Review The Role of PET in Supratentorial and Infratentorial Pediatric Brain Tumors Angelina Cistaro 1,2 , Domenico Albano 3 , Pierpaolo Alongi 4,* , Riccardo Laudicella 5 , Daniele Antonio Pizzuto 6 , Giuseppe Formica 5, Cinzia Romagnolo 7, Federica Stracuzzi 5, Viviana Frantellizzi 8 , Arnoldo Piccardo 1,2 and Natale Quartuccio 2,9 1 Nuclear Medicine Department, Ospedali Galliera, 16128 Genova, Italy; [email protected] (A.C.); [email protected] (A.P.) 2 AIMN Pediatric Study Group, 20159 Milan, Italy; [email protected] 3 Department of Nuclear Medicine, University of Brescia and Spedali Civili Brescia, 25123 Brescia, Italy; [email protected] 4 Unit of Nuclear Medicine, Fondazione Istituto G. Giglio, 90015 Cefalù, Italy 5 Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, A.O.U. Policlinico G. Martino, University of Messina, 98125 Messina, Italy; [email protected] (R.L.); [email protected] (G.F.); [email protected] (F.S.) 6 Department of Nuclear Medicine, University Hospital Zürich, 8091 Zürich, Switzerland; [email protected] 7 Nuclear Medicine Unit, Ospedali Riuniti, Torrette di Ancona, 60126 Ancona, Italy; [email protected] 8 Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, 00161 Rome, Italy; [email protected] 9 Nuclear Medicine Unit, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, 90127 Palermo, Italy * Correspondence: [email protected] Abstract: Objective: This review aims to provide a summary of the clinical indications and limitations Citation: Cistaro, A.; Albano, D.; of PET imaging with different radiotracers, including 18F-fluorodeoxyglucose (18F-FDG) and other Alongi, P.; Laudicella, R.; Pizzuto, radiopharmaceuticals, in pediatric neuro-oncology, discussing both supratentorial and infratentorial D.A.; Formica, G.; Romagnolo, C.; Stracuzzi, F.; Frantellizzi, V.; Piccardo, tumors, based on recent literature (from 2010 to present). Methods: A literature search of the A.; et al. The Role of PET in PubMed/MEDLINE database was carried out searching for articles on the use of PET in pediatric Supratentorial and Infratentorial brain tumors. The search was updated until December 2020 and limited to original studies published Pediatric Brain Tumors. Curr. Oncol. in English after 1 January 2010. Results: 18F-FDG PET continues to be successfully employed in 2021, 28, 2481–2495. https:// different settings in pediatric neuro-oncology, including diagnosis, grading and delineation of the doi.org/10.3390/curroncol28040226 target for stereotactic biopsy, estimation of prognosis, evaluation of recurrence, treatment planning and assessment of treatment response. Nevertheless, non-18F-FDG tracers, especially amino acid Received: 18 May 2021 analogues seem to show a better performance in each clinical setting. Conclusions: PET imaging Accepted: 29 June 2021 adds important information in the diagnostic work-up of pediatric brain tumors. International or Published: 5 July 2021 national multicentric studies are encouraged in order to collect larger amount of data. Publisher’s Note: MDPI stays neutral Keywords: positron emission tomography; brain tumors; pediatrics with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Central nervous system (CNS) tumors constitute a heterogeneous group of benign and malignant neoplasms with an incidence of 2.99 cases per 100,000 children in Europe [1]. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Primary CNS tumors are divided according to their tissue of origin into glial and non-glial This article is an open access article tumors. Gliomas constitute the most frequent group of brain tumors in the pediatric distributed under the terms and population, with pilocytic astrocytoma and brain glioma representing the most common conditions of the Creative Commons type, with an incidence of approximately 17% and 10%, respectively [1,2]. Attribution (CC BY) license (https:// Another important distinction for pediatric brain tumors, which also influences the creativecommons.org/licenses/by/ surgical approach, is based on the location with respect to the tentorium (supra- and in- 4.0/). fratentorial) [3]. Differently from adults, most pediatric tumors are infratentorial (approxi- Curr. Oncol. 2021, 28, 2481–2495. https://doi.org/10.3390/curroncol28040226 https://www.mdpi.com/journal/curroncol Curr. Oncol. 2021, 28, 2 Curr. Oncol. 2021, 28, 2 Curr. Oncol. 2021, 28 2482 Another important distinction for pediatric brain tumors, which also influences the surgicalAnother approach, important is based distinction on the for location pediatric with brain respect tumors, to the which tentorium also influences (supra- andthe surgicalinfratentorial) approach, [3]. isDifferently based on fromthe location adults, withmost respect pediatric to thetumors tentorium are infratentorial (supra- and matelyinfratentorial)(approximately 60% of all[3]. 60% CNS Differently of tumors) all CNS and from tumors) encompass adults, and juvenilemostencompass pediatric pilocytic juvenile tumors astrocytoma pilocytic are (JPA),infratentorial astrocytoma medul- loblastoma(approximately(JPA), medulloblastoma (Figure 60%1), of ependymoma, all (Figure CNS 1),tumors) ependymoma, diffuse and intrinsicencompass diffuse pontine intrinsicjuvenile glioma pontinepilocytic (DIPG; glioma astrocytomaFigure (DIPG;2) and(JPA),Figure atypical medulloblastoma 2) and teratoid atypical rhabdoid teratoid (Figure tumor rhabdoid1), ependymoma, (ATRT) tumor [4, 5(ATRT)]. diffuse Supratentorial [4,5].intrinsic Supratentorial pontine tumors glioma are tumors located (DIPG; are in theFigurelocated cerebral 2) in and the hemispheres cerebralatypical hemispheresteratoid and are rhabdoid more and commonare tu mormore (ATRT) incommon the youngest[4,5]. in theSupratentorial youngest patients; theypatients; tumors include they are astrocytomas,locatedinclude inastrocytomas, the cerebral gangliogliomas hemispheres gangliogliomas (Figure and3), are(Figure craniopharyngiomas, more 3), common craniopharyngiomas, in the supratentorial youngest supratentorialpatients; primitive they neuroectodermalincludeprimitive astrocytomas, neuroectodermal tumors gangliogliomas (PNET), tumors germ (PNET),(Figure cell tumors, 3),germ craniopharyngiomas, dysembryoplastic cell tumors, dysembryoplastic neuroepithelial supratentorial tumorsprimitiveneuroepithelial (DNET), neuroectodermal tumors oligodendrogliomas, (DNET), tumors oligod and(PNET),endrogliomas, meningiomas germ and [cell4]. meningiomas tumors, dysembryoplastic [4]. neuroepithelial tumors (DNET), oligodendrogliomas, and meningiomas [4]. FigureFigure 1.1.Transaxial Transaxial CT CT ( A(A),), PET PET ( B(B)) and and fused fused PET/CT PET/CT (C) and maximum intensity projection ( D) Figure 1. Transaxial CT (A), PET (B) and fused PET/CT (C) and maximum intensity projection (D) imagesimages of of a a medulloblastoma. medulloblastoma. images of a medulloblastoma. Figure 2. Transaxial CT (A), PET (B) and fused PET/CT (C) images of a pontine glioma. FigureFigure 2.2. TransaxialTransaxial CTCT ((AA),), PETPET ((BB)) andand fusedfused PET/CTPET/CT (C) images of a pontine glioma.glioma. Curr. Oncol. 2021, 28 2483 Curr. Oncol. 2021, 28, 3 FigureFigure 3.3.Transaxial Transaxial CTCT ((AA),), PET PET ((BB)) andand fusedfused PET/CTPET/CT ( C) and maximum intensity projection ( D) imagesimages of of a a frontal frontal ganglioglioma. ganglioglioma. TreatmentTreatment choice choice depends depends on on the the type type of tumor,of tumor, location, location, stage, stage, age andage clinicaland clinical con- ditions,conditions, preferring preferring local local surgery surgery to remove to remove the primary the primary lesion lesion [6]. The [6]. mainstay The mainstay of initial of diagnosticinitial diagnostic and pre-surgical and pre-surgical workup isworkup based onis contrast-enhancedbased on contrast-enhanced magnetic resonance magnetic imagingresonance (MRI) imaging with (MRI) gradient with echo, gradient standard echo, T2-weighted, standard T2-weighted, T2-fluid-attenuated T2-fluid-attenuated inversion recoveryinversion (FLAIR), recovery T1-weighted (FLAIR), T1-weighted and T1-weighted and T1-weighted contrast-enhanced contrast-enhanced sequences sequences [7]. Al- though[7]. Although having highhaving anatomical high anatomical resolution, resolution, conventional conventi MRIonal techniques MRI techniques may not be may able not to accuratelybe able to defineaccurately the extentdefine of the a tumorextent andof a distinguishtumor and distinguish tumor and surroundingtumor and surrounding infiltration frominfiltration normal from tissue, normal especially tissue, in especially the case of in non-focal the case pediatric of non-focal brain pediatric tumors, brain such astumors, optic pathwaysuch as gliomasoptic pathway and brainstem gliomas gliomas and [brainstem8]. The main gliomas limitation [8]. of The conventional main limitation MRI is the of lackconventional of specificity MRI of is the the signal lack of abnormality specificity of either the signal in T2 abnormality weighted imaging either (influencedin T2 weighted by tissueimaging water (influenced content), or by gadolinium-contrast tissue water conten enhancement,t), or gadolinium-contrast reflecting vascular enhancement, surface area andreflecting non-specific vascular increased surface permeabilityarea