Abstract
Neuroendocrine tumors (NETs) are rare tumors with a low incidence, characterized by a slow growth with often an indolent course. These tumors can arise in nearly all organs, with gastrointestinal and bronchopulmonary sites being the most common primary sites. The occurrence of primary neuroendocrine brain tumors is very rare, but metastases of NET to the brain are more common. The incidence of brain metastasis in patients with NET is approximately 1.5–5% with a median age of diagnosis of 60 years. Detection of NET brain metastases occurs with a median of 1.5 years after diagnosis of primary NET with a likely underdiagnosis. Brain metastases most commonly develop in patients with bronchopulmonary NET. Brain metastases grow globoid with a microglial boundary and are often surrounded by vasogenic edema. Metastatic brain lesions are made up of a subgroup of cells with a different biological behavior compared to the primary NET and other metastases which can be explained by the difficulties these cells have to face before being able to successfully grow within the brain. These patients suffer from a more aggressive NET behavior, and in many patients, carcinoid syndrome is also present. Clinical presentation is mostly characterized by headaches, personality changes, and gait disturbances.
According to the European Neuroendocrine Tumor Society (ENETS) consensus guidelines, MRI is the preferred modality for detection of NET brain metastases. However, PET has gained a very important role in the staging of NET, and it is likely that PET will become very helpful for the detection of neuroendocrine brain tumors and metastases. Several tracers are available at this moment, of which somatostatin receptor PET and 18F-DOPA PET seem the most promising at this moment. Due to the high background uptake in the brain and the relatively low glucose metabolism in NET cells, the indication of 18F-FDG PET seems very limited for the detection of neuroendocrine brain tumors.
However, due to the rarity of NET overall and thus especially for NET brain metastases, data on these tumors is limited, and additional research is warranted.
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References
Adams S, Baum R, Rink T, Schumm-Drager PM, Usadel KH, Hor G (1998) Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 25(1):79–83
Batson OV (1940) The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112(1):138–149
Belhocine T, Foidart J, Rigo P, Najjar F, Thiry A, Quatresooz P, Hustinx R (2002) Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun 23(8):727–734
Bjurling P, Watanabe Y, Tokushige M, Oda T, Långström B (1989) Syntheses of β-11C-labelled L-tryptophan and 5-hydroxy-L-tryptophan using a multi-enzymatic reaction route. J Chem Soc Perkin Trans 1(7):1331–1334
Carreras C, Kulkarni HR, Baum RP (2013) Rare metastases detected by (68)Ga-somatostatin receptor PET/CT in patients with neuroendocrine tumors. Recent Results Cancer Res 194:379–384. https://doi.org/10.1007/978-3-642-27994-2_20
Chen W, Silverman DH, Delaloye S, Czernin J, Kamdar N, Pope W et al (2006) 18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. J Nucl Med 47(6):904–911
Cho KH, Hall WA, Gerbi BJ, Higgins PD, Bohen M, Clark HB (1998) Patient selection criteria for the treatment of brain metastases with stereotactic radiosurgery. J Neurooncol 40(1):73–86
Doddoli C, Barlesi F, Chetaille B, Garbe L, Thomas P, Giudicelli R, Fuentes P (2004) Large cell neuroendocrine carcinoma of the lung: an aggressive disease potentially treatable with surgery. Ann Thorac Surg 77(4):1168–1172. https://doi.org/10.1016/j.athoracsur.2003.09.049
Garnett ES, Firnau G, Nahmias C (1983) Dopamine visualized in the basal ganglia of living man. Nature 305(5930):137–138
Godwin JD II (1975) Carcinoid tumors. An analysis of 2,837 cases. Cancer 36(2):560–569
Granberg D, Wilander E, Oberg K, Skogseid B (2000) Prognostic markers in patients with typical bronchial carcinoid tumors. J Clin Endocrinol Metab 85(9):3425–3430
He BP, Wang JJ, Zhang X, Wu Y, Wang M, Bay BH, Chang AY (2006) Differential reactions of microglia to brain metastasis of lung cancer. Mol Med 12(7–8):161–170. https://doi.org/10.2119/2006-00033.He
Heiss WD, Wienhard K, Wagner R, Lanfermann H, Thiel A, Herholz K, Pietrzyk U (1996) F-Dopa as an amino acid tracer to detect brain tumors. J Nucl Med 37(7):1180–1182
Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker DW, Doll J et al (2001) PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 42(7):1053–1056
Hlatky R, Suki D, Sawaya R (2004) Carcinoid metastasis to the brain. Cancer 101(11):2605–2613. https://doi.org/10.1002/cncr.20659
Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H et al (2001) Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology 220(2):373–380
Hofland LJ, Lamberts SW (2003) The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 24(1):28–47
Hofmann M, Maecke H, Borner R, Weckesser E, Schoffski P, Oei L et al (2001) Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data. Eur J Nucl Med 28(12):1751–1757. https://doi.org/10.1007/s002590100639
Jager PL, Chirakal R, Marriott CJ, Brouwers AH, Koopmans KP, Gulenchyn KY (2008) 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications. J Nucl Med 49(4):573–586. https://doi.org/10.2967/jnumed.107.045708
Khan IU, Beck-Sickinger AG (2008) Targeted tumor diagnosis and therapy with peptide hormones as radiopharmaceuticals. Anti Cancer Agents Med Chem 8(2):186–199
Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360(9334):683–689. https://doi.org/10.1016/S0140-6736(02)09838-0
Kloppel G, Heitz PU, Capella C, Solcia E (1996) Pathology and nomenclature of human gastrointestinal neuroendocrine (carcinoid) tumors and related lesions. World J Surg 20(2):132–141
Koopmans KP, Neels OC, Kema IP, Elsinga PH, Sluiter WJ, Vanghillewe K et al (2008) Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 26(9):1489–1495. https://doi.org/10.1200/JCO.2007.15.1126
Koopmans KP, Neels ON, Kema IP, Elsinga PH, Links TP, de Vries EG, Jager PL (2009) Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results. Crit Rev Oncol Hematol 71(3):199–213. https://doi.org/10.1016/j.critrevonc.2009.02.009
Krenning EP, Bakker WH, Kooij PP, Breeman WA, Oei HY, de Jong M et al (1992) Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 33(5):652–658
Krug S, Teupe F, Michl P, Gress TM, Rinke A (2019) Brain metastases in patients with neuroendocrine neoplasms: risk factors and outcome. BMC Cancer 19(1):362. https://doi.org/10.1186/s12885-019-5559-7
Kruger S, Mottaghy FM, Buck AK, Maschke S, Kley H, Frechen D et al (2011) Brain metastasis in lung cancer. Comparison of cerebral MRI and 18F-FDG-PET/CT for diagnosis in the initial staging. Nuklearmedizin 50(3):101–106. https://doi.org/10.3413/Nukmed-0338-10-07
Lamberts SW, Reubi JC, Krenning EP (1993) Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors. Acta Oncol 32(2):167–170
Lemaire C, Damhaut P, Plenevaux A, Comar D (1994) Enantioselective synthesis of 6-[fluorine-18]-fluoro-L-dopa from no-carrier-added fluorine-18-fluoride. J Nucl Med 35(12):1996–2002
Lepage C, Bouvier AM, Faivre J (2013) Endocrine tumours: epidemiology of malignant digestive neuroendocrine tumours. Eur J Endocrinol 168(4):R77–R83. https://doi.org/10.1530/EJE-12-0418
Maiuri F, Cappabianca P, Del Basso De Caro M, Esposito F (2004) Single brain metastases of carcinoid tumors. J Neurooncol 66(3):327–332
Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97(4):934–959. https://doi.org/10.1002/cncr.11105
Nakamura Y, Shimokawa S, Ishibe R, Ikee T, Taira A (2001) Pulmonary carcinoid found in a patient who presented with initial symptoms of brain metastasis: report of a case. Surg Today 31(6):510–512
Neels OC, Jager PL, Koopmans KP, Eriks E, de Vries EGE, Kema IP, Elsinga PL (2006) Development of a reliable remote-controlled synthesis of β-[11C]-5-hydroxy-L-tryptophan on a Zymark robotic system. J Label Compd Radiopharm 49:889–895
Pasquali C, Rubello D, Sperti C, Gasparoni P, Liessi G, Chierichetti F et al (1998) Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg 22(6):588–592
Patchell RA, Posner JB (1986) Neurologic complications of carcinoid. Neurology 36(6):745–749
Pavel M, Grossman A, Arnold R, Perren A, Kaltsas G, Steinmuller T et al (2010) ENETS consensus guidelines for the management of brain, cardiac and ovarian metastases from neuroendocrine tumors. Neuroendocrinology 91(4):326–332. https://doi.org/10.1159/000287277
Porter DG, Chakrabarty A, McEvoy A, Bradford R (2000) Intracranial carcinoid without evidence of extracranial disease. Neuropathol Appl Neurobiol 26(3):298–300
Reubi JC (1995) Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J Nucl Med 36(10):1825–1835
Schnirer II, Yao JC, Ajani JA (2003) Carcinoid—a comprehensive review. Acta Oncol 42(7):672–692
Soga J (2003) Carcinoids and their variant endocrinomas. An analysis of 11842 reported cases. J Exp Clin Cancer Res 22(4):517–530
Sul J, Posner JB (2007) Brain metastases: epidemiology and pathophysiology. Cancer Treat Res 136:1–21
Weckbecker G, Lewis I, Albert R, Schmid HA, Hoyer D, Bruns C (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2(12):999–1017. https://doi.org/10.1038/nrd1255
Yamagi, L.Y.I., Wagner, J., Funari M.B.G. (2017)68Ga-DOTATATE PET/CT in nonneuroendocrine tumors: a pictorial essay. Clin Nucl Med 42(6):e313-e316
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Koopmans, K.P., Brouwers, A.H. (2021). Imaging Brain Metastases of Neuroendocrine Tumors. In: Dierckx, R.A.J.O., Otte, A., de Vries, E.F.J., van Waarde, A., Leenders, K.L. (eds) PET and SPECT in Neurology. Springer, Cham. https://doi.org/10.1007/978-3-030-53168-3_42
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