Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy

PurposeTargeting of integrin ανβ3 with molecular imaging agents offers great potential in early detection and monitoring of tumour angiogenesis. Recently, an RGD (Arg-Gly-Asp) tracer, 99mTc-3P4-RGD2, with high affinity to integrin ανβ3 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).MethodsTwenty-one patients with SPNs on CT were studied scintigraphically after administration of 99mTc-3P4-RGD2 with a dose of 939 ± 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 αvβ3 expression.ResultsAmong the 21 SPNs, 15 (71%) were diagnosed as malignant and 6 (29%) were benign. The mean size for SPNs was 2.2 ± 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 99mTc-3P4-RGD2 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 ανβ3 expression in malignant and benign nodules with uptake in 99mTc-3P4-RGD2 scintigraphy.ConclusionIn this first-in-human study, we demonstrated the feasibility of using 99mTc-3P4-RGD2 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.

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