Generic placeholder image

Current Medical Imaging

Author(s): Luca Filippi*, Roberto Cianni, Orazio Schillaci and Oreste Bagni

DOI: 10.2174/1573405615666190114150038

DownloadDownload PDF Flyer Cite As
Molecular and Metabolic Imaging of Hepatic Neuroendocrine Tumors Following Radioembolization with 90Y-microspheres

Page: [545 - 552] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.

Keywords: Neuroendocrine tumors, radioembolization, 90Y-microspheres, PET, SPECT, FDG.

Graphical Abstract

[1]
Oronsky B, Ma PC, Morgensztern D, Carter CA. Nothing but NET: a review of neuroendocrine tumors and carcinomas. Neoplasia 2017; 19(12): 991-1002.
[http://dx.doi.org/10.1016/j.neo.2017.09.002] [PMID: 29091800]
[2]
Zhang M, Zhao P, Shi X, Zhao A, Zhang L, Zhou L. Clinicopathological features and prognosis of gastroenteropancreatic neuroendocrine neoplasms in a Chinese population: a large, retrospective single-centre study. BMC Endocr Disord 2017; 13; 17: 39.
[http://dx.doi.org/10.1186/s12902-017-0190-6]
[3]
Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9(1): 61-72.
[http://dx.doi.org/10.1016/S1470-2045(07)70410-2] [PMID: 18177818]
[4]
Helle KB, Corti A, Metz-Boutigue MH, Tota B. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 2007; 64(22): 2863-86.
[http://dx.doi.org/10.1007/s00018-007-7254-0] [PMID: 17717629]
[5]
Scalettar BA, Jacobs C, Fulwiler A, et al. Hindered submicron mobility and long-term storage of presynaptic dense-core granules revealed by single-particle tracking. Dev Neurobiol 2012; 72(9): 1181-95.
[http://dx.doi.org/10.1002/dneu.20984] [PMID: 21976424]
[6]
Chauhan A, Yu Q, Ray N, et al. Global burden of neuroendocrine tumors and changing incidence in Kentucky. Oncotarget 2018; 9(27): 19245-54.
[http://dx.doi.org/10.18632/oncotarget.24983] [PMID: 29721198]
[7]
Kvols LK, Buck M. Chemotherapy of endocrine malignancies: a review. Semin Oncol 1987; 14(3): 343-53.
[PMID: 2820064]
[8]
Wängberg B, Nilsson O, Johanson V, et al. Somatostatin receptors in the diagnosis and therapy of neuroendocrine tumor. Oncologist 1997; 2(1): 50-8.
[http://dx.doi.org/10.1634/theoncologist.2-1-50] [PMID: 10388029]
[9]
Kwekkeboom DJ, Krenning EP. Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am 2016; 30(1): 179-91.
[http://dx.doi.org/10.1016/j.hoc.2015.09.009] [PMID: 26614376]
[10]
Delbeke D, Graham MM. Joint guidance on peptide receptor radionuclide therapy in neuroendocrine tumors. J Nucl Med 2013; 54(5): 663.
[http://dx.doi.org/10.2967/jnumed.113.123190] [PMID: 23536220]
[11]
Hörsch D, Ezziddin S, Haug A, et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up. Eur J Cancer 2016; 58: 41-51.
[http://dx.doi.org/10.1016/j.ejca.2016.01.009] [PMID: 26943056]
[12]
Limouris GS, Karfis I, Chatzioannou A, et al. Super-selective hepatic arterial infusions as established technique (‘ARETAIEION’ Protocol) of [177Lu]DOTA-TATE in inoperable neuroendocrine liver metastases of gastro-entero-pancreatic (GEP) tumors. Q J Nucl Med Mol Imaging 2012; 56(6): 551-8.
[PMID: 23358409]
[13]
Cavalcoli F, Rausa E, Conte D, Nicolini AF, Massironi S. Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies? World J Gastroenterol 2017; 23(15): 2640-50.
[http://dx.doi.org/10.3748/wjg.v23.i15.2640] [PMID: 28487601]
[14]
Harring TR, Nguyen NTN, Goss JA, O’Mahony CA. Treatment of liver metastases in patients with neuroendocrine tumors: a comprehensive review. Int J Hepatol 2011; 2011 154541
[http://dx.doi.org/10.4061/2011/154541] [PMID: 22013537]
[15]
Joo I, Kim HC, Kim GM, Paeng JC. Imaging evaluation following 90Y Radioembolization of liver tumors: what radiologists should know. Korean J Radiol 2018; 19(2): 209-22.
[http://dx.doi.org/10.3348/kjr.2018.19.2.209] [PMID: 29520178]
[16]
Min SJ, Jang HJ, Kim JH. Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review. Oncotarget 2016; 7(19): 27848-54.
[http://dx.doi.org/10.18632/oncotarget.8425] [PMID: 27036043]
[17]
Velikyan I. Prospective of 68Ga-radiopharmaceutical development. Theranostics 2013; 4(1): 47-80.
[http://dx.doi.org/10.7150/thno.7447] [PMID: 24396515]
[18]
Kennedy A, Coldwell D, Sangro B, Wasan H, Salem R. Radioembolization for the treatment of liver tumors general principles. Am J Clin Oncol 2012; 35(1): 91-9.
[http://dx.doi.org/10.1097/COC.0b013e3181f47583] [PMID: 22363944]
[19]
Gates VL, Atassi B, Lewandowski RJ, et al. Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors. Future Oncol 2007; 3(1): 73-81.
[http://dx.doi.org/10.2217/14796694.3.1.73] [PMID: 17280504]
[20]
Filippi L, Schillaci O, Cianni R, Bagni O. Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma. Future Oncol 2018; 14(9): 809-18.
[http://dx.doi.org/10.2217/fon-2017-0443] [PMID: 29251517]
[21]
Wondergem M, Smits ML, Elschot M, et al. 99mTc-macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization. J Nucl Med 2013; 54(8): 1294-301.
[http://dx.doi.org/10.2967/jnumed.112.117614] [PMID: 23749996]
[22]
Braat AJ, Smits ML, Braat MN, et al. 90Y Hepatic Radioembolization: An Update on Current Practice and Recent Developments. J Nucl Med 2015; 56(7): 1079-87.
[http://dx.doi.org/10.2967/jnumed.115.157446] [PMID: 25952741]
[23]
Seidensticker R, Seidensticker M, Damm R, et al. Hepatic toxicity after radioembolization of the liver using (90)Y-microspheres: sequential lobar versus whole liver approach. Cardiovasc Intervent Radiol 2012; 35(5): 1109-18.
[http://dx.doi.org/10.1007/s00270-011-0295-7] [PMID: 22037709]
[24]
D’Arienzo M, Filippi L, Chiaramida P, et al. Absorbed dose to lesion and clinical outcome after liver radioembolization with 90Y microspheres: a case report of PET-based dosimetry. Ann Nucl Med 2013; 27(7): 676-80.
[http://dx.doi.org/10.1007/s12149-013-0726-4] [PMID: 23605058]
[25]
Cremonesi M, Chiesa C, Strigari L, et al. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol 2014; 4: 210.
[http://dx.doi.org/10.3389/fonc.2014.00210] [PMID: 25191640]
[26]
Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford) 2015; 17(1): 29-37.
[http://dx.doi.org/10.1111/hpb.12326] [PMID: 25186181]
[27]
Tovoli F, Renzulli M, Granito A, Golfieri R, Bolondi L. Radiologic criteria of response to systemic treatments for hepatocellular carcinoma. Hepat Oncol 2017; 4(4): 129-37.
[http://dx.doi.org/10.2217/hep-2017-0018] [PMID: 30191059]
[28]
Keppke AL, Salem R, Reddy D, et al. Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres. AJR Am J Roentgenol 2007; 188(3): 768-75.
[http://dx.doi.org/10.2214/AJR.06.0706] [PMID: 17312067]
[29]
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010; 30(1): 52-60.
[http://dx.doi.org/10.1055/s-0030-1247132] [PMID: 20175033]
[30]
Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. J Hepatol 2001; 35(3): 421-30.
[http://dx.doi.org/10.1016/S0168-8278(01)00130-1] [PMID: 11592607]
[31]
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009; 50(Suppl. 1): 122S-50S.
[http://dx.doi.org/10.2967/jnumed.108.057307] [PMID: 19403881]
[32]
O JH, Wahl RL. PERCIST in Perspective. Nucl Med Mol Imaging 2018; 52(1): 1-4.
[http://dx.doi.org/10.1007/s13139-017-0507-4] [PMID: 29391906]
[33]
Sabet A, Meyer C, Aouf A, et al. Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer. Eur J Nucl Med Mol Imaging 2015; 42(3): 370-6.
[http://dx.doi.org/10.1007/s00259-014-2935-z] [PMID: 25351506]
[34]
Filippi L, Di Costanzo GG, D’Agostini A, et al. Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis. Nucl Med Commun 2018; 39(9): 845-52.
[http://dx.doi.org/10.1097/MNM.0000000000000879] [PMID: 29901488]
[35]
Kitao T, Shiga T, Hirata K, et al. Volume-based parameters on FDG PET may predict the proliferative potential of soft-tissue sarcomas. Ann Nucl Med 2019; 33(1): 22-31.
[http://dx.doi.org/10.1007/s12149-018-1298-0] [PMID: 30196378]
[36]
Song YS, Lee WW, Chung JH, Park SY, Kim YK, Kim SE. Correlation between FDG uptake and glucose transporter type 1 expression in neuroendocrine tumors of the lung. Lung Cancer 2008; 61(1): 54-60.
[http://dx.doi.org/10.1016/j.lungcan.2007.11.012] [PMID: 18191496]
[37]
Reubi JC, Waser B, Khosla S, et al. In vitro and in vivo detection of somatostatin receptors in pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 1992; 74(5): 1082-9.
[PMID: 1349024]
[38]
Shah S, Purandare N, Agrawal A, Rangarajan V. A pictoral review on somatostatin receptor scintigraphy in neuroendocrine tumors: The role of multimodality imaging with SRS and GLUT receptor imaging with FDG PET-CT. Indian J Radiol Imaging 2012; 22(4): 267-75.
[http://dx.doi.org/10.4103/0971-3026.111478] [PMID: 23833417]
[39]
Krenning EP, Kwekkeboom DJ, Oei HY, et al. Somatostatin receptor scintigraphy in carcinoids, gastrinomas and Cushing’s syndrome. Digestion 1994; 55(Suppl. 3): 54-9.
[http://dx.doi.org/10.1159/000201202] [PMID: 7698538]
[40]
Krenning EP, Kwekkeboom DJ, Oei HY, et al. Somatostatin-receptor scintigraphy in gastroenteropancreatic tumors. An overview of European results. Ann N Y Acad Sci 1994; 733: 416-24.
[http://dx.doi.org/10.1111/j.1749-6632.1994.tb17291.x] [PMID: 7978890]
[41]
Filippi L, Valentini FB, Gossetti B, et al. Intraoperative gamma probe detection of head and neck paragangliomas with 111In-pentetreotide: a pilot study. Tumori 2005; 91(2): 173-6.
[http://dx.doi.org/10.1177/030089160509100213] [PMID: 15948547]
[42]
Schillaci O. Somatostatin receptor imaging in patients with neuroendocrine tumors: not only SPECT? J Nucl Med 2007; 48(4): 498-500.
[http://dx.doi.org/10.2967/jnumed.106.038653] [PMID: 17401084]
[43]
Skoura E, Michopoulou S, Mohmaduvesh M, et al. The Impact of 68Ga-DOTATATE PET/CT Imaging on management of patients with neuroendocrine tumors: experience from a national referral center in the United Kingdom. J Nucl Med 2016; 57(1): 34-40.
[http://dx.doi.org/10.2967/jnumed.115.166017] [PMID: 26471695]
[44]
Deppen SA, Blume J, Bobbey AJ, et al. 68Ga-DOTATATE compared with 111In-DTPA-octreotide and conventional imaging for pulmonary and Gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis. J Nucl Med 2016; 57(6): 872-8.
[http://dx.doi.org/10.2967/jnumed.115.165803] [PMID: 26769864]
[45]
Srirajaskanthan R, Kayani I, Quigley AM, Soh J, Caplin ME, Bomanji J. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy. J Nucl Med 2010; 51(6): 875-82.
[http://dx.doi.org/10.2967/jnumed.109.066134] [PMID: 20484441]
[46]
Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine 2012; 42(1): 80-7.
[http://dx.doi.org/10.1007/s12020-012-9631-1] [PMID: 22350660]
[47]
Sänger PW, Freesmeyer M. Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in patients with hepatic metastases of neuroendocrine tumors. Clin Nucl Med 2016; 41(6): 447-53.
[http://dx.doi.org/10.1097/RLU.0000000000001154] [PMID: 26859210]
[48]
Haug AR, Auernhammer CJ, Wängler B, et al. 68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med 2010; 51(9): 1349-56.
[http://dx.doi.org/10.2967/jnumed.110.075002] [PMID: 20720050]
[49]
Kratochwil C, Stefanova M, Mavriopoulou E, et al. SUV of 68GaDOTATOC-PET/CT predicts response probability of PRRT in neuroendocrine tumors. Mol Imaging Biol 2015; 17(3): 313-8.
[http://dx.doi.org/10.1007/s11307-014-0795-3] [PMID: 25319765]
[50]
Jia Z, Wang W. Yttrium-90 radioembolization for unresectable metastatic neuroendocrine liver tumor: A systematic review. Eur J Radiol 2018; 100: 23-9.
[http://dx.doi.org/10.1016/j.ejrad.2018.01.012] [PMID: 29496075]
[51]
Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 2008; 31(3): 271-9.
[http://dx.doi.org/10.1097/COC.0b013e31815e4557] [PMID: 18525307]
[52]
Ezziddin S, Meyer C, Kahancova S, et al. 90Y Radioembolization after radiation exposure from peptide receptor radionuclide therapy. J Nucl Med 2012; 53(11): 1663-9.
[http://dx.doi.org/10.2967/jnumed.112.107482] [PMID: 22988059]
[53]
Filippi L, Scopinaro F, Pelle G, et al. Molecular response assessed by (68)Ga-DOTANOC and survival after (90)Y microsphere therapy in patients with liver metastases from neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2016; 43(3): 432-40.
[http://dx.doi.org/10.1007/s00259-015-3178-3] [PMID: 26323577]
[54]
Has Simsek D, Kuyumcu S, Turkmen C, et al. Can complementary 68Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors? J Nucl Med 2014; 55(11): 1811-7.
[http://dx.doi.org/10.2967/jnumed.114.142224] [PMID: 25315243]
[55]
Kayani I, Bomanji JB, Groves A, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer 2008; 112(11): 2447-55.
[http://dx.doi.org/10.1002/cncr.23469] [PMID: 18383518]
[56]
Rinzivillo M, Partelli S, Prosperi D, et al. Clinical usefulness of 18F-Fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced Entero-Pancreatic neuroendocrine neoplasms. Oncologist 2018; 23(2): 186-92.
[http://dx.doi.org/10.1634/theoncologist.2017-0278] [PMID: 29118267]