title: Integrin Imaging with99mTc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non-Small Cell Lung Cancer.
abstract: Purpose To evaluate an integrin imaging approach based on single photon emission computed tomography (SPECT)/computed tomography (CT) by using technetium 99m (99mTc)-dimeric cyclic arginine-glycine-aspartic acid (RGD) peptides with three polyethylene glycol spacers (3PRGD2) as the tracer to target the integrin αvβ3expression in lung cancer and lymph node metastasis. Materials and Methods With ethics committee approval and written informed consent, 65 patients (41 male, 24 female; mean age, 60 years ± 11 [standard deviation]) with suspicious lung lesions were recruited with informed consent. The patients underwent both99mTc-3PRGD2 SPECT/CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT within 1 week. Finally, 65 lung lesions in 53 patients were pathologically diagnosed as non-small cell lung cancer (NSCLC) and 14 lung lesions in 12 patients were benign. Per-region analysis of lymph nodes included 248 regions with metastasis and 56 negative regions. Twenty specimens from the removed lung lesions or lymph nodes were stained with integrin αvβ3, CD34, and Ki-67 to correlate with the image findings. Receiver operating characteristic curve, z statistics, McNemar test, and χ2analysis were used to compare the diagnostic performance of the two imaging methods. Results99mTc-3PRGD2 SPECT/CT was found to be more specific than18F-FDG PET/CT in the per-region diagnosis of lymph node metastasis (specificity, 94.6% vs 75.0%; P = .008) when the sensitivity of the two methods was comparable (88.3% vs 90.7%; P = .557). There was no significant difference between the two methods in the per-lesion diagnosis of lung tumor (z = 0.82, P = .410). The accumulation level of99mTc-3PRGD2 was found in positive correlation with the integrin αvβ3expression (r = 0.84, P = .001) and microvessel density (r = 0.63, P = .011) in the tumors. Conclusion99mTc-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from NSCLC, which may benefit surgical decision making for the patients.©RSNA, 2016.
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Xiaona
authors.initials: X
authors.lastname: Jin
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Naixin
authors.initials: N
authors.lastname: Liang
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Mengzhao
authors.initials: M
authors.lastname: Wang
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Ximin
authors.initials: X
authors.lastname: Shi
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Shanqing
authors.initials: S
authors.lastname: Li
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Jinmei
authors.initials: J
authors.lastname: Luo
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Yaping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Quancai
authors.initials: Q
authors.lastname: Cui
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Kun
authors.initials: K
authors.lastname: Zheng
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: From the Departments of Nuclear Medicine (X.J., X.S., Y.L., K.Z., F.L., Z.Z.), Thoracic Surgery (N.L., S.L.), Respiratory Medicine (M.W., J.L.), and Pathology (Y.M., Q.C.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China; Medical Isotopes Research Center, Peking University, Beijing, China (B.J., Z.L., J.S., F.W.); and Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China (F.W.).
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008479:Mediastinal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods
chemical_list: D039302:Integrin alphaVbeta3; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C561921:technetium 99m (HYNIC-3PRGD(2))(tricine)(TPPTS)