Differential diagnosis of solitary pulmonary nodules using super(99m)Tc-3P sub(4)-RGD sub(2) scintigraphy

• Published in: European journal of nuclear medicine and molecular imaging 2011-12, Vol.38 (12), p.2145-2152
• Main Authors: Ma, Qingjie, Ji, Bin, Jia, Bing, Gao, Shi, Ji, Tiefeng, Wang, Xueju, Han, Zhenguo, Zhao, Guoqing
• Format: Article
• Language: English
• Subjects: Angiogenesis; Benign; Computed tomography; Differential diagnosis; Differentiation; Immunohistochemistry; Integrins; Lung nodules; Nodules; Nuclear medicine; Scintigraphy; Single photon emission computed tomography; Thorax; Tracers
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-011-1901-2

Purpose: Targeting of integrin alpha sub( nu ) beta sub(3) with molecular imaging agents offers great potential in early detection and monitoring of tumour angiogenesis. Recently, an RGD (Arg-Gly-Asp) tracer, super(99m)Tc-3P sub(4)-RGD sub(2), with high affinity to integrin alpha sub( nu ) beta sub(3) and in vivo tumour uptake was developed. In this study, we evaluate the feasibility of this novel radiotracer in the noninvasive differentiation of solitary pulmonary nodules (SPNs). Methods: Twenty-one patients with SPNs on CT were studied scintigraphically after administration of super(99m)Tc-3P sub(4)-RGD sub(2) with a dose of 939 plus or minus 118 MBq. Image interpretation using a 5-point scale was performed by one thoracic radiologist for CT and three nuclear medicine radiologists for single photon emission computed tomography (SPECT). Scintigraphic images were also analysed semiquantitatively by calculating tumour to normal tissue ratio (T/N). The "gold standard" was based on the histopathological diagnosis of the surgical samples from all recruited patients. A fraction of the samples were analysed immunohistochemically for integrin alpha sub(v) beta sub(3) expression. Results: Among the 21 SPNs, 15 (71%) were diagnosed as malignant and 6 (29%) were benign. The mean size for SPNs was 2.2 plus or minus 0.6 cm. The sensitivity and specificity for CT interpretation, SPECT visual and semiquantitative analysis were 80/67%, 100/67% and 100/67%, respectively. All SPNs classified as indeterminate by CT were correctly diagnosed by super(99m)Tc-3P sub(4)-RGD sub(2) scintigraphy. The empirical receiver-operating characteristic (ROC) areas were 0.811 [95% confidence interval (CI) 58-95%] for CT, 0.833 (95% CI 61-96%) for SPECT and 0.844 (95% CI 62-96%) for T/N ratios, respectively. Immunohistochemistry confirmed alpha sub( nu ) beta sub(3) expression in malignant and benign nodules with uptake in super(99m)Tc-3P sub(4)-RGD sub(2) scintigraphy. Conclusion: In this first-in-human study, we demonstrated the feasibility of using super(99m)Tc-3P sub(4)-RGD sub(2) scintigraphy in differentiating SPNs. This procedure appears to be highly sensitive in detection of malignant SPNs. SPECT visual analysis seems to be sufficient for characterization of SPNs.