title: A pilot study imaging integrin αvβ3 with RGD PET/CT in suspected lung cancer patients.
abstract: OBJECTIVE
  Angiogenesis is an essential step in tumour development and metastasis. Integrin αvβ3 plays a major role in angiogenesis, tumour growth and progression. A new tracer, (18)F-AL-NOTA-PRGD2, denoted as (18)F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin αvβ3. This is a pilot study to test the safety and diagnostic value of (18)F- arginine-glycine-aspartic acid (RGD) PET/computed tomography (CT) in suspected lung cancer patients.
  
  
  METHODS
  Twenty-six patients with suspected lung cancer on enhanced CT underwent (18)F-alfatide RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUVs) and the tumour-to-blood ratios were measured, and diagnoses were pathologically confirmed.
  
  
  RESULTS
  RGD PET/CT with (18)F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed. The (18)F-alfatide RGD PET/CT analysis correctly recognized 17 patients with lung cancer, 4 patients (hamartoma) as true negative, and 5 patients (4 chronic inflammation and 1 inflammatory pseudotumour) as false positive. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of (18)F-alfatide RGD PET/CT for the diagnosis of suspected lung cancer patients was 100, 44.44, 80.77, 77.27, and 100%, respectively. The area under a receiver operating characteristic (ROC) curve was 0.75 (P = 0.038), and ROC analysis suggested an SUVmax cut-off value of 2.65 to differentiate between malignant lesions and benign lesions. The SUV for malignant lesions was 5.37 ± 2.17, significantly higher than that for hamartomas (1.60 ± 0.11; P < 0.001). The difference between the tumour-to-blood ratio for malignant lesions (4.13 ± 0.91) and tissue of interest-to-blood ratio for hamartomas (1.56 ± 0.24) was also statistically significant (P < 0.001). Neither the SUVmax nor the tumour-to-blood ratio was significantly different between malignant lesions and inflammatory lesions or inflammatory pseudotumours (P > 0.05). Sixteen of 26 patients later underwent successful surgery, and pathologic examination confirmed nodes positive for metastasis in 14 of 152 lymph nodes. The sensitivity, specificity, accuracy, PPV, and NPV of PET/CT for lymph nodes was 92.86, 95.65, 95.40, 61.90, and 99.25%, respectively.
  
  
  CONCLUSIONS
  Our results suggest that RGD PET/CT with the new tracer (18)F-alfatide is safe and potentially effective in the diagnosis of non-small cell lung cancer. It may be used in the diagnosis of lung cancer, successfully distinguishing malignant lesions from hamartoma. However, it is difficult to clearly differentiate inflammatory or inflammatory pseudotumours from malignant lesions. Additional studies with a larger number of patients are needed to validate our findings.
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital & Institute, No 440 Jiyan Road, Jinan, Shandong, 250117, China.|School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Wuyi County People's Hospital of Hengshui City, Hengshui, Hebei Province, China.
authors.forename: Honghu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Radiology, Shandong Cancer Hospital & Institute, Jinan, Shandong, China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiology, Shandong Cancer Hospital & Institute, Jinan, Shandong, China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Shandong Cancer Hospital & Institute, Jinan, Shandong, China.
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Radiology, Shandong Cancer Hospital & Institute, Jinan, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital & Institute, No 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital & Institute, No 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital & Institute, No 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital & Institute, No 440 Jiyan Road, Jinan, Shandong, 250117, China. yuanshuanghu@sina.com.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Yuan
mesh_terms: D000368:Aged; D056831:Coordination Complexes / Q000009:adverse effects / Q000493:pharmacokinetics*; D003937:Diagnosis, Differential; D005260:Female; D006222:Hamartoma / Q000000981:diagnostic imaging*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010456:Peptides, Cyclic / Q000009:adverse effects* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed
chemical_list: D056831:Coordination Complexes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C586680:alfatide II
keywords: 18F-alfatide; Integrin αvβ3; Lung cancer; RGD PET