Integrin Imaging with99mTc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non–Small Cell Lung Cancer

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 αvβ3 expression 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 both 99mTc-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 χ2 analysis were used to compare the diagnostic performance of the two imaging methods. Results 99mTc-3PRGD2 SPECT/CT was found to be more specific than 18F-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 of 99mTc-3PRGD2 was found in positive correlation with the integrin αvβ3 expression (r = 0.84, P = .001) and microvessel density (r = 0.63, P = .011) in the tumors. Conclusion 99mTc-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