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Imaging and Imaging-Based Treatment of Pheochromocytoma and Paraganglioma

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Imaging and Imaging-Based Treatment of Pheochromocytoma and Paraganglioma F Castinetti, K Pacak, PGL imaging 22:4 T135–T145 Thematic Review D Taieb et al. 15 YEARS OF PARAGANGLIOMA Imaging and imaging-based treatment of pheochromocytoma and paraganglioma Fre´de´ric Castinetti, Alexander Kroiss1, Rakesh Kumar2, Karel Pacak3,* and David Taieb4,5,* Department of Endocrinology, La Timone University Hospital, Aix-Marseille University, Marseille, France 1Department of Biophysics and Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria 2Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India 3Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Correspondence 4Department of Nuclear Medicine, European Center for Research in Medical Imaging (CERIMED), should be addressed La Timone University Hospital, Aix-Marseille University, 264, rue Saint-Pierre, 13385 Marseille, France to D Taieb 5Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille, France Email *(K Pacak and D Taieb contributed equally to this work) [email protected] Abstract Although anatomic imaging to assess the precise localization of pheochromocytomas/ Key Words paragangliomas (PHEOs/PGLs) is unavoidable before any surgical intervention on these " positron-emission Endocrine-Related Cancer tumors, functional imaging is becoming an inseparable portion of the imaging algorithm for tomography these tumors. This review article presents applications of the most up-to-date functional " gallium radioisotopes imaging modalities and image-based treatment to PHEOs/PGLs patients. Functional imaging " somatostatin 18 techniques provide whole-body localization (number of tumors present along with " F-DOPA 18 metastatic deposits) together with genetic-specific imaging approaches to PHEOs/PGLs, thus " F-FDG enabling highly specific and sensitive PHEO/PGL detection and delineation that now greatly impact the management of patients. Radionuclide imaging techniques also play a crucial role in the prediction of possible radioactive treatment options for PHEO/PGL. In contrast to previous imaging algorithms used for either assessement of these patients or their follow-up, endocrinologists, surgeons, oncologists, pediatricians, and other specialists require functional imaging before any therapeutic plan is outlined to the patient, and follow-up, especially in patients with metastatic disease, is based on the periodic use of functional imaging, often reducing or substituting for anatomical imaging. In similar specific indications, this will be further powered by using PET/MR in the assessment of these tumors. In the near future, it is expected that PHEO/PGL patients will benefit even more from an assessement of the functional characteristics of these tumors and new imaging-based treatment options. Finally, due to the use of new targeting moieties, gene-targeted radiotherapeutics and nanobodies- based theranostic approaches are expected to become a reality in the near future. Endocrine-Related Cancer (2015) 22, T135–T145 http://erc.endocrinology-journals.org q 2015 Society for Endocrinology This paper is part of a thematic review section on the 15th Anniversary of DOI: 10.1530/ERC-15-0175 Printed in Great Britain Paraganglioma and Pheochromocytoma. The Guest Editors for this section Published by Bioscientifica Ltd. were Wouter de Herder and HartmutDownloaded Neumann. from Bioscientifica.com at 09/27/2021 06:21:22PM via free access Thematic Review F Castinetti, K Pacak, PGL imaging 22:4 T136 D Taieb et al. Current approaches for localization of typical of PGL, with a ‘salt-and-pepper’ appearance on spin- pheochromocytomas/paragangliomas echo sequences. Magnetic resonance (MR) angiography also demonstrates intra-tumoral arterial vessels (Johnson Paragangliomas associated with the parasympathetic 1998, Arnold et al. 2003, van den Berg et al. 2004, van den nervous system Berg 2005, Neves et al. 2008). 3D time-of-flight (a non- Glomus tumors and other paragangliomas (PGLs) of contrast MR angiography), 3D gadolinium-enhanced MR parasympathetic origin develop from non-chromaffin angiography sequences, and, more recently, time-resolved organs that act as chemoreceptors and are mainly located 4D gadolinium MR angiography have been shown to be in glomus bodies (carotid body, aortic bodies) or highly informative in the detection of HNPGLs (Arnold embedded in several sensory parasympathetic ganglia. et al. 2003, van den Berg et al. 2004, Neves et al. 2008), Those located in the head and neck region are referred to especially JPs. Fusion images between T1-weighted and the as head and neck PGLs (HNPGLs). Carotid body PGL (CBP) most informative images on 4D MR angiography are is the most common location among all parasympathetic particularly useful for tumor delineation (Fig. 1). PGLs, followed by glomus jugulare (the jugular bulb in the CT offers several advantages over MRI (e.g., better jugular foramen, JP), glomus tympanicum or hypotympa- spatial resolution and less motion artifacts) and nicum (middle ear or hypotympanum, TP), and then enables better evaluation of the temporal bone extension glomus vagale (VP). The carotid body is a prime example of of JP and TP. MRI provides better soft-tissue contrast than a chemoreceptor organ that mediates reflex hyperventila- does CT and thus offers unique information for tumor tion during hypoxemia via activation of the respiratory delineation. center in the brain. Approximately two-thirds of HNPGLs do not usually Functional imaging To determine whether produce catecholamines but some may produce catechol- additional HNPGLs are present, anatomical imaging is amines and, if so, almost always produce dopamine, which inferior to PET/CT imaging. Therefore, it is currently is converted inside a tumor to 3-methoxytyramine – recommended that all patients with HNPGLs are assessed currently the best specific biomarker in the detection of by PET imaging. 18F-FDOPA, which enters cells via the these tumors (van Duinen et al. 2010, 2013, Eisenhofer et al. L-type amino acid transporter system, was considered 2012). 3-Methoxytyramine, which is elevated in 33% of the most sensitive imaging modality (sensitivity O90%) in Endocrine-Related Cancer patients with HNPGLs, supports this conclusion (van the detection of glomus tumors (King et al. 2011, Treglia Duinen et al. 2010, 2013). et al. 2012, Gabriel et al. 2013). The role of current imaging techniques is mainly to Recently, PET/CT imaging using 68Ga-labeled somato- diagnose HNPGL, determine tumor extension into the statin (SST) analogs has had excellent preliminary results bone and/or surrounding soft tissue, and rule out the (Maurice et al. 2012, Naji & Al-Nahhas 2012, Kroiss et al. presence of multiple tumors or local metastases, especially 2013, 2015, Sharma et al. 2013, Janssen et al. 2015). 68Ga- in lymph nodes. Evaluation of parapharyngeal space based PET imaging has lower intrinsic spatial resolution tumors involves careful consideration of clinical and and detection sensitivity compared to 18F-based PET imaging information to distinguish vagal PGLs from imaging (Sanchez-Crespo 2013), although these draw- peripheral nerve sheath tumors (schwannoma, neurofi- backs are partially compensated for in PGL imaging by broma), nodal metastases (nasopharynx/oropharynx, highly elevated tumor to background uptake ratios. thyroid cancer), other rare primary tumors, and a variety 68Ga-based PET imaging is rapidly evolving since it of uncommon miscellaneous lesions (Taieb et al. 2013). does not require a cyclotron to make the radiotracer. Previous and current studies from several centers Anatomic imaging Anatomic imaging serves as the worldwide suggest that this imaging modality will be as first-line modality in the locoregional staging of these effective as 18F-FDOPA PET/CT or even better; it may tumors. HNPGLs usually demonstrate marked enhance- surpass 18F-FDOPA PET in the near future also due to its ment of intra-tumoral vessels following contrast adminis- easier production, availability, and distribution (Fig. 2) tration on CT, low signal on T1-weighted images, and an (I Janssen, CC Chen, D Taieb, NJ Patronas, CM Millo, intermediate to high signal on T2-weighted MRI images; KT Adams, J Nambuba, P Herscovitch, SM Sadowski, they also often enhance intensely after gadolinium AT Fojo, I Buchmann, E Kebebew, K Pacak, unpublished injection on MRI. Flow signal voids in the tumor are observations). http://erc.endocrinology-journals.org q 2015 Society for Endocrinology Published by Bioscientifica Ltd. DOI: 10.1530/ERC-15-0175 Printed in Great Britain Downloaded from Bioscientifica.com at 09/27/2021 06:21:22PM via free access Thematic Review F Castinetti, K Pacak, PGL imaging 22:4 T137 D Taieb et al. Figure 1 4D MR angiography in a left tympanic PGL. (A) Selected dynamic images informative image extracted from 4D MR angiography (middle), fusion showing early arterial enhancement of the PGL (arrows). (B) Volumetric image with a CT scan for better evaluation of temporal bone extension interpolated fat-saturated (FATSAT) T1-weighted (VIBE) (left), an (right). 68Ga-DOTATATE has recently been accorded orphan chromaffin cells and regresses after birth by autophagy drug status by the US Food and Drug Administration, thereby (Schober et al. 2013). The OZ can also represent a site of Endocrine-Related Cancer increasing interest in and availability of the radiotracer. origin for PGLs
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