title: Tumor targeting with a (99m)Tc-labeled AS1411 aptamer in prostate tumor cells.
abstract: AS1411, a 26-base guanine-rich oligonucleotide aptamer, has high affinity to nucleolin, mainly on tumor cell surfaces. In this study, a modified AS1411 was labeled with (99m)Tc and evaluated as a potential tumor-targeting agent for imaging. The AS1411 aptamer was conjugated with HYNIC and labeled with (99m)Tc in the presence a co-ligand. Radiochemical purity and stability testing of the (99m)Tc-HYNIC-AS1411 aptamer were carried out with thin layer chromatography and a size-exclusion column in normal saline and human serum. Cellular nucleolin-specific binding, cellular internalization in DU-145 cells, as high levels of nucleolin expression, were performed. Additionally, biodistribution in normal mice and DU-145 tumour-bearing mice was assessed. Radiolabeling of the aptamer resulted in a reasonable yield and radiochemical purity after purification. The aptamer was stable in normal saline and human serum, and cellular experiments demonstrated specific binding of the AS1411 aptamer to the nucleolin protein. Based on biodistribution assessment of (99m)Tc-HYNIC-AS1411, rapid blood clearance was seen after injection and it appears that the excretion route was via the urinary system at 1 h post-injection. Tumours also showed a higher accumulation of radioactivity with this labeled aptamer. (99m)Tc-AS1411 can be a potential tool for the molecular imaging of nucleolin-overexpressing cancers.
authors: Department of Radiopharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences , Sari , Iran and.
authors: Zohreh
authors: Z
authors: Noaparast
authors: Seyed Jalal
authors: SJ
authors: Hosseinimehr
authors: Majid
authors: M
authors: Piramoon
authors: Seyed Mohammad
authors: SM
authors: Abedi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010750:Phosphoproteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D016601:RNA-Binding Proteins / Q000378:metabolism; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D006834:Hydrazines; D009539:Nicotinic Acids; D009838:Oligodeoxyribonucleotides; D015609:Organotechnetium Compounds; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C120392:6-hydrazinopyridine-3-carboxylic acid; C513936:AGRO 100
keywords: 99mTc; AS1411; aptamer; nucleolin; targeting; tumor