in treated gliomas. Eur Med Mol Imaging 2020;47:1435–45 CrossRef Medline Radiol 2021;31:7395–405 CrossRef Medline 27. Meyer HS, Liesche-Starnecker F, Mustafa M, et al. (18)F FET PET 44. Prather KY, O’Neal CM, Westrup AM, et al. A systematic review of uptake indicates high tumor and low necrosis content in brain me- amino acid PET in assessing treatment response to temozolomide tastasis. Cancers (Basel) 2021;13:355 CrossRef Medline in glioma. Neurooncol Adv 2022;4:vdac008 CrossRef Medline AJNR Am J Neuroradiol 44:236–46 Mar 2023 www.ajnr.org 245 45. Harris RJ, Cloughesy TF, Pope WB, et al. 18F-FDOPA and 18F-FLT 57. Rohrich M, Loktev A, Wefers AK, et al. IDH-wildtype glioblastomas positron emission tomography parametric response maps predict and grade III/IV IDH-mutant gliomas show elevated tracer uptake response in recurrent malignant gliomas treated with bevacizu- in fibroblast activation protein-specific PET/CT. Eur J Nucl Med mab. Neuro Oncol 2012;14:1079–89 CrossRef Medline Mol Imaging 2019;46:2569–80 CrossRef Medline 46. Lombardi G, Spimpolo A, Berti S, et al. PET/MR in recurrent glio- 58. Lohmann P, Meißner AK, Kocher M, et al. Feature-based PET/MRI blastoma patients treated with regorafenib: [(18)F]FET and DWI- radiomics in patients with brain tumors. Neurooncol Adv 2020;2: ADC for response assessment and survival prediction. Br J Radiol iv15–21 CrossRef Medline 2022;95:20211018 CrossRef Medline 59. Lohmann P, Lerche C, Bauer EK, et al. Predicting IDH genotype in 47. Kristin Schmitz A, Sorg RV, Stoffels G, et al. Diagnostic impact of gliomas using FET PET radiomics. Sci Rep 2018;8:13328 CrossRef additional O-(2-[18F]fluoroethyl)-L-tyrosine ((18)F-FET) PET fol- Medline lowing immunotherapy with dendritic cell vaccination in glioblas- 60. Russo G, Stefano A, Alongi P, et al. Feasibility on the use of radio- toma patients. Br J Neurosurg 2021;35:736–42 CrossRef Medline mics features of 11[C]-MET PET/CT in central nervous system 48. Wirsching HG, Roelcke U, Weller J, et al. MRI and (18)FET-PET tumours: preliminary results on potential grading discrimination predict survival benefit from bevacizumab plus radiotherapy in using a machine learning model. Curr Oncol 2021;28:5318–31 patients with isocitrate dehydrogenase wild-type glioblastoma: CrossRef Medline results from the randomized ARTE Trial. Clin Cancer Res 61. Carles M, Popp I, Starke MM, et al. FET-PET radiomics in recurrent 2021;27:179–88 CrossRef Medline glioblastoma: prognostic value for outcome after re-irradiation? 49. Niyazi M, Brada M, Chalmers AJ, et al. ESTRO-ACROP guideline Radiat Oncol 2021;16:46 CrossRef Medline “target delineation of glioblastomas.” Radiother Oncol 2016;118:35– 62. Langen KJ, Galldiks N. Update on amino acid pet of brain tumours. 42 CrossRef Medline Curr Opin Neurol 2018;31:354–61 CrossRef Medline 50. Ekici S, Nye JA, Neill SG, et al. Glutamine imaging: a new avenue 63. Langen K-J, Heinzel A, Lohmann P, et al. Advantages and limita- for glioma management. AJNR Am J Neuroradiol 2022;43:11–18 tions of amino acid PET for tracking therapy response in glioma CrossRef Medline patients. Expert Rev Neurother.2020;20:137–46 CrossRef Medline 51. Anderson NM, Simon MC. The tumor microenvironment. Curr 64. Heinzel A, Stock S, Langen K-J, et al. Cost-effectiveness analysis of Biol 2020;30:R921–25 CrossRef Medline FET PET-guided target selection for the diagnosis of gliomas. Eur 52. Zinnhardt B, Müther M, Roll W, et al. TSPO imaging-guided char- JNucl Med Mol Imaging 2012;39:1089–96 CrossRef Medline acterization of the immunosuppressive myeloid tumor microen- 65. Heinzel A, Müller D, Langen KJ, et al. The use of O-(2-18F-fluo- vironment in patients with malignant glioma. Neuro Oncol roethyl)-L-tyrosine PET for treatment management of bevacizu- 2020;22:1030–43 CrossRef Medline mab and irinotecan in patients with recurrent high-grade glioma: 53. Leimgruber A, Hickson K, Lee ST, et al. Spatial and quantitative a cost-effectiveness analysis. JNucl Med 2013;54:1217–22 CrossRef mapping of glycolysis and hypoxia in glioblastoma as a predictor Medline of radiotherapy response and sites of relapse. Eur J Nucl Med Mol 66. Baguet T, Verhoeven J, De Vos F, et al. Cost-effectiveness of [18F] Imaging 2020;47:1476–85 CrossRef Medline fluoroethyl-L-tyrosine for temozolomide therapy assessment in 54.Barajas RF Jr,Ambady P,Link J,et al. [(18)F]-fluoromisonidazole patients with glioblastoma. Front Oncol 2019;9:9 CrossRef (FMISO) PET/MRI hypoxic fraction distinguishes neuroinflamma- 67. Ehman EC, Johnson GB, Villanueva-Meyer JE, et al. PET/MRI: tory pseudoprogression from recurrent glioblastoma in patients Where might it replace PET/CT? J Magn Reson Imaging 2017;46: treated with pembrolizumab. Neurooncol Pract 2022;9:246–50 1247–62 CrossRef Medline CrossRef Medline 68. Suchorska B, Giese A, Biczok A, et al. Identification of time-to-peak 55. Unterrainer M, Fleischmann DF, Vettermann F, et al. TSPO PET, on dynamic 18F-FET-PET as a prognostic marker specifically in tumour grading and molecular genetics in histologically verified IDH1/2 mutant diffuse astrocytoma. Neuro Oncol 2018;20:279–88 glioma: a correlative (18)F-GE-180 PET study. Eur J Nucl Med Mol CrossRef Medline Imaging 2020;47:1368–80 CrossRef Medline 69. Zhang-Yin JT, Girard A, Bertaux M. What does PET imaging bring 56. Echavidre W, Picco V, Faraggi M, et al. Integrin-avb 3 as a thera- to neuro-oncology in 2022? a review. Cancers (Basel) 2022;14:879 peutic target in glioblastoma: back to the future? Pharmaceutics 2022;14:1054 CrossRef Medline CrossRef Medline 246 Soni Mar 2023 www.ajnr.org
American Journal of Neuroradiology – American Journal of Neuroradiology
Published: Mar 1, 2023
Access the full text.
Sign up today, get DeepDyve free for 14 days.