Correlations of 99 Tc m-HL91 SPECT hypoxia imaging with HIF-1alpha and VEGF expression in non-small cell lung cancer

Abstract

(99)Tc(m)-HL91 ((99)Tc(m) labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that (99)Tc(m)-HL91 has validity for hypoxia imaging in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the (99)Tc(m)-HL91 SPECT hypoxia imaging of NSCLC, the expression of inducible hypoxia factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF), and to analyze their correlations with clinicopathological characteristics. Twenty NSCLC patients who underwent radical resection were enrolled into this study prospectively. (99)Tc(m)-HL91 SPECT scanning was performed in all patients at one or two days before surgery. After intravenous injection of approximately 740 MBq (99)Tc(m)-HL91, anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. Immunohistochemistry was used to detect the expression of HIF-1alpha and VEGF in sequential histological sections of specimens. Among the 20 NSCLC patients, 13 showed positive expression of HIF-1alpha and 15 had positive expression of VEGF, with a positive rate of 65.0% and 75.0%, respectively. The uptake of (99)Tc(m)-HL91 was strongly correlated with the expression status of HIF-1alpha. No correlation between HIF-1alpha and VEGF expression levels was observed. The HIF-1alpha expression level was not correlated with histological subtype, but with lymph node involvement. The expression levels of HIF-1alpha and VEGF were positively correlated with tumor stage. The result of (99)Tc(m)-HL91 SPECT hypoxia imaging is found to be positively correlated with expression of HIF-1alpha in the non-small cell lung cancer. HIF-1alpha expression is positively correlated with VEGF expression. Furthermore, both HIF-1alpha and VEGF expressions are increasing with the increase of tumor stage.