99mTc-Galacto-RGD2 Integrin αvβ3 Targeted Imaging as a Surrogate for Molecular Phenotyping in Lung Cancer: Prospective Study in the Real World

Abstract Purpose: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of 99mTc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, Integrin αvβ3 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 prostective study from January 2013 to December 2016. All patients underwent 99mTc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of 99mTc-Galacto-RGD2 was measured as the tumour/normal tissue ratio（T/N）. The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour tissues were obtained from 66 patients with malignant diseases and seven with benign disease. Tumour expression levels of αvβ3, CD31, Ki-67, and CXCR4 were analysed to determine their value for phenotyping and metastasis potential evaluation. 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 99mTc-Galacto-RGD2 SPECT/CT using a cut-off value of 2.5 were 91.89 %, 48.0 %, and 86.67 %, respectively. Integrin αvβ3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvβ3 expression. Integrin αvβ3 expression levels were significantly higher in advanced (Ⅲ, Ⅳ) than early stages (Ⅰ, Ⅱ). However, there was no significant correlation between tumour uptake and αvβ3 expression. Conclusion: 99mTc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer. RGD imaging may help evaluate the biological behaviour and phenotyping, and thus aid management in lung cancer.

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[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data

EJNMMI Research ◽

10.1186/s13550-021-00801-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jingjing Fu ◽

Yan Xie ◽

Tong Fu ◽

Fan Qiu ◽

Fei Yu ◽

...

Keyword(s):

Lung Cancer ◽

Single Photon ◽

Characteristic Curve ◽

Photon Emission ◽

Primary Lung Cancer ◽

Emission Computed Tomography ◽

Real World Data ◽

Ki 67 ◽

Expression Levels ◽

Tumour Uptake

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [99mTc]Tc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αvβ3 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 [99mTc]Tc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [99mTc]Tc-Galacto-RGD2 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 αvβ3, 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 [99mTc]Tc-Galacto-RGD2 SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αvβ3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvβ3 expression. Integrin αvβ3 expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αvβ3 expression. Conclusions [99mTc]Tc-Galacto-RGD2 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.

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