title: A HER2-targeted RNA aptamer molecule labeled with 99mTc for single-photon imaging in malignant tumors.
abstract: A modified RNA aptamer with HER2-specific binding was conjugated to hynic and labeled with (99m)Tc, for potential use as a radiopharmaceutical for diagnostic imaging of ovarian cancer cells (SKOV-3) with high HER2 expression. The aptamer was radiolabeled with (99m)Tc by using hynic as the chelator and tricine as the co-ligand. Stability testing of the radioconjugated aptamer was performed via ITLC and SDS-PAGE in normal saline and serum. The aptamer-radionuclide conjugate was evaluated for cellular HER2-specific binding, saturation affinity, and cellular internalization in SKOV-3 and MCF-7 cells, and its biodistribution properties were assessed in normal and SKOV-3 tumor-bearing mice. Radiolabeling of the aptamer was achieved with high yield and radiochemical purity, and the (99m)Tc-hynic-RNA aptamer was highly stable in normal saline and serum. Cellular experiments showed specific binding of the aptamer to the HER2 receptor with a dissociation constant of 27 nM. Rapid blood clearance was observed after injection of the (99m)Tc-hynic-RNA aptamer, and the main excretion route was via the hepatobilary system. While the radioconjugated aptamer bound specifically to the HER2 receptor on cells in vitro, it did not show any significant tumor-to-blood or tumor-to-muscle ratios in mice. Modifications to radiolabeled aptamer will require improving its pharmacokinetic properties and tumor uptake in vivo.
authors: Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Kambiz
authors: K
authors: Varmira
authors: Seyed Jalal
authors: SJ
authors: Hosseinimehr
authors: Zohreh
authors: Z
authors: Noaparast
authors: Seyed Mohammad
authors: SM
authors: Abedi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D017785:Photons; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013667:Technetium
chemical_list: D052157:Aptamers, Nucleotide; D018719:Erb-b2 Receptor Tyrosine Kinases; D013667:Technetium; C508053:ERBB2 protein, human
keywords: (99m)Tc; Aptamer; HER2; Radionuclide; Specific binding