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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Ling
L
Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, China.
Hu
Man
M
Yu
Jin-ming
JM
Yang
Guo-ren
GR
Guo
Hong-bo
HB
Gao
Yan
Y
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015609:Organotechnetium Compounds; D010091:Oximes; D011446:Prospective Studies; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015609:Organotechnetium Compounds; D010091:Oximes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime