Abstract
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Purpose: This study aimed to investigate the value of 99mtechnetium (99mTc)-three polyethylene glycol spacers (3P)-arginine-glycine-aspartic acid (RGD) (99mTc-3PRGD2) imaging in breast cancer and its staging compared with 18F-FDG PET/CT; and to explore the expression of integrin αVβ3 in tumor vascular endothelial cells. Procedures: Forty-two women with suspected breast cancer participated in this prospective study. All patients underwent both 99mTc-3PRGD2 SPECT and 18F-FDG PET/CT before biopsy or treatment. Visual analysis was used to assess the primary breast lesion, axillary lymph node metastasis and distant metastasis. Semi-quantitative analysis of breast lesions was performed by using the tumor-blood (T/B) ratios from SPECT imaging and the maximum standardized uptake value (SUVmax) from PET/CT imaging. The histopathology was considered the “gold standard” reference. Integrin αvβ3in tumor vascular endothelial cells were analyzed through immunohistochemistry. Results: Forty-five breast lesions were founded in 42 patients (malignant, n = 38; benign, n = 7). The sensitivity, specificity and accuracy of 99mTc-3PRGD2 and 18F-FDG imaging in visual analysis for the primary breast lesion were 97.4%, 87.5%, and 95.6% and 97.4%, 71.4%, and 93.3%, respectively (P > 0.05). For semi-quantitative analysis, the diagnostic accuracy of SPECT and PET/CT were 86.8% (cut-off = 2.75 of T/B) and 91.1% (cut-off = 3.3 of SUVmax), respectively. The area under the curve (AUC) for PET/CT (AUC = 0.955) was not significantly higher than that for SPECT (AUC = 0.880) (Z = 0.88, P > 0.05). The sensitivity, specificity, accuracy for axillary lymph node metastasis for the two images were 78.05%, 99.36%, and 94.92% and 85.37%, 98.72%, and 95.64%, respectively (P > 0.05). Nine patients with distant metastases via comprehensive analysis from other examinations or follow-up were detected in two images. Integrin αvβ3 in tumor blood vessels was mainly expressed in microvascular endothelial cells. It was correlated with 99mTc-3PRGD2 uptake (r = 0.582, P = 0.001) and CD31 (r = 0.819, P = 0.000). Further, integrin αvβ3 expression of microvessels and 99mTc-3PRGD2 uptake were significantly higher in the HER2-positive and stage = 3 \[asterisk] ROMAN III - = 4 \[asterisk] ROMAN IV breast cancer patients (P < 0.05). Conclusions: The present study demonstrated that 99mTc-3PRGD2 SPECT imaging seems to be valuable for clinical diagnosis of breast cancer and its staging with suitable sensitivity, specificity and accuracy. When compared with 18F-FDG PET/CT imaging, it may be less sensitive for detecting lymph node metastasis. Integrin αvβ3 in tumor microvessels was associated with breast cancer subtype and its staging. Key words 99mTc-3PRGD2, breast cancer, 18F-FDG. Integrin αvβ3, microvessel