Evaluation of the Possible Utilization of 68Ga-DOTATOC in Diagnosis of Adenocarcinoma Breast Cancer

Document Type : Original Article


1 Nuclear Science and Technology Research Institute (NSTRI)

2 University of Zanjan , Zanjan, Iran, Postal Code: 4537138791

3 nuclear science and technology research institute

4 tehran university


Objective(s): Studies have indicated advantageous properties of [DOTA-DPhe1 , Tyr3 ] octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is the second leading cause of cancer mortality in women, and most of these cancers are often an adenocarcinoma. Due to the importance of target to non-target ratios in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an adenocarcinoma breast cancer animal model was studied in this research, and the optimized time for imaging was determined. Methods: 68Ga was obtained from 68Ge/68Ga generator. The complex was prepared at optimized conditions. Radiochemical purity of the complex was checked using both HPLC and ITLC methods. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer. Also, PET/CT imaging was performed up to 120 min post injection. Results: The complex was produced with radiochemical purity of greater than %98 and specific activity of about 40 GBq/mM at optimized conditions. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer indicated fast blood clearance and significant uptake in the tumor. Significant tumor:blood and tumor:muscle uptake ratios were observed even at early times postinjection. PET/CT images were also confirmed the considerable accumulation of the tracer in the tumor. Conclusion: Generally, the results proved the possible application of the radiolabelled complex for the detection of the adenocarcinoma breast cancer and according to the pharmacokenitic data, the suitable time for imaging was determined as at least 30 min after injection.


Main Subjects


    1. Aghanejad A, Jalilian AR, Ardaneh K, Bolourinovin F, Yousefnia H, Samani AB. Preparation and quality control of 68Ga-Citrate for PET applications. Asia Oceania J Nucl Med Biol. 2015;3(2):99-106.
    2. Zolghadri S, Yousefnia H, Jalilian AR, Ghannadi- Maragheh M. Production, biodistribution assessment and dosimetric evaluation of 177Lu-TTHMP as an agent for bone pain palliation. Asia Oceania J Nucl Med Biol. 2015;3(1):35-42.3.
    3. Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006;36(3):228-47.
    4. Reubi JC, Laissue J, Krenning E, Lamberts SW. Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol. 1992;43(1- 3):27-35.
    5. Kwekkeboom DJ, van Urk H, Pauw BK, Lamberts SW, Kooij PP, Hoogma RP, et al. Octreotide scintigraphy for the detection of paragangliomas. J Nucl Med. 1993;34(6):873-8.
    6. Stolz B, Weckbecker G, Smith-Jones PM, Albert R, Raulf F, Bruns C. The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-DPhe1,Tyr3] octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumors. Eur J Nucl Med. 1998;25(7):668-74.
    7. 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.
    8. Pfeifer AK, Gregersen T, Grønbæk H, Hansen CP, Müller- Brand J, Herskind Bruun K, 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(3):189-96.
    9. Breeman WA, de Jong M, de Blois E, Bernard BF, Konijnenberg M, Krenning EP. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging. 2005;32(4):478-85.
    10. Froidevaux S, Eberle AN, Christe M, Sumanovski L, Heppeler A, Schmitt JS, et al. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model. Int J Cancer. 2002;98(6):930-7.
    11. Naderi M, Zolghadri S, Yousefnia H, Ramazani A, Jalilian AR. Preclinical study of 68Ga-DOTATOC: biodistribution assessment in syrian rats and evaluation of absorbed dose in human organs. Asia Ocean J Nucl Med Biol. 2016;4(1):19-29.
    12. Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schäfer M, et al. Comparison of 68Ga- DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2007;34(10):1617-26.
    13. Van Binnebeek S, Vanbilloen B, Baete K, Terwinghe C, Koole M, Mottaghy FM, et al. Comparison of diagnostic accuracy of 111In-pentetreotide SPECT and 68Ga-DOTATOC PET/CT: a lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours. Eur Radiol. 2016;26(3):900-9.
    14. Sollini M, Erba PA, Fraternali A, Casali M, Di Paolo ML, Froio A, et al. PET and PET/CT with 68Gallium- Labeled Somatostatin Analogues in Non GEP-NETs Tumors. Sci World J. 2014; 2014:194123.
    15. Samson DJ, Flamm CR, Pisano ED, Aronson N. Should FDG PET be used to decide whether a patient with an abnormal mammogram or breast finding at physical examination should undergo biopsy? Acad Radiol. 2002;9(7):773-83.
    16. Chereau E, Durand L, Frati A, Prignon A, Talbot JN, Rouzier R. Correlation of immunohistopathological expression of somatostatin receptor-2 in breast cancer and tumor detection with 68Ga-DOTATOC and 18F-FDG PET imaging in an animal model. Anticancer Res. 2013;33(8):3015-9.
    17. Sharifi M, Yousefnia H, Zolghadri S, Bahrami-Samani A, Naderi M, Jalilian AR, et al. Preparation and biodistribution assessment of 68Ga-DKFZ-PSMA-617 for PET prostate cancer imaging. Nucl Sci Tech. 2016;27(6):142-151.
    18. Alizadeh AM, Azizian S, Fayazi HR, Mousavi MS, Nabavi SA. Mouse spontaneous mammary adenocarcinoma as a suitable model of breast cancer in Iran. Basic Clin Cancer Res. 2011;3(3-4):30-3.
    19. Sharifi M, Yousefnia H, Bahrami-Samani A, Jalilian AR, Zolghadri S, Alirezapour B, et al. Optimized production, quality control, biological evaluation and PET/CT imaging of 68Ga-PSMA-617 in breast adenocarcinoma model. Radiochim Acta. 2017;105(5):399-407.
    20. Firestone RB, Shirley VS. Table of isotopes. Weinheim, Germany: Wiley-VCH; 1998. P. 3168.
    21. Breeman WA, de Jong M, de Blois E, Bernard BF, Konijnenberg M, Krenning EP. Radiolabeling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging. 2005;32(4):478-85.
    22. Gallium (68Ga) edotreotide injection. European Pharmacopoeia. Available at: URL: http://www.esrr. info/wp-content/uploads/2016/04/Kroon.pdf; 2014. P. 1062.
    23. de Blois E, Sze Chan H, Naidoo C, Prince D, Krenning EP, Breeman WA. Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides. Appl Radiat Isot. 2011;69(2):308-15.
    24. Velikyan I. 68Ga-based radiopharmaceuticals: production and application relationship. Molecules. 2015;20(7):12913-43.
    25. Aghanejad A, Jalilian AR, Maus S, Yousefnia H, Geramifar P, Beiki D. Optimized production and quality control of 68Ga-DOTATATE. Iran J Nucl Med. 2016;24(1):29-36.
    26. Raymond E, Faivre S, Ruszniewski P. Management of neuroendocrine tumors of the pancreas and digestive tract. New York, USA: Springer; 2014.
    27. Pederzoli P, Bassi C. Uncommon pancreatic neoplasms. Berlin, Germany: Springer Science & Business Media; 2012.
    28. Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol. 2014;55(4):389-98.