Tc-99m-3PRGD2 is a new SPECT tracer targeting integrin alpha(V)beta(3) receptor for detecting tumors, imaging angiogenesis, and evaluating tumor response to therapy. A multicenter study was designed to investigate the efficacy of Tc-99m-3PRGD2 for the evaluation of patients with lung cancer. Methods: Seventy patients (51 men, 19 women; mean age +/- SD, 63 +/- 9 y) with a suspected lung lesion and for whom definite pathologic diagnosis was finally obtained (malignant, n = 58; benign, n = 12) were recruited from 6 centers. Whole-body planar scanning and chest SPECT were performed at 1 and 4 h, respectively, after intravenous injection of 11.1 MBq/kg (0.3 mCi/kg) of (99)mTc-3PRGD2. The images were read in consensus by 6 experienced nuclear medicine physicians masked to the source, history, and pathologic diagnosis. The tumor-to-background (T/B) ratios were calculated for semiquantitative analysis. A Student t test was used for statistical analysis, and a P value less than 0.05 was considered significant. Results: With low Tc-99m-3PRGD2 background in the lungs and mediastinum, most lung malignancies were prominent on the 1-h images (T/B ratio, 1.65 +/- 0.47 for the planar imaging and 2.78 +/- 1.52 for SPECT). The T/B ratios were significantly lower in the benign lesions (P < 0.05). The sensitivity was 88% for semiquantitative analysis and could reach 93%-97% in visual analysis when considering the volume effect, necrosis, and metastasis. However, the specificity was only 58%-67%. Most lymph node and bone metastases could also be detected. Conclusion: Tc-99m-3PRGD2 imaging at 1 h is sensitive for the detection of lung cancer, meriting further investigation of Tc-99m-3PRGD2 as a novel clinical tracer for integrin receptor imaging.