[99mTc]Tc-Galacto-RGD2 integrin αvβ3-targeted imaging as a surrogate for molecular phenotyping in lung cancer:
Jingjing Fu1, Yan Xie1, Tong Fu2
1Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.
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.
Insights
This study shows that technetium Tc 99m Galacto-RGD2 SPECT/CT imaging is highly sensitive for detecting lung cancer. However, its specificity is limited, with uptake influenced by integrin expression and neovascularization.
Area of Science:
- Nuclear medicine
- Oncology
- Radiopharmaceuticals
Background:
- Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are established treatments for lung cancer.
- Integrin αvβ3 plays a role in tumor neovascularization and is a target for cancer therapy.
- The diagnostic potential of [99mTc]Tc-Galacto-RGD2 SPECT/CT in lung cancer requires further investigation.
Purpose of the Study:
- To evaluate the clinical utility of [99mTc]Tc-Galacto-RGD2 SPECT/CT for detecting primary lung cancer.
- To assess the correlation between [99mTc]Tc-Galacto-RGD2 uptake and integrin αvβ3 expression and neovascularization in lung cancer subtypes.
- To analyze the relationship between imaging findings and clinicopathological features of lung cancer.
Main Methods:
- A prospective study involving 185 lung cancer patients and 25 patients with benign lung diseases.
- [99mTc]Tc-Galacto-RGD2 SPECT/CT imaging was performed on all participants.
- Tumor uptake was quantified as the tumor/normal tissue (T/N) ratio, and diagnostic efficacy was assessed using ROC analysis. Tumor specimens were analyzed for integrin αvβ3, CD31, Ki-67, and CXCR4 expression.
Main Results:
- [99mTc]Tc-Galacto-RGD2 SPECT/CT demonstrated a sensitivity of 91.89%, specificity of 48.0%, and accuracy of 86.67% for lung cancer detection.
- Integrin αvβ3 expression was higher in non-small cell lung cancer (SCLC) than SCLC, and squamous cell carcinoma showed increased neovascularization and integrin αvβ3 expression.
- Higher integrin αvβ3 expression was observed in advanced stages (III, IV) compared to early stages (I, II), but no significant correlation was found between tumor uptake and αvβ3 expression.
Conclusions:
- [99mTc]Tc-Galacto-RGD2 SPECT/CT exhibits high sensitivity but limited specificity for diagnosing primary lung cancer.
- Tumor uptake of [99mTc]Tc-Galacto-RGD2 is influenced by integrin expression on tumor vessels and cell membranes.
- Further research is needed to improve the specificity of this imaging modality for lung cancer detection.
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