Biodistribution Studies of 177Lu-DOTATOC in Mouse Tumor Model: Possible Utilization in Adenocarcinoma Breast Cancer Treatment
Despite the appropriate characteristics of 177Lu and DOTATOC, to our best knowledge, the therapeutic benefit of 177Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of 177Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.177Lu was prepared with the specific activity of 2.6-3 GBq.mg-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with 177Lu-DOTATOC as an ideal therapeutic agent.
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 L. Bodei, J. Mueller-Brand, R. P. Baum, M. E. Pavel, D. Hörsch, M. S. O'Dorisio, T. M. O'Dorisio, J. R. Howe, M. Cremonesi, D. J. Kwekkeboom and J. J. Zaknun, “The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours.” Eur J Nucl Med Mol Imaging, vol. 40, pp. 800-816, 2013.
 B. Stolz, G. Weckbecker, P.M. Smith-Jones, R. Albert, F. Raulf and C. Bruns, “The somatostatin receptor-targeted radiotherapeutic (90Y-DOTA-DPhe1, Tyr3) octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours.” Eur J Nucl Med, vol.25, pp. 668-674, 1998.
 J. C. Reubi, J. Laissue, E. Krenning and S. W. Lamberts, “Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications.” J Steroid Biochem Mol Biol, vol. 43, pp. 27-35, 1992.
 A. E. Lanfranchi and P. Fagan, “Breast cancer and induced abortion: a comprehensive review of breast development and pathophysiology” the epidemiologic literature, and proposal for creation of databanks to elucidate all breast cancer risk factors. Issues Law Med, vol. 29, pp. 3-133, 2014.
 F. Al-Ejeh, J. M. Darby, B. Thierry and M. P. Brown, “A simplified suite of methods to evaluate chelator conjugation of antibodies: effects on hydrodynamic radius and biodistribution.” Nucl Med Biol, vol. 36, pp. 395-402, 2009.
 A. G. Harris, “Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects.” Gut, vol. 35, pp. 1-4, 1994.
 P. P. Kamat, S. Gupta, J. E. Ensor, R. Murthy, K. Ahrar, D. C. Madoff, M. J. Wallace and M. E. Hicks, “Hepatic arterial embolization and chemoembolization in the management of patients with large-volume liver metastases.” Cardiovasc Intervent Radiol, vol. 31, pp. 299-307, 2008.
 A. K. Pfeifer, T. Gregersen, H. Grønbæk, C. P. Hansen, J. Müller-Brand, K. Herskind Bruun, K. Krogh, A. Kjær and U. Knigge, “Peptide Receptor Radionuclide Therapy with 90Y-DOTATOC and 177Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland.” Neuroendocrinology, vol. 93, pp. 189-196, 2011.
 A. Frilling, F. Weber, F. Saner, A. Bockisch, M. Hofmann, J. Mueller-Brand and C. E. Broelsch, “Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors.” Surgery, vol. 140, pp. 968-976, 2006.
 T. D. Poeppel, I. Binse, S. Petersenn, H. Lahner, M. Schott, G. Antoch, W. Brandau, A. Bockisch and C. Boy, “Differential uptake of (68)Ga-DOTATOC and (68)Ga-DOTATATE in PET/CT of gastroenteropancreatic euroendocrine tumors.” Recent Results Cancer Res, vol. 194, pp. 353-371, 2013.
 H. Yousefnia, A. R. Jalilian, F. Abbasi-Davani, S. Zolghadri, A. Bahrami-Samani, M. Ghannadi-Maragheh and M. Mazidi, “Preparation and quality control of 177Lu-chitosan for radiosynovectomy” Iran J Nucl Med, vol. 22, pp. 1-6, 2014.
 J. Yuan, C. Liu, X. Liu, Y. Wang, D. Kuai, G. Zhang and J. J. Zaknun, “Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study.” Clin Nucl Med, vol. 38, pp. 88-92, 2013.
 M. Danthala, K. G. Kallur, G. R. Prashant, K. Rajkumar and M. Raghavendra Rao, “(177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India.” Eur J Nucl Med Mol Imaging, vol. 41, pp. 1319-1326, 2014.
 H. Yousefnia, M. Mousavi-Daramoroudi, S. Zolghadri and F. Abbasi-Davani, “Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies” IJNM, vol. 24, pp. 85-91, 2016.
 H. Yousefnia, E. Radfar, A. R. Jalilian, A. Bahrami-Samani, S. Shirvani-Arani, A. Arbabi and M. Ghannadi-Maragheh, “Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy” J Radioanal Nucl Chem, vol. 287, pp. 199-209, 2011.
 E. Raymond, S. Faivre and P.H. Ruszniewski, “Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract.” USA: Springer, 2014.