Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

Document Type: Technical note

Authors

1 Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia

2 Faculty of Health Sciences, University of Sydney, Sydney, Australia

3 Sydney Medical School, University of Sydney, Sydney, Australia

4 Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia

Abstract

Objective(s): Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.
Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMPcertified
peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.
Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period.
Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

Keywords


1. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003; 97(4):934-59.

2. Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003; 24(4):389-427.

3. Reubi JC, Waser B. Concomitant expression of several peptide receptors in Neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003; 30(5):781-93.

4. Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq [90Y]-DOTATOC. J Nucl Med. 2002; 43(5):610-6.

5. Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177]Lu-DOTA(0),Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003; 30(3):417-22.

6. Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, et al. Radiolabeled somatostatin analog [177Lu]-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol. 2005; 23(12):2754-62.

7. Hofman MS, Hicks RJ. Peptide receptor radionuclide therapy for neuroendocrine tumours: standardized and randomized, or personalized? Eur J Nucl Med Mol Imaging. 2014; 41(2):211-3.

8. Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, et al. Cohort study of somatostatinbased radiopeptide therapy with [90Y-DOTA]-TOC

versus [90Y -DOTA]-TOC plus [177Lu -DOTA]-TOC in neuroendocrine cancers. J Clin Oncol. 2012; 30(10):1100-6.

9. Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu -DOTAOTyr3] octreotate: comparison with [111In-DTPA]octreotide in patients. Eur J Nucl Med. 2001; 28(9):1319-25.

10. Decristoforo C, Knopp R, von Guggenberg E, Rupprich M, Dreger T, Hess A, et al. A fully automated synthesis for the preparation of 68Ga-labelled peptides. Nucl Med Commun. 2007; 28(11):870-5.

11. Ocak M, Antretter M, Knopp R, Kunkel F, Petrik M, Bergisadi N, et al. Full automation of (68)Ga labeling of DOTA-peptides including cation exchange prepurification. Appl Radiat Isot. 2010; 68(2):297-302.

12. Petrik M, Knetsch PA, Knopp R, Imperato G, Ocak M, von Guggenberg E, et al. Radiolabelling of peptides for PET, SPECT and therapeutic applications using a fully automated disposable cassette system. Nucl Med Commun. 2011; 32(10):887-95.

13. De Decker M, Turner JH. Automated module radiolabeling of peptides and antibodies with gallium-68, lutetium-177 and iodine-131. Cancer Biother Radiopharm. 2012; 27(1):72-6.

14. 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.

15. Aslani A, Snowdon GM, Bailey DL, Schembri GP, Bailey EA, Roach PJ. Gallium-68 DOTATATE production with automated PET radiopharmaceutical synthesis system: A three year experience. Asia Oceania J Nucl Med Biol. 2014; 2(2):75-86.

16. Bakker WH, Breeman WA, Kwekkeboom DJ, DeJong LC, Krenning EP. Practical aspects of peptide receptor radionuclide therapy with [177Lu][DOTA0, Tyr3] octreotate. Q J Nucl Med Mol Imaging. 2006; 50(4):265-71.

17. Breeman WA, de Jong M, Visser TJ, Erion JL, Krenning EP. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging. 2003; 30(6):917-20.