Download PDF
Digestive Disease Interventions 2019; 03(01): 071-080
DOI: 10.1055/s-0038-1676064
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Peptide Receptor Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

Ghassan El-Haddad
1   Section Head of Radionuclide Therapy Program, Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
› Author Affiliations
Further Information

Publication History

19 September 2018

09 October 2018

Publication Date:
17 January 2019 (online)

Also available at
    Permissions and Reprints

Abstract

Peptide receptor radionuclide therapy (PRRT), a targeted form of systemic radiotherapy allowing the delivery of radionuclides directly to tumor cells, has been used for more than three decades in the treatment of advanced neuroendocrine tumors (NETs) exhibiting high levels of somatostatin receptors. Recently, 177Lu-DOTATATE, a radiolabeled somatostatin analog, was approved by the US Food and Drug administration for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. Early phase I and II studies have shown the benefits of PRRT, but it was the NETTER-1 trial (a large-scale randomized multicenter trial for progressive well-differentiated advanced or metastatic somatostatin receptor-positive midgut carcinoid tumors) that provided high-level evidence of improved overall response rate, and progression-free survival compared with long-acting octreotide. In this article, we will discuss the evolution, clinical applications, and implementation of PRRT, as well as potential future strategies to enhance its clinical efficacy in the treatment of GEP-NETs.

Keywords

peptide receptor radionuclide therapy - NETTER-1 - neuroendocrine tumor - pancreas - carcinoid
 

  • References

  • 1 Alexandraki KI, Kaltsas G. Gastroenteropancreatic neuroendocrine tumors: new insights in the diagnosis and therapy. Endocrine 2012; 41 (01) 40-52
    CrossrefPubMedGoogle Scholar
  • 2 Dasari A, Shen C, Halperin D. , et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 2017; 3 (10) 1335-1342
    CrossrefPubMedGoogle Scholar
  • 3 Strosberg J, El-Haddad G, Wolin E. , et al; NETTER-1 Trial Investigators Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376 (02) 125-135
    CrossrefPubMedGoogle Scholar
  • 4 Reubi JC, Schär J-C, Waser B. , et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000; 27 (03) 273-282
    CrossrefPubMedGoogle Scholar
  • 5 Hofland LJ, van der Hoek J, Feelders R, van der Lely AJ, de Herder W, Lamberts SW. Pre-clinical and clinical experiences with novel somatostatin ligands: advantages, disadvantages and new prospects. J Endocrinol Invest 2005; 28 (11) , Suppl International ): 36-42
    PubMedGoogle Scholar
  • 6 Srirajaskanthan R, Watkins J, Marelli L, Khan K, Caplin ME. Expression of somatostatin and dopamine 2 receptors in neuroendocrine tumours and the potential role for new biotherapies. Neuroendocrinology 2009; 89 (03) 308-314
    CrossrefPubMedGoogle Scholar
  • 7 Reubi JC, Mäcke HR, Krenning EP. Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med 2005; 46 (Suppl (Suppl. 01) 67S-75S
    PubMedGoogle Scholar
  • 8 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 (02) 123-132
    CrossrefPubMedGoogle Scholar
  • 9 Valkema R, De Jong M, Bakker WH. , et al. Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Semin Nucl Med 2002; 32 (02) 110-122
    CrossrefPubMedGoogle Scholar
  • 10 Krenning EP, de Jong M, Kooij PP. , et al. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol 1999; 10 (Suppl (Suppl. 02) S23-S29
    CrossrefPubMedGoogle Scholar
  • 11 Valkema R, Pauwels S, Kvols LK. , et al. 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 (02) 147-156
    CrossrefPubMedGoogle Scholar
  • 12 Kwekkeboom DJ, de Herder WW, Kam BL. , et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26 (13) 2124-2130
    CrossrefPubMedGoogle Scholar
  • 13 Kam BL, Teunissen JJ, Krenning EP. , et al. Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39 (Suppl (Suppl. 01) S103-S112
    CrossrefPubMedGoogle Scholar
  • 14 Bergsma H, Konijnenberg MW, van der Zwan WA. , et al. Nephrotoxicity after PRRT with (177)Lu-DOTA-octreotate. Eur J Nucl Med Mol Imaging 2016; 43 (10) 1802-1811
    CrossrefPubMedGoogle Scholar
  • 15 Valkema R, Pauwels SA, Kvols LK. , et al. 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 (Suppl. 01) 83S-91S
    PubMedGoogle Scholar
  • 16 Bodei L, Mueller-Brand J, Baum RP. , et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013; 40 (05) 800-816
    CrossrefPubMedGoogle Scholar
  • 17 Imhof A, Brunner P, Marincek N. , et al. 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) 2416-2423
    CrossrefPubMedGoogle Scholar
  • 18 Melis M, Krenning EP, Bernard BF, Barone R, Visser TJ, de Jong M. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues. Eur J Nucl Med Mol Imaging 2005; 32 (10) 1136-1143
    CrossrefPubMedGoogle Scholar
  • 19 Jamar F, Barone R, Mathieu I. , et al. 86Y-DOTA0)-D-Phe1-Tyr3-octreotide (SMT487)--a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003; 30 (04) 510-518
    CrossrefPubMedGoogle Scholar
  • 20 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 (01) 9-15
    CrossrefPubMedGoogle Scholar
  • 21 Cremonesi M, Ferrari M, Di Dia A. , et al. Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy. Q J Nucl Med Mol Imaging 2011; 55 (02) 155-167
    PubMedGoogle Scholar
  • 22 Cwikla JB, Sankowski A, Seklecka N. , et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol 2010; 21 (04) 787-794
    CrossrefPubMedGoogle Scholar
  • 23 Pfeifer AK, Gregersen T, Grønbæk H. , et al. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland. Neuroendocrinology 2011; 93 (03) 189-196
    CrossrefPubMedGoogle Scholar
  • 24 Savelli G, Bertagna F, Franco F. , et al. Final results of a phase 2A study for the treatment of metastatic neuroendocrine tumors with a fixed activity of 90Y-DOTA-D-Phe1-Tyr3 octreotide. Cancer 2012; 118 (11) 2915-2924
    CrossrefPubMedGoogle Scholar
  • 25 Delpassand ES, Samarghandi A, Zamanian S. , et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Pancreas 2014; 43 (04) 518-525
    CrossrefPubMedGoogle Scholar
  • 26 Ezziddin S, Khalaf F, Vanezi M. , et al. 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 (05) 925-933
    CrossrefPubMedGoogle Scholar
  • 27 Sabet A, Dautzenberg K, Haslerud T. , et al. 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 (08) 1238-1246
    CrossrefPubMedGoogle Scholar
  • 28 Strosberg J, Wolin E, Chasen B. , et al; NETTER-1 Study Group Health-related quality of life in patients with progressive midgut neuroendocrine tumors treated with 177Lu-Dotatate in the phase III NETTER-1 trial. J Clin Oncol 2018; 36 (25) 2578-2584
    CrossrefPubMedGoogle Scholar
  • 29 Brabander T, van der Zwan WA, Teunissen JJM. , et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res 2017; 23 (16) 4617-4624
    CrossrefPubMedGoogle Scholar
  • 30 Food and Drug Administration. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208700s000lbl.pdf . Accessed 01/26/ 2018
    PubMed
  • 31 Bodei L, Kidd M, Paganelli G. , et al. 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 (01) 5-19
    CrossrefPubMedGoogle Scholar
  • 32 Hicks RJ, Kwekkeboom DJ, Krenning E. , et al; Antibes Consensus Conference participants ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabeled somatostatin analogues. Neuroendocrinology 2017; 105 (03) 295-309
    CrossrefPubMedGoogle Scholar
  • 33 Kwekkeboom DJ, Kam BL, van Essen M. , et al. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer 2010; 17 (01) R53-R73
    CrossrefPubMedGoogle Scholar
  • 34 Brabander T, van der Zwan WA, Teunissen JJM. , et al. Pitfalls in the response evaluation after peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate. Endocr Relat Cancer 2017; 24 (05) 243-251
    CrossrefPubMedGoogle Scholar
  • 35 Kwekkeboom DJ, Teunissen JJ, Bakker WH. , et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005; 23 (12) 2754-2762
    CrossrefPubMedGoogle Scholar
  • 36 Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics 2015; 35 (02) 500-516
    CrossrefPubMedGoogle Scholar
  • 37 Kratochwil C, Stefanova M, Mavriopoulou E. , et al. SUV of [68Ga]DOTATOC-PET/CT predicts response probability of PRRT in neuroendocrine tumors. Mol Imaging Biol 2015; 17 (03) 313-318
    CrossrefPubMedGoogle Scholar
  • 38 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 (06) 872-878
    CrossrefPubMedGoogle Scholar
  • 39 Buchmann I, Henze M, Engelbrecht S. , et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2007; 34 (10) 1617-1626
    CrossrefPubMedGoogle Scholar
  • 40 Etchebehere EC, de Oliveira Santos A, Gumz B. , et al. 68Ga-DOTATATE PET/CT, 99mTc-HYNIC-octreotide SPECT/CT, and whole-body MR imaging in detection of neuroendocrine tumors: a prospective trial. J Nucl Med 2014; 55 (10) 1598-1604
    CrossrefPubMedGoogle Scholar
  • 41 Hope TA, Bergsland EK, Bozkurt MF. , et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med 2018; 59 (01) 66-74
    CrossrefPubMedGoogle Scholar
  • 42 Ezziddin S, Attassi M, Yong-Hing CJ. , et al. 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 (02) 183-190
    CrossrefPubMedGoogle Scholar
  • 43 Yao JC, Eisner MP, Leary C. , et al. Population-based study of islet cell carcinoma. Ann Surg Oncol 2007; 14 (12) 3492-3500
    CrossrefPubMedGoogle Scholar
  • 44 Janson ET, Holmberg L, Stridsberg M. , et al. Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 1997; 8 (07) 685-690
    CrossrefPubMedGoogle Scholar
  • 45 Pavel M, Baudin E, Couvelard A. , et al; Barcelona Consensus Conference participants ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2012; 95 (02) 157-176
    CrossrefPubMedGoogle Scholar
  • 46 Boudreaux JP, Klimstra DS, Hassan MM. , et al; North American Neuroendocrine Tumor Society (NANETS) The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas 2010; 39 (06) 753-766
    CrossrefPubMedGoogle Scholar
  • 47 Kulke MH, Anthony LB, Bushnell DL. , et al; North American Neuroendocrine Tumor Society (NANETS) NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010; 39 (06) 735-752
    CrossrefPubMedGoogle Scholar
  • 48 Knigge U, Hansen CP, Stadil F. Interventional treatment of neuroendocrine liver metastases. Surgeon 2008; 6 (04) 232-239
    CrossrefPubMedGoogle Scholar
  • 49 Gupta S, Johnson MM, Murthy R. , et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 2005; 104 (08) 1590-1602
    CrossrefPubMedGoogle Scholar
  • 50 Su YK, Mackey RV, Riaz A. , et al. Long-term hepatotoxicity of yttrium-90 radioembolization as treatment of metastatic neuroendocrine tumor to the liver. J Vasc Interv Radiol 2017; 28 (11) 1520-1526
    CrossrefPubMedGoogle Scholar
  • 51 Tomozawa Y, Jahangiri Y, Pathak P. , et al. Long-term toxicity after transarterial radioembolization with yttrium-90 using resin microspheres for neuroendocrine tumor liver metastases. J Vasc Interv Radiol 2018; 29 (06) 858-865
    CrossrefPubMedGoogle Scholar
  • 52 Hamiditabar M, Ali M, Bolek L, Vahdati G, Tworowska I, Delpassand ES. Safety and effectiveness of 177Lu-DOTATATE peptide receptor radionuclide therapy after regional hepatic embolization in patients with somatostatin-expressing neuroendocrine tumors. Clin Nucl Med 2017; 42 (11) 822-828
    CrossrefPubMedGoogle Scholar
  • 53 Riff BP, Yang YX, Soulen MC. , et al. Peptide receptor radionuclide therapy-induced hepatotoxicity in patients with metastatic neuroendocrine tumors. Clin Nucl Med 2015; 40 (11) 845-850
    CrossrefPubMedGoogle Scholar
  • 54 Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P. ; NET-Liver-Metastases Consensus Conference Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford) 2015; 17 (01) 29-37
    CrossrefPubMedGoogle Scholar
  • 55 Chen JX, Rose S, White SB. , et al. Embolotherapy for neuroendocrine tumor liver metastases: prognostic factors for hepatic progression-free survival and overall survival. Cardiovasc Intervent Radiol 2017; 40 (01) 69-80
    CrossrefPubMedGoogle Scholar
  • 56 Haug AR, Rominger A, Mustafa M. , et al. Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors. J Nucl Med 2011; 52 (11) 1679-1683
    CrossrefPubMedGoogle Scholar
  • 57 Cherk MH, Kong G, Hicks RJ, Hofman MS. Changes in biodistribution on 68Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging 2018; 18 (01) 3
    CrossrefPubMedGoogle Scholar
  • 58 Ayati N, Lee ST, Zakavi R. , et al. Long-acting somatostatin analog therapy differentially alters 68Ga-DOTATATE uptake in normal tissues compared with primary tumors and metastatic lesions. J Nucl Med 2018; 59 (02) 223-227
    CrossrefPubMedGoogle Scholar
  • 59 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 (08) 1310-1316
    Google Scholar
  • 60 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 (03) 383-390
    CrossrefPubMedGoogle Scholar
  • 61 Severi S, Sansovini M, Ianniello A. , et al. 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) 1955-1963
    CrossrefPubMedGoogle Scholar
  • 62 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 (02) 302-311
    CrossrefPubMedGoogle Scholar
  • 63 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 (09) 561-569
    CrossrefPubMedGoogle Scholar
  • 64 Claringbold PG, Turner JH. Pancreatic neuroendocrine tumor control: durable objective response to combination 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy. Neuroendocrinology 2016; 103 (05) 432-439
    CrossrefPubMedGoogle Scholar
  • 65 Claringbold PG, Turner JH. Neuroendocrine tumor therapy with lutetium-177-octreotate and everolimus (NETTLE): a phase I study. Cancer Biother Radiopharm 2015; 30 (06) 261-269
    CrossrefPubMedGoogle Scholar
  • 66 Seregni E, Maccauro M, Chiesa C. , et al. 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 (02) 223-230
    CrossrefPubMedGoogle Scholar
  • 67 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) 1788-1797
    CrossrefPubMedGoogle Scholar
  • 68 Wu Y, Pfeifer AK, Myschetzky R. , et al. 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 (04) 344-355
    CrossrefPubMedGoogle Scholar
  • 69 Nonnekens J, van Kranenburg M, Beerens CE. , et al. Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib. Theranostics 2016; 6 (11) 1821-1832
    CrossrefPubMedGoogle Scholar
  • 70 McStay MK, Maudgil D, Williams M. , et al. Large-volume liver metastases from neuroendocrine tumors: hepatic intraarterial 90Y-DOTA-lanreotide as effective palliative therapy. Radiology 2005; 237 (02) 718-726
    CrossrefPubMedGoogle Scholar
  • 71 Kratochwil C, López-Benítez R, Mier W. , et al. Hepatic arterial infusion enhances DOTATOC radiopeptide therapy in patients with neuroendocrine liver metastases. Endocr Relat Cancer 2011; 18 (05) 595-602
    CrossrefPubMedGoogle Scholar
  • 72 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 (06) 551-558
    PubMedGoogle Scholar
  • 73 Kratochwil C, Giesel FL, López-Benítez R. , et al. Intraindividual comparison of selective arterial versus venous 68Ga-DOTATOC PET/CT in patients with gastroenteropancreatic neuroendocrine tumors. Clin Cancer Res 2010; 16 (10) 2899-2905
    CrossrefPubMedGoogle Scholar
  • 74 Kratochwil C, Giesel FL, Bruchertseifer F. , et al. 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) 2106-2119
    CrossrefPubMedGoogle Scholar
  • 75 van Vliet EI, van Eijck CH, de Krijger RR. , et al. Neoadjuvant treatment of nonfunctioning pancreatic neuroendocrine tumors with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med 2015; 56 (11) 1647-1653
    CrossrefPubMedGoogle Scholar
  • 76 Chan HS, Konijnenberg MW, Daniels T. , et al. Improved safety and efficacy of 213Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with L-lysine. EJNMMI Res 2016; 6 (01) 83
    CrossrefPubMedGoogle Scholar
  • 77 Sgouros G. Alpha-particles for targeted therapy. Adv Drug Deliv Rev 2008; 60 (12) 1402-1406
    CrossrefPubMedGoogle Scholar
  • 78 Dodson H, Wheatley SP, Morrison CG. Involvement of centrosome amplification in radiation-induced mitotic catastrophe. Cell Cycle 2007; 6 (03) 364-370
    CrossrefPubMedGoogle Scholar
  • 79 Chan HS, Konijnenberg MW, de Blois E. , et al. Influence of tumour size on the efficacy of targeted alpha therapy with (213)Bi-[DOTA(0),Tyr(3)]-octreotate. EJNMMI Res 2016; 6 (01) 6
    CrossrefPubMedGoogle Scholar
  • 80 Giesel FL, Wulfert S, Zechmann CM. , et al. Contrast-enhanced ultrasound monitoring of perfusion changes in hepatic neuroendocrine metastases after systemic versus selective arterial 177Lu/90Y-DOTATOC and 213Bi-DOTATOC radiopeptide therapy. Exp Oncol 2013; 35 (02) 122-126
    PubMedGoogle Scholar
  • 81 Schwartz J, Jaggi JS, O'Donoghue JA. , et al. Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody. Phys Med Biol 2011; 56 (03) 721-733
    CrossrefPubMedGoogle Scholar
  • 82 Wild D, Fani M, Fischer R. , et al. Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: a pilot study. J Nucl Med 2014; 55 (08) 1248-1252
    CrossrefPubMedGoogle Scholar
  • 83 Walker RC, Smith GT, Liu E, Moore B, Clanton J, Stabin M. Measured human dosimetry of 68Ga-DOTATATE. J Nucl Med 2013; 54 (06) 855-860
    CrossrefPubMedGoogle Scholar