Objective:To investigate the value of imaging with 99Tcm-HYNIC-PEG4-E[PEG4-c(RGDfk)]2(99Tcm-3P4-RGD2) as radiotracer in the dectection of lung cancer bone metastases. Methods: A total of 45 patients (25 males and 20 females) with lung cancer were retrospectively studied in our hospital from July 2012 to September 2014. All patients received 99Tcm-3P4-RGD2 imaging (RGD imaging,including plane and tomography) and 99Tcm-MDP imaging(MDP imaging,including plane and tomography),meanwhile undergoing SPECT-CT fusion imaging. The final diagnosis was made based on history, pathology,and 6 months follow-up. RGD imaging in the diagnosis of lung cancer with bone metastasis lesions was investigated. Results:Within 122 bone metastasic lesions, 102 was osteolytic, 20 was osteoblastic metastases (5 were demonstrated no bone density changes)and there were 51 benign bone lesions. Regional accumulation of 99Tcm-3P4-RGD2 (T/NT:6.90 ± 2.31) was higher than that of 99Tcm-MDP (1.18 ± 1.24,P=0.010). The diagnotic sensitivity of RGD imaging to osteolytic metastases was 84.8%, higher than that of MDP imaging(25.0%) while the diagnostic sensitivity of RGD imaging to osteoblastic metastases was 55.9%, lower than that of MDP imaging(91.2%)(both P < 0.05). When combined with 6 slice-CT imaging, the diagnostic specificity difference of bone metastases between RGD fusion imaging and MDP fusion imaging was insignificant. The diagnostic sensitivity and accuracy of MDP fusion imaging(92.6% and 93.4%) were higher than those of RGD fusion imaging(78.7%,P=0.008;80.3%,P=0.010). Furthermore, RGD imaging also detected primary lung cancer and lymph node metastases. Conclusion: Specifically targeting integrin αvβ3, which was highly expressed on osteoclast and lung cancer cells,99Tcm-3P4-RGD2 imaging has great potential for detection of lung cancer osteolytic metastasis.