Breast Cancer Research (Mar 2025)
Preclinical evaluation of 64Cu-labeled cetuximab in immuno-PET for detecting sentinel lymph node metastasis in epidermal growth factor receptor-positive breast cancer
Abstract
Abstract Background Despite advances in breast cancer imaging, reliable detection of sentinel lymph node (SLN) metastasis remains challenging. This study aimed to determine the ability of immuno-positron emission tomography (PET) using 64Cu-labeled cetuximab to detect SLN metastasis in a model of epidermal growth factor receptor (EGFR)-positive breast cancer. Methods The SLN metastasis model was established using the EGFR-strongly-expressing MDA-MB-468 breast cancer cell line. In this xenograft model, [64Cu]Cu-PCTA-cetuximab was administered intravenously (5.8 ± 0.9 MBq; n = 12) or both intradermally and subdermally into the parapapillary region of the tumor-containing mammary gland (4.3 ± 0.4 MBq; n = 11), after which PET was performed. 18F-FDG PET was also performed intravenously (9.1 ± 1.4 MBq; n = 4) or intradermally/subdermally (5.4 ± 2.2 MBq; n = 3) in the same cohort before [64Cu]Cu-PCTA-cetuximab PET. PET/computed tomography was performed 60 min after administration of 18F-FDG and 24 h after administration of [64Cu]Cu-PCTA-cetuximab. Delayed PET/CT scans were conducted 48 h after administration for all mice in the intradermally/subdermally administered [64Cu]Cu-PCTA-cetuximab group and for four of the 12 mice in the intravenously administered [64Cu]Cu-PCTA-cetuximab group. SLNs were identified using blue dye, and PET and pathological evaluations of the resected SLN were performed to confirm metastases. Results After intravenous administration of [64Cu]Cu-PCTA-cetuximab (n = 12), accumulation was detected in the primary tumor in all mice and in the axilla of eight mice (67%, SUVmax 1.24 ± 0.51), all of which were found to have SLNs with histologically confirmed metastasis. The sensitivity, specificity, accuracy, and negative and positive predictive values for PET with intravenously administered [64Cu]Cu-PCTA-cetuximab were 89%, 100%, 92%, 75%, and 100%, respectively. In contrast, all mice with intradermal/subdermal administration (n = 11) showed high accumulation in both the primary tumor and axillary lymph nodes (SUVmax 4.28 ± 1.19), with six mice (55%, SUVmax 5.01 ± 1.12) having histologically confirmed metastasis. The sensitivity, specificity, accuracy, and positive predictive values for PET with intradermally/subdermally administered [64Cu]Cu-PCTA-cetuximab were 100%, 0%, 55% and 55%, respectively. SLN metastasis was not detectable by intravenous or intradermal/subdermal 18F-FDG PET. Conclusions PET with intravenously administered [64Cu]Cu-PCTA-cetuximab demonstrated high precision for diagnosis of SLN metastasis in a xenograft model of EGFR-positive human breast cancer. Although further evaluation is necessary, intradermal/subdermal administration could be a useful therapeutic approach owing to its high accumulation in SLNs.
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