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

Jingjing Fu; Yan Xie; Tong Fu; Fan Qiu; Fei Yu; Wei Qu; Xiaochen Yao; Aiping Zhang; Zhenhua Yang; Guoqiang Shao; Qingle Meng; Xiumin Shi; Yue Huang; Wei Gu; Feng Wang

doi:10.1186/s13550-021-00801-x

[^99mTc]Tc-Galacto-RGD₂ integrin α_vβ₃-targeted imaging as a surrogate for molecular phenotyping in lung cancer: real-world data

EJNMMI Res. 2021 Jun 13;11(1):59. doi: 10.1186/s13550-021-00801-x.

Authors

Jingjing Fu^#¹, Yan Xie^#¹, Tong Fu^#², Fan Qiu¹, Fei Yu¹, Wei Qu¹, Xiaochen Yao¹, Aiping Zhang³, Zhenhua Yang⁴, Guoqiang Shao¹, Qingle Meng¹, Xiumin Shi¹, Yue Huang⁵, Wei Gu⁶, Feng Wang⁷

Affiliations

¹ Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.
² Department of Imaging, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
³ Department of Thoracic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
⁴ Department of Respiratory, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.
⁵ Department of Pathology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. huangyuexxy@163.com.
⁶ Department of Respiratory, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. guw2001@126.com.
⁷ Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China. fengwangcn@hotmail.com.

^# Contributed equally.

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 α_vβ₃ 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 α_vβ₃, 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 α_vβ₃ expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin α_vβ₃ expression. Integrin α_vβ₃ expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and α_vβ₃ 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.

Keywords: Angiogenesis; Biological behaviour; Integrin αvβ3; Lung cancer; [99mTc]Tc-Galacto-RGD2.

Abstract

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