Radiotracer Innovations in Breast Cancer Imaging: A Review of Recent Progress

Abstract

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors and metastatic sites and the assessment of tumor response to therapy. In addition to ¹⁸F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Keywords: 18F-fluorodeoxyglucose; breast cancer; molecular imaging; nuclear medicine; positron emission tomography; radiopharmaceuticals; radiotracers; tumor detection.

Figure 1

¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) images of a 37-year-old woman with invasive ductal carcinoma of the right breast, showing an FDG-avid lesion in the right breast in keeping with the primary malignancy (a,b), as well as an FDG-avid right axillary lymph node, which is likely metastatic (a,c).

Figure 2

¹⁸F-FDG PET/CT images of a 77-year-old woman with metastatic left breast cancer. The images show a large FDG-avid lobulated necrotic mass in the outer aspect of the left breast, corresponding to the primary malignancy. There are enlarged FDG-avid metastatic left axillary and retropectoral lymph nodes, FDG-avid metastatic subcutaneous soft tissue deposits, and multiple innumerable intensely FDG-avid metastatic lytic bone lesions.

Figure 3

3′-deoxy-3′-[¹⁸F]-fluorothymidine (¹⁸F-FLT) positron emission mammography (PEM) images of a 47-year-old woman with left breast cancer. (a) Left mediolateral oblique (LMLO) view. (b) Left craniocaudal (CC) view.

Figure 4

⁶⁸Ga-Trivehexin positron emission mammography (PEM) images of a 57-year-old woman with left breast cancer. (a) Left mediolateral oblique (LMLO) view. (b) Left craniocaudal (CC) view.

Figure 5

¹⁸F-FDG and ⁶⁸Ga-fibroblast activation protein inhibitor-46 (⁶⁸Ga-FAPI-46) PET/CT images of a 74-year-old woman with invasive lobular carcinoma of the left breast. (a) Maximum intensity projection (MIP) whole-body PET/CT images. (b) ⁶⁸Ga-FAPI-46 PET/CT of the primary breast lesion. (c) ¹⁸F-FDG PET/CT of the primary breast lesion. (d) ⁶⁸Ga-FAPI-46 PET/CT of the metastatic hepatic lesions. (e) ¹⁸F-FDG PET/CT of the metastatic hepatic lesions. The images show faint ¹⁸F-FDG uptake in the left breast, increased ⁶⁸Ga-FAPI uptake in the upper central quadrant of the left breast, ⁶⁸Ga-FAPI-46 avid metastatic hepatic lesions, and ⁶⁸Ga-FAPI-46 avid pleural thickening in the right lower lobe of the lung (likely atelectatic).

Figure 6

Well-differentiated estrogen receptor (ER)-positive breast tumor with significantly less radiotracer uptake on ¹⁸F-FDG PET/CT than on 16α-[¹⁸F]fluoroestradiol (FES) PET/CT, with FES showing more sites of ER-positive disease. The images show FES-avid mediastinal lymph nodes and right iliac bone lesion (B,D,F,H; white arrows in FES images) with significantly less ¹⁸F-FDG uptake (A,C,E,G).

Figure 7

¹⁸F-FDG and FES PET/CT images of a 36-year-old woman diagnosed with breast cancer. The images from 2014 show matched lesions seen with both ¹⁸F-FDG and FES. The patient subsequently received multiple lines of hormone-targeted therapy. The images from 2016 after treatment show that FES was negative, but ¹⁸F-FDG avid metastatic lesions were detected in the lymph nodes, bones, and liver. The images show the gradual transformation from functional ER-positive to ER-negative tumors. These serial images show the paradigm transformation and hence an impact on management and treatment.