A Pilot Study Imaging Integrin αvβ3 With RGD PET/CT In Suspected Lung Cancer Patients

Purpose: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, 18F-AL-NOTA-PRGD2, denoted as 18F-alfatide, has been developed for positron emission tomography (PET) imaging of integrin avP3. This is a pilot study to test the safety and diagnostic value of 18F-Arginine-Glycine-Aspartic (RGD) PET/CT in suspected lung cancer.Methods:Twenty-six patients with suspected lung cancer on enhanced CT underwent RGD PET/CT examination before surgery and puncture biopsy. Standard uptake values (SUV) and the tumour-to-blood ratio were measured and the diagnosis was pathologically confirmed.Results:RGD PET/CT with 18F-alfatide was performed successfully in all patients and no clinically significant adverse events were observed.The 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 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 ROC curve was 0.75 (P=0.038), and ROC analysis suggested a 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 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 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, positive predictive value, and negative predictive value of PET/CT for lymph nodes was 92.86%,95.65%,95.40%,61.90%, and 99.25%, respectively.Conclusion:Our results suggest that RGD PET/CT with the new tracer 18F-alfatide is safe and potentially effective in the diagnosis in 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 fin dings.