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20-02-2017 | Neuroendocrine tumors | Article

Radionuclide Therapy for Neuroendocrine Tumors

Journal: Current Oncology Reports

Authors: Mauro Cives, Jonathan Strosberg

Publisher: Springer US

Abstract

Peptide receptor radionuclide therapy (PRRT) is a form of systemic radiotherapy that allows targeted delivery of radionuclides to tumor cells expressing high levels of somatostatin receptors. The two radiopeptides most commonly used for PRRT, 90Y-DOTATOC and 177Lu-DOTATATE, have been successfully employed for more than a decade for the treatment of advanced neuroendocrine tumors (NETs). Recently, the phase III, randomized NETTER-1 trial has compared 177Lu-DOTATATE versus high-dose octreotide LAR in patients with progressive, metastatic midgut NETs, demonstrating exceptional tolerability and efficacy. This review summarizes recent developments in the field of radionuclide therapy for gastroenteropancreatic and lung NETs and considers possible strategies to further enhance its clinical efficacy.
Literature
1.
Cives M, Strosberg J. An update on gastroenteropancreatic neuroendocrine tumors. Oncology (Williston Park). 2014;28(9):749–56,758.
2.
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72.CrossRefPubMed
3.
Cives M, Soares HP, Strosberg J. Will clinical heterogeneity of neuroendocrine tumors impact their management in the future? Lessons from recent trials. Curr Opin Oncol. 2016;28(4):359–66.CrossRefPubMed
4.
Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61–72.CrossRefPubMed
5.
Kim SJ, Kim JW, Han SW, Oh DY, Lee SH, Kim DW, Im SA, Kim TY, Seog Heo D, Bang YJ. Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy. BMC Cancer. 2010;10:448.CrossRefPubMedPubMedCentral
6.
Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, Oei HY, de Jong M, Visser TJ, Reijs AE, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci. 1994;733:496–506.CrossRefPubMed
7.
•• Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E. NETTER-1 Trial Investigators. N Engl J Med. 2017;376(2):125–135. doi:10.​1056/​NEJMoa1607427. This is the first phase III clinical trial to provide high-level evidence of the efficacy and tolerability of PRRT in patients with progressive midgut NET .
8.
Papotti M, Bongiovanni M, Volante M, Allı’a E, Landolfi S, Helboe L, Schindler M, Cole SL, Bussolati G. Expression of somatostatin receptor types 1–5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch. 2002;440(5):461–75.CrossRefPubMed
9.
Kaemmerer D, Specht E, Sa¨nger J, Wirtz RM, Sayeg M, Schulz S, Lupp A. Somatostatin receptors in bronchopulmonary neuroendocrine neoplasms: new diagnostic, prognostic, and therapeutic markers. J Clin Endocrinol Metab 2015;100(3):831–840.
10.
Modlin IM, Pavel M, Kidd M, Gustafsson BI. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31(2):169–88.PubMed
11.
Capello A, Krenning EP, Breeman WA, Bernard BF, de Jong M. Peptide receptor radionuclide therapy in vitro using [111In-DTPA0]octreotide. J Nucl Med. 2003;44(1):98–104.PubMed
12.
Pool SE, Krenning EP, Koning GA, van Eijck CH, Teunissen JJ, Kam B, Valkema R, Kwekkeboom DJ, de Jong M. Preclinical and clinical studies of peptide receptor radionuclide therapy. Semin Nucl Med. 2010;40(3):209–18.CrossRefPubMed
13.
Van Essen M, Krenning EP, De Jong M, Valkema R, Kwekkeboom DJ. Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol. 2007;46(6):723–34.CrossRefPubMed
14.
Kwekkeboom DJ, Kam BL, van Essen M, Teunissen JJ, van Eijck CH, Valkema R, de Jong M, de Herder WW, Krenning EP. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer. 2010;17(1):R53–73.CrossRefPubMed
15.
Kratochwil C, Stefanova M, Mavriopoulou E, Holland-Letz T, Dimitrakopoulou-Strauss A, Afshar-Oromieh A, Mier W, Haberkorn U, Giesel FL. SUV of [68Ga]DOTATOC-PET/CT predicts response probability of PRRT in neuroendocrine tumors. Mol Imaging Biol. 2015;17(3):313–8.CrossRefPubMed
16.
Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, Esser JP, Kam BL, Krenning EP. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005;23(12):2754–62.CrossRefPubMed
17.
Ezziddin S, Attassi M, Yong-Hing CJ, Ahmadzadehfar H, Willinek W, Grünwald F, Guhlke S, Biersack HJ, Sabet A. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med. 2014;55(2):183–90.CrossRefPubMed
18.
Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled somatostatin analogue therapy of gastroenteropancreatic cancer. Semin Nucl Med. 2016;46(3):225–38.CrossRefPubMed
19.
Valkema R, De Jong M, Bakker WH, Breeman WA, Kooij PP, Lugtenburg PJ, De Jong FH, Christiansen A, Kam BL, De Herder WW, Stridsberg M, Lindemans J, Ensing G, Krenning EP. Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Semin Nucl Med. 2002;32(2):110–22.CrossRefPubMed
20.
Anthony LB, Woltering EA, Espenan GD, Cronin MD, Maloney TJ, McCarthy KE. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med. 2002;32(2):123–32.CrossRefPubMed
21.
Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, Haldemann A, Mueller-Brand J. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002;43(5):610–6.PubMed
22.
Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, Kwekkeboom DJ, Bouterfa H, Krenning EP. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med. 2006;36(2):147–56.CrossRefPubMed
23.
Bushnell Jr DL, O'Dorisio TM, O'Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu JL, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, Kacena KA, LaFrance N, Pauwels SA. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28(10):1652–9.CrossRefPubMedPubMedCentral
24.
Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Mäcke HR, Rochlitz C, Müller-Brand J, Walter MA. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29(17):2416–23.CrossRefPubMed
25.
Kwekkeboom DJ, Krenning EP. Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am. 2016;30(1):179–91.CrossRefPubMed
26.
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, Feelders RA, van Eijck CH, de Jong M, Srinivasan A, Erion JL, Krenning EP. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003;30(3):417–22.CrossRefPubMedPubMedCentral
27.
Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QK, Maecke HR, Müller-Brand J, Rochlitz C, Briel M, Schindler C, Walter MA. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41(2):214–22.CrossRefPubMed
28.
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26(13):2124–30.CrossRefPubMed
29.
Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, Bartolomei M, Lombardo D, Ferrari ME, Sansovini M, Chinol M, Paganelli G. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011;38(12):2125–35.CrossRefPubMed
30.
Ezziddin S, Khalaf F, Vanezi M, Haslerud T, Mayer K, Al Zreiqat A, Willinek W, Biersack HJ, Sabet A. Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41(5):925–33.CrossRefPubMed
31.
Kim SJ, Pak K, Koo PJ, Kwak JJ, Chang S. The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging. 2015;42(13):1964–70.CrossRefPubMed
32.
Khan S, Krenning EP, van Essen M, Kam BL, Teunissen JJ, Kwekkeboom DJ. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med. 2011;52(9):1361–8.CrossRefPubMed
33.
Sabet A, Dautzenberg K, Haslerud T, Aouf A, Sabet A, Simon B, Mayer K, Biersack HJ, Ezziddin S. Specific efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in advanced neuroendocrine tumours of the small intestine. Eur J Nucl Med Mol Imaging. 2015;42(8):1238–46.CrossRefPubMed
34.
Paganelli G, Sansovini M, Ambrosetti A, Severi S, Monti M, Scarpi E, Donati C, Ianniello A, Matteucci F, Amadori D. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. Eur J Nucl Med Mol Imaging. 2014;41(10):1845–51.CrossRefPubMed
35.
Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R, PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol. 2009;27(28):4656–63.CrossRefPubMed
36.
Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371(3):224–233.
37.
Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Delle Fave G, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME RAD001 in advanced neuroendocrine tumours, fourth trial (RADIANT-4) study group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016; 387(10022):968–977.
38.
Diakatou E, Alexandraki KI, Tsolakis AV, Kontogeorgos G, Chatzellis E, Leonti A, Kaltsas GA. Somatostatin and dopamine receptor expression in neuroendocrine neoplasms: correlation of immunohistochemical findings with somatostatin receptor scintigraphy visual scores. Clin Endocrinol. 2015;83(3):420–8.CrossRef
39.
Ianniello A, Sansovini M, Severi S, Nicolini S, Grana CM, Massri K, Bongiovanni A, Antonuzzo L, Di Iorio V, Sarnelli A, Caroli P, Monti M, Scarpi E, Paganelli G. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET. Eur J Nucl Med Mol Imaging. 2016;43(6):1040–6.CrossRefPubMed
40.
Mariniello A, Bodei L, Tinelli C, Baio SM, Gilardi L, Colandrea M, Papi S, Valmadre G, Fazio N, Galetta D, Paganelli G, Grana CM. Long-term results of PRRT in advanced bronchopulmonary carcinoid. Eur J Nucl Med Mol Imaging. 2016;43(3):441–52.CrossRefPubMed
41.
Forrer F, Uusijärvi H, Storch D, Maecke HR, Mueller-Brand J. Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med. 2005;46(8):1310–6.PubMed
42.
Van Essen M, Krenning EP, Kam BL, de Herder WW, Feelders RA, Kwekkeboom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010;51(3):383–90.CrossRefPubMed
43.
Severi S, Sansovini M, Ianniello A, Bodei L, Nicolini S, Ibrahim T, Di Iorio V, D'Errico V, Caroli P, Monti M, Paganelli G. Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC. Eur J Nucl Med Mol Imaging. 2015;42(13):1955–63.CrossRefPubMed
44.
van Essen M, Krenning EP, Kam BL, de Herder WW, van Aken MO, Kwekkeboom DJ. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35(4):743–8.CrossRefPubMedPubMedCentral
45.
Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38(2):302–11.CrossRefPubMed
46.
Kong G, Thompson M, Collins M, Herschtal A, Hofman MS, Johnston V, Eu P, Michael M, Hicks RJ. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT). Eur J Nucl Med Mol Imaging. 2014;41(10):1831–44.CrossRefPubMedPubMedCentral
47.
Claringbold PG, Price RA, Turner JH. Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother Radiopharm. 2012;27(9):561–9.CrossRefPubMed
48.
Claringbold PG, Turner JH. Pancreatic neuroendocrine tumor control: durable objective response to combination 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy. Neuroendocrinology. 2016;103(5):432–9.CrossRefPubMed
49.
Claringbold PG, Turner JH. Neuroendocrine tumor therapy with lutetium-177-octreotate and everolimus (NETTLE): a phase I study. Cancer Biother Radiopharm. 2015;30(6):261–9.CrossRefPubMed
50.
Seregni E, Maccauro M, Chiesa C, Mariani L, Pascali C, Mazzaferro V, De Braud F, Buzzoni R, Milione M, Lorenzoni A, Bogni A, Coliva A, Lo Vullo S, Bombardieri E. Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy. Eur J Nucl Med Mol Imaging. 2014;41(2):223–30.CrossRefPubMed
51.
Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, Mikołajczak R, Sowa-Staszczak A, Pawlak D. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38(10):1788–97.CrossRefPubMedPubMedCentral
52.
Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, Ng QK, Mäcke HR, Müller-Brand J, Rochlitz C, Briel M, Walter MA. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol. 2012;30(10):1100–6.CrossRefPubMed
53.
de Keizer B, van Aken MO, Feelders RA, de Herder WW, Kam BL, van Essen M, Krenning EP, Kwekkeboom DJ. Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2008;35(4):749–55.CrossRefPubMedPubMedCentral
54.
Rolleman EJ, Valkema R, de Jong M, Kooij PP, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging. 2003;30(1):9–15.CrossRefPubMed
55.
Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, Caracciolo M, Mäcke HR, Chinol M, Paganelli G. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging. 2003;30(2):207–16.CrossRefPubMed
56.
Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, Barone R, Walrand S, Kooij PP, Bakker WH, Lasher J, Krenning EP. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0),Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med. 2005;46(Suppl 1):83S–91S.PubMed
57.
Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, Baio SM, Sansovini M, Paganelli G. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008;35(10):1847–56.CrossRefPubMed
58.
• Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, Lepensky C, Kwekkeboom DJ, Baum RP, Krenning EP, Modlin IM. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015;42(1):5–19. This work provides evidence that PRRT has a favorable long-term tolerability profile in patients with NETs.CrossRefPubMed
59.
• Kesavan M, Turner JH. Myelotoxicity of peptide receptor radionuclide therapy of neuroendocrine tumors: a decade of experience. Cancer Biother Radiopharm. 2016;31(6):189–98. This systematic review of the literature demonstrates that PRRT is associated with a very low risk of myelodysplasia and acute leukemia . CrossRefPubMed
60.
Kaemmerer D, Prasad V, Daffner W, Hörsch D, Klöppel G, Hommann M, Baum RP. Neoadjuvant peptide receptor radionuclide therapy for an inoperable neuroendocrine pancreatic tumor. World J Gastroenterol. 2009;15(46):5867–70.CrossRefPubMedPubMedCentral
61.
Barber TW, Hofman MS, Thomson BN, Hicks RJ. The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable. Eur J Surg Oncol. 2012;38(1):64–71.CrossRefPubMed
62.
Ezziddin S, Lauschke H, Schaefers M, Meyer C, van Essen M, Biersack HJ, Kwekkeboom DJ, Ahmadzadehfar H. Neoadjuvant downsizing by internal radiation: a case for preoperative peptide receptor radionuclide therapy in patients with pancreatic neuroendocrine tumors. Clin Nucl Med. 2012;37(1):102–4.CrossRefPubMed
63.
Sowa-Staszczak A, Pach D, Chrzan R, Trofimiuk M, Stefańska A, Tomaszuk M, Kołodziej M, Mikołajczak R, Pawlak D, Hubalewska-Dydejczyk A. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging. 2011;38(9):1669–74.CrossRefPubMedPubMedCentral
64.
van Vliet EI, van Eijck CH, de Krijger RR, Nieveen van Dijkum EJ, Teunissen JJ, Kam BL, de Herder WW, Feelders RA, Bonsing BA, Brabander T, Krenning EP, Kwekkeboom DJ. Neoadjuvant treatment of nonfunctioning pancreatic neuroendocrine tumors with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med. 2015;56(11):1647–53.CrossRefPubMed
65.
• Kratochwil C, Giesel FL, Bruchertseifer F, Mier W, Apostolidis C, Boll R, Murphy K, Haberkorn U, Morgenstern A. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience. Eur J Nucl Med Mol Imaging. 2014;41(11):2106–19. This is the first study to demonstrate that PRRT with 213 Bi is feasible and effective in patients with NETs. CrossRefPubMedPubMedCentral
66.
Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, Erchegyi J, Rivier J, Mäcke HR, Reubi JC. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci U S A. 2006;103(44):16436–41.CrossRefPubMedPubMedCentral
67.
• Wild D, Fani M, Fischer R, Del Pozzo L, Kaul F, Krebs S, Fischer R, Rivier JE, Reubi JC, Maecke HR, Weber WA. Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: a pilot study. J Nucl Med. 2014;55(8):1248–52. This is the first work to report the safety and efficacy of a radiolabeled somatostatin antagonist in patients with NETs. CrossRefPubMed
68.
Nonnekens J, van Kranenburg M, Beerens CE, Suker M, Doukas M, van Eijck CH, de Jong M, van Gent DC. Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib. Theranostics. 2016;6(11):1821–32.CrossRefPubMedPubMedCentral
69.
Wu Y, Pfeifer AK, Myschetzky R, Garbyal RS, Rasmussen P, Knigge U, Bzorek M, Kristensen MH, Kjaer A. Induction of anti-tumor immune responses by peptide receptor radionuclide therapy with (177)Lu-DOTATATE in a murine model of a human neuroendocrine tumor. Diagnostics (Basel). 2013;3(4):344–55.CrossRef
70.
Druce MR, Lewington V, Grossman AB. Targeted radionuclide therapy for neuroendocrine tumours: principles and application. Neuroendocrinology. 2010;91(1):1–15.CrossRefPubMed
71.
de Kruijff RM, Wolterbeek HT, Denkova AG. A critical review of alpha radionuclide therapy—how to deal with recoiling daughters? Pharmaceuticals (Basel). 2015;8(2):321–36.CrossRef