title: Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.
abstract: This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation.
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Shanqun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Molecular Targeting Technologies, Inc, West Chester, PA 19380, USA.
authors.forename: Koon Y
authors.initials: KY
authors.lastname: Pak
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China. Electronic address: cheng.dengfeng@zs-hospital.sh.cn.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005937:Glucaric Acid / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D013667:Technetium; D005937:Glucaric Acid
keywords: (99m)Tc-glucarate ((99m)Tc-GLA); Fructose; Glucose transporter 5 (GLUT5); Imaging agent; Non-small cell lung cancer (NSCLC); SPECT/CT