[Tc]Tc-Galacto-RGD integrin αβ-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [Tc]Tc-Galacto-RGD single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αβ expression, and neovascularization in lung cancer subtypes was also addressed.

Methods: A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [Tc]Tc-Galacto-RGD imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [Tc]Tc-Galacto-RGD was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αβ, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours.

Results: The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [Tc]Tc-Galacto-RGD SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αβ expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αβ expression. Integrin αβ expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αβ expression.

Conclusions: [Tc]Tc-Galacto-RGD SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.