Feasibility of differentiating the HER2 status of primary breast tumors and metastatic axillary lymph nodes using synthetic targeted molecules

Background. Breast cancer is the most common cancer and the leading cause of cancer mortality among women. Determination of the molecular subtype is a key step in selecting the appropriate treatment strategy. Despite the standardization of current diagnostic methods, the risk of diagnostic errors remains significant, highlighting the need for noninvasive technologies that enable simultaneous assessment of tumor extent and HER2 expression.

The purpose of study was to evaluate the feasibility of anatomical visualization and determination of the HER2 receptor status of primary breast tumors and malignant axillary lymph nodes (mAlN) using [^99mTc]Tc-ADAPT6.

Material and Methods. The study included 40 patients with T2−4N1−3M0 breast cancer before starting systemic treatment. All patients underwent morphological and iHC studies of HER2 expression in tumors and mAlN (25 patients with positive and 15 patients with negative HER2 status). The patients were injected with 500 µg of [^99mTc]Tc-ADAPT6 followed by SPECT/CT imaging 2 hours after injection. The accumulation of [^99mTc]Tc-ADAPT6 was assessed by measuring the SUV_max in the primary breast tumor and the contralateral breast (background), as well as in mAlN and contralateral axillary region (background), the liver, the latissimus dorsi muscle (lDM) and the spleen. Tumor-to-reference organ and mAlN-to-reference organ ratios were also measured. Statistical data was calculated using Prism 10.2 for Windows.

Results. The findings demonstrated the feasibility of assessing locoregional disease extent and HER2 receptor status in the primary breast tumor and metastatic axillary lymph nodes using the radiopharmaceutical [^99mTc]Tc-ADAPT6. The tumor-to-lDM ratio ≥11.46 relative units was the most informative parameter for differentiating HER2-positive from HER2-negative status in primary tumors (80 % sensitivity and 86 % specificity, p<0.0001). For metastatic axillary lymph nodes, the most informative parameters were the mAlNto-lDM ratio ≥4.470 relative units (p<0.0001) and the mAlN-to-spleen ratio ≥1.196 relative units (p<0.0001) with 88 % sensitivity and 86.67 % specificity.

Conclusion. The use of [^99mTc]Tc-ADAPT6 in breast cancer patients enables assessment of locoregional disease extent and discrimination between HER2-positive and HER2-negative status in the primary tumor and metastatic axillary lymph nodes.

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