title: Imaging of bronchioloalveolar carcinoma in the mice with the αⅤβ3 integrin-targeted tracer (99m)Tc-RGD-4CK.
abstract: Receptor-based imaging agents have shown improved specificity and sensitivity of cancer diagnosis by targeting the specific features of cancer. Here we reported the (99m)Tc-labeling of a cyclic polypeptide RGD-4CK and the characterization of this agent in vitro and in bronchioloalveolar carcinoma (BAC) xenograft model. The αⅤβ3 integrin receptor binding affinity of (99m)Tc-RGD-4CK was determined in BAC. The cancer targeting properties of (99m)Tc-RGD-4CK were determined in NCI-H358 xenografted nude mice. Moreover, the BAC uptake of (99m)Tc-RGD-4CK was blocked with nonradiolabeled RGD-4CK in xenografts. The competitive assay showed that (99m)Tc-RGD-4CK exhibited high specificity to BAC cell line NCI-H358. Biodistribution studies indicated that (99m)Tc-RGD-4CK exhibited high tumor uptake (4.12 ± 1.21% injected dose/g 120 minutes after injection) and prolonged tumor retention (2.08 ± 0.33% injected dose/g 240 minutes after injection) in NCI-H358 xenografted nude mice. Moreover, (99m)Tc-RGD-4CK produced a good tumor-to-lung ratio (2.38) because of low lung activity accumulation 120 minutes postinjection. BAC on the flank of xenografted mice was clearly visualized by single photon emission computed tomography/computed tomography imaging using (99m)Tc-RGD-4CK. In conclusion, this study provides evidence that (99m)Tc-RGD-4CK is a promising agent for noninvasive determination of αⅤβ3 integrin status and therapy monitoring in BAC.
authors.affiliation: Department of Nuclear Medicine, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Zhang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Jia
authors.forename: Zhong-Ying
authors.initials: ZY
authors.lastname: Li
authors.forename: Jue
authors.initials: J
authors.lastname: Feng
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D015609:Organotechnetium Compounds; C047981:arginyl-glycyl-aspartic acid
keywords: (18)F-FDG; (18)F-fluorodeoxyglucose; BAC; CT; MIBI; N-ethoxy, N-ethyl dithiocarbamate; NOET; NSCLC; PET; RGD; SPECT; arginine-glycine-aspartate; bronchioloalveolar carcinoma; computed tomography; methoxyisobutyl isonitrile; non–small-cell lung cancer; positron emission tomography; single photon emission computed tomography