Production and Investigation of Radiopharmaceutical Nanoconstruction [ 212 Pb]DOTATATE for Therapy of Malignant Neoplasm
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roduction and Investigation of Radiopharmaceutical Nanoconstruction [212Pb]DOTATATE for Therapy of Malignant Neoplasms K. Kokova, b, *, A. Demchenkoc, B. Egorovad, A. Larkina, A. Lyundupc, K. Makoveevaa, A. Moiseevaa, V. Panchenkoa, b, M. Proshina, I. Reshetova, c, and D. Chuvilina, b aNational
Research Center “Kurchatov Institute,” Moscow, 123182 Russia Faculty of Physics, Moscow State University, Moscow, 11991 Russia c Sechenov First Moscow State Medical University, Moscow, 119146 Russia dFaculty of Chemistry, Moscow State University, Moscow, 119991 Russia *e-mail: [email protected] b
Received July 7, 2019; revised August 15, 2019; accepted August 19, 2019
Abstract—A method for obtaining radiopharmaceutical nanoconstruction [212Pb]DOTATATE for investigations in the field of neuroendocrine tumors therapy has been developed. A laboratory generator of β-emitting radionuclide 212Pb with an operating efficiency of 40% has also been developed. To determine the cytotoxic effect of the [212Pb]DOTATATE complex, somatostatin receptor-expressing pancreatic cancer cells (Rinm5F cell line) were incubated with [212Pb]DOTATATE for 22 h; cell survival was determined using Presto Blue analysis. Keywords: radiopharmaceuticals, biological nanoconstructions, nuclear medicine, radionuclides production, cytotoxicity DOI: 10.1134/S102745102007023X
INTRODUCTION Targeted effect on tumoral tissues is the crucial issue of modern fundamental and practical oncology. The essence of the targeted therapy method consists in delivery of toxic preparations to cancer cells by means of artificially made biochemical nanostructures (bioconjugates) that have an ability of selective attachment to surface receptors on a cancer cell with healthy tissues remaining unaffected. One of the targeted therapy methods is the socalled peptide receptor radionuclide therapy, the main point of which is the cancer cell damaging with shortlived α-emitting radionuclides (α-emitters) complexing with synthetic peptides specific to receptors of a number of tumors referred to as neuroendocrine tumors [1, 2]. The following radionuclides can be used as α-emitters in targeted therapy: 149Tb (T1/2 4.12 h), 212Bi (T 213Bi (T 225Ac (T 1/2 60 min), 1/2 46 min), 1/2 10 days) and some others [3–6]. α-particles are characterized by high energy (5–8 MeV) and a short track in a substance (10–100 μm); therefore, the localization of a sufficient amount of α-emitter ions in close proximity to a tumor cell results in selective destruction of malignant neoplasms with the minimal damage of surrounding tissues. Complexes including synthetic pep-
tides or monoclonal antibodies [7, 8] specific for a definite tumor antigen and chelating agents that are capable of binding valence ions of radionuclides can be used as nanostructures for selective drug delivery to tumor tissues. The development of targeted preparations for radionuclide therapy, labeled with different α-emitters, has been in progress since the late 1980s and is currently undergoing even greater dynamics [9, 10]. Application of sho
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