title: Multimeric system of 99mTc-labeled gold nanoparticles conjugated to c[RGDfK(C)] for molecular imaging of tumor α(v)β(3) expression.
abstract: Integrin α(V)β(3) plays a critical role in tumor angiogenesis and metastasis. Suitably radiolabeled cyclic RGD peptides can be used for noninvasive imaging of α(V)β(3) expression. The aim of this research was to prepare a multimeric system of technetium-99m-labeled gold nanoparticles conjugated to c[RGDfK(C)] and to evaluate its biological behavior as a potential radiopharmaceutical for molecular imaging of tumor angiogenesis. Hydrazinonicotinamide-GGC (HYNIC-GGC) and c[RGDfK(C)] peptides were synthesized and conjugated to gold nanoparticles (AuNP, 20 nm) by means of spontaneous reaction of the thiol groups of cysteine. The nanoconjugate was characterized by TEM, FT-IR, UV-vis, XPS, and Raman spectroscopy. To obtain (99m)Tc-HYNIC-GGC-AuNP-c[RGDfK(C)] ((99m)Tc-AuNP-RGD), the (99m)Tc-HYNIC-GGC radiopeptide was first prepared and added to 1.5 mL of AuNP solution (1 nM) followed by c[RGDfK(C)] (10 μL, 50 μM) at 18 °C with stirring for 15 min. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in α(V)β(3) receptor-positive C6 glioma cancer cells. Biodistribution studies were accomplished in athymic mice with C6-induced tumors with blocked and nonblocked receptors, and images were obtained using a micro-SPECT/CT. TEM and spectroscopy techniques demonstrated that AuNPs were functionalized with peptides. RP was 96 ± 2% without postlabeling purification. (99m)Tc-AuNP-RGD showed specific recognition for α(V)β(3) integrins expressed in C6 cells, and 3 h after i.p. administration in mice, the tumor uptake was 8.18 ± 0.57% ID/g. Micro-SPECT/CT images showed evident tumor uptake. (99m)Tc-AuNP-RGD demonstrates properties suitable for use as a target-specific agent for molecular imaging of tumor α(V)β(3) expression.
authors.affiliation: Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Estado de México, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Morales-Avila
authors.forename: Guillermina
authors.initials: G
authors.lastname: Ferro-Flores
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Ocampo-García
authors.forename: Luis M
authors.initials: LM
authors.lastname: De León-Rodríguez
authors.forename: Clara L
authors.initials: CL
authors.lastname: Santos-Cuevas
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Becerra
authors.forename: Luis A
authors.initials: LA
authors.lastname: Medina
authors.forename: Leobardo
authors.initials: L
authors.lastname: Gómez-Oliván
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis* / Q000096:biosynthesis; D007553:Isotope Labeling; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D039302:Integrin alphaVbeta3; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D006046:Gold