In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of Zr-pertuzumab PET/CT for human epidermal growth factor receptor 2 (HER2)-targeted imaging in patients with HER2-positive breast cancer. Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an institutional review board-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with Zr. Patients underwent PET/CT with 74 MBq ofZr-pertuzumab in a total antibody mass of 20-50 mg of pertuzumab. PET/CT, whole-body probe counts, and blood drawing were performed over 8 d to assess pharmacokinetics, biodistribution, and dosimetry. PET/CT images were evaluated for the ability to visualize HER2-positive metastases. Six patients with HER2-positive metastatic breast cancer were enrolled and administeredZr-pertuzumab. No toxicities occurred. Dosimetry estimates from OLINDA demonstrated that the organs receiving the highest doses (mean ± SD) were the liver (1.75 ± 0.21 mGy/MBq), the kidneys (1.27 ± 0.28 mGy/MBq), and the heart wall (1.22 ± 0.16 mGy/MBq), with an average effective dose of 0.54 ± 0.07 mSv/MBq. PET/CT demonstrated optimal imaging 5-8 d after administration. Zr-pertuzumab was able to image multiple sites of malignancy and suggested that they were HER2-positive. In 2 patients with both known HER2-positive and HER2-negative primary breast cancers and brain metastases,Zr-pertuzumab PET/CT suggested that the brain metastases were HER2-positive. In 1 of the 2 patients, subsequent resection of a brain metastasis proved HER2-positive disease, confirming that the Zr-pertuzumab avidity was a true-positive result for HER2-positive malignancy. This first-in-human study demonstrated safety, dosimetry, biodistribution, and successful HER2-targeted imaging with Zr-pertuzumab PET/CT. Potential clinical applications include assessment of the HER2 status of lesions that may not be accessible to biopsy and assessment of HER2 heterogeneity.

Eighteen years ago, the EORTC PET criteria standardized for the first-time response assessment by FDG PET. Response assessment by FDG PET has been further developed and refined by PERCIST (PET response criteria in solid tumors). This review describes the data underlying these two systems for assessing tumor response on FDG PET/CT. It also summarizes recent clinical studies that have compared EORTC criteria and PERCIST with each other as well as with the anatomically based “response criteria in solid tumors” (RECIST). These studies have shown that response assessment by EORTC criteria and PERCIST leads to very similar response classifications. In contrast, there are significant differences between response assessment by PERCIST and RECIST. Preliminary data also suggest that response assessment by PERCIST is better correlated with patient outcome and may be a better predictor for the effectiveness of new anti-cancer therapies than RECIST. If correct, this could have a significant impact on oncologic drug development. However, confirmation of the better predictive value of response assessment by PERCIST by data from randomized trials is still lacking.

USPIO-enhanced MR imaging appears valuable for assessment of axillary lymph node metastases in patients with breast carcinomas and is superior to nonenhanced MR imaging.

The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image-guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer. The Oncologist 2020;25:e231-e242Implications for Practice: The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.The Oncologist 2020;25:e231-e242 www.TheOncologist.com Breast Cancer Figure 7. Radiomics workflow. Reprinted by permission from Springer Nature, from Han et al., Radiomic nomogram for prediction of axillary lymph node metastasis in breast cancer. European Radiology 2019;7:3820-3829 [76].