title: Development of (177)Lu-DOTA-Dendrimer and Determination of Its Effect on Metal and Ion Levels in Tumor Tissue.
abstract: Dendrimers are synthetic nanomolecules with well-defined chemical structures. Different strategies have been used for radiolabeling dendrimers with different radioisotopes. In this study, the aim was to conjugate dendrimers with (177)Lu, to observe the in vivo behavior of the labeled compound and to measure the elementary changes in tumor tissue that could be caused by ionizing radiation. PAMAM G4 dendrimers conjugated with DOTA were labeled with (177)Lu. The radiolabeled compound was characterized and its stability was evaluated by reverse phase high performance liquid chromatography. Radiolabeling yield was >98% and stable for 24 hours. Biodistribution studies of (177)Lu-DOTA-dendrimers in C57BL/6 melanoma-bearing mice showed blood clearance with hepatic and renal depuration and tumor uptake. The concentrations of Br, Ca, Cl, Fe, K, Mg, Na, Rb, S, and Zn were determined in tumor tissues of C57BL/6 mice treated with (177)Lu-DOTA-dendrimers and in untreated mice. The results showed decreased concentrations of Br (62%), Ca (24%), Cl (51%), K (12%) and Na (60%) and increased concentrations of Fe (8%), Mg (28%), Rb (100%), S (6%) and Zn (4%) in tumor tissues of mice treated with (177)Lu-DOTA-dendrimers. These data may be useful to evaluate changes in tumor tissues as indicators of damage that could be caused by ionizing radiation.
authors.affiliation: 1 Centro do Reator de Pesquisas (CRPq), Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN - SP) , São Paulo, Brasil .
authors.forename: Luciana
authors.initials: L
authors.lastname: Kovacs
authors.affiliation: 2 Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Universidad de la República , Montevideo, Uruguay .
authors.forename: Marcos
authors.initials: M
authors.lastname: Tassano
authors.affiliation: 2 Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Universidad de la República , Montevideo, Uruguay .
authors.forename: Mirel
authors.initials: M
authors.lastname: Cabrera
authors.affiliation: 1 Centro do Reator de Pesquisas (CRPq), Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN - SP) , São Paulo, Brasil .
authors.forename: Cibele B
authors.initials: CB
authors.lastname: Zamboni
authors.affiliation: 2 Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Universidad de la República , Montevideo, Uruguay .
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández
authors.affiliation: 3 Instituto de Física, Universidade Federal Fluminense , Niterói, Brasil .
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Anjos
authors.affiliation: 2 Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Universidad de la República , Montevideo, Uruguay .
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D007477:Ions / Q000378:metabolism; D008187:Lutetium / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology*; D011868:Radioisotopes / Q000737:chemistry / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism*; D013388:Succinimides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C502492:DOTA-NHS; D050091:Dendrimers; D007477:Ions; D008670:Metals; D009757:Nylons; C520550:PAMAM-G4; D011868:Radioisotopes; D013388:Succinimides; D008187:Lutetium
keywords: 177Lu; PAMAM G4 dendrimers; neutron activation analyses; trace elements; tumor