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|Title:||177Lu-Dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity: A potential theranostic radiopharmaceutical||Keywords:||Dendrimers;Gold nanoparticles;Theranostic Radiopharmaceutical;info:eu-repo/classification/cti/2||Description:||177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4)-folate-bombesin with gold nanoparticles (AuNPs) in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs) and gastrin-releasing peptide receptors (GRPRs) overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer.The carboxylate groups of Lys1Lys3(DOTA)-bombesin and folic acid were activatedwithHATUand also conjugated to the dendrimer.The conjugate was mixed with 1%HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS), particle size distribution (DLS), TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%). Fluorescence results demonstrated that the presence ofAuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15 ± 2.72%). 177Ludendrimer( AuNP)-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.
CONACYT-SEP-CB-2014-01-242443 International Atomic Energy Agency (Grant 18358) LaboratorioNacional de Investigaci´on yDesarrollo de Radiof´armacos, CONACyT
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