The aim of study was to evaluate the clinical value of ^99mTc-3PRGD2 SPECT/CT for the diagnosis of lung cancer and correlate with αvβ3 expression on tumor including neovasculature and tumor cell, further difference between None Small Cell Lung Cancer(NSCLC) and small cell lung cancer (SCLC) was investigated. Methods: 226 consecutive patients with high suspected lung cancer were included in this study.^99mTc-3PRGD2 SPECT/CT was performed at 1h post-injection. ROI analysis was used, tumor radiouptake was measured as the ratio of T/N. Final diagnosis was confirmed by histopathology. The expression of αvβ3, CD31 in tumor specimens were analyzed for reflecting tumor angiogenesis. Results: Out of 226 patients, 28 PTS with benign tumor, 195 PTS with malignant tumor were finally confirmed histopathology, 19 with SCLC, 155 with non-small cell lung cancer (NSCLC), 2 with mesothelioma of pleura, 7 patients with lung metastasis, 1 with neuroendocrine tumor, 1 with lymphoma. Out of 184 patients with lung cancer, 82 patients in stage Ⅳ，26 in stage Ⅲ,37 in stageⅡ,40 in stageⅠ.The sensitivity, specificity, positive predictive value, negative predictive value of ^99mTc-3PRGD2 was 92.0%, 48.0%, 93.8%, 66.7%, respectively. αvβ3 expression was significantly higher in NSCLC than SCLC, however, αvβ3 expression didn’t correlated significantly with ^99mTc-3PRGD2 uptake in primary lesion. α_vβ3 was significantly higher expressed in advanced stage than in early stage. ^99mTc-3PRGD2 uptake was consistent with microvessel density in the . Conclusions ^99mTc-3PRGD2 SPECT/CT showed high efficacy not only in detection of primary lesions but in lymph node and bone metastasis. Expression of α_vβ3 both in neovasculatures and tumor cell contributed to tumor uptake, α_vβ3 was significantly higher expressed in NSCLC or advanced stage compared with SCLC or early stage. RGD imaging served as a valuable tool for quantitation of αvβ3 level and evaluation of , it might be a surrogate for phenotyping and prognosis in lung cancer.