Radionuclide-Based Imaging of Breast Cancer: State of the Art

Abstract

Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

“…Owing to inter- and intra-tumoral heterogeneity and sampling dependence, however, biopsies cannot accurately assess tumor phenotype and involve an invasive examination that limits their application. Radionuclide imaging is a highly sensitive non-invasive visualization tool that can address this challenge [ 20 , 21 ]. Immuno-single photon emission computed tomography (SPECT) and immuno-positron emission tomography (PET) applies radiolabelled monoclonal antibodies and derivatives as tracers for imaging, and can visualize biomarker distribution and detect expression levels in vivo [ 22 – 27 ].…”

Technological advancements in cancer diagnostics: Improvements and limitations

“…PSMA PET scans that utilize radioactive tracer labeled with galium or fluorine targeting this specific enzyme have been shown to have high sensitivity when used for prostate cancer screening, even when PSA levels are low. Enhanced amino acid synthesis is one of the indicator of extensive proliferation of cancer cells, therefore PET imaging agent L‐methyl‐11C‐methionine (11‐C‐MET) which measures methionine accumulation has been used in breast cancer patients, glioma, and leptomeningeal metastases 36–39 . Due to the rapid metabolism and short half‐life of 11‐C‐MET has limited the clinical utility and has posed time constraint on PET‐imaging, compromising the image acquisition and quality.…”

“…18F‐FACBC has been shown to be a better PET imaging agent for prostrate tumor due to its slow metabolism that prevents its rapid accumulation in the urinary bladder 40 . Thymidine analogs such as 11C‐thymidine, 3′‐deoxy‐3‐18fluorothymidine (18F‐FLT), and 1‐(2′‐deoxy‐2′‐fluoro‐1‐β‐D‐arabinofuranosyl)‐thymine (FMAU) imaging are used to measure the proliferation of tumor cells, targeting the thymidine uptake during DNA synthesis, suggesting the prognosis and aggressiveness of a tumor 39,41 . 18F‐labeled nitroimidazoles and Cu‐labeled diacetyl‐bis (N4‐methylthiosemicarbazone) analogs PET‐imaging has been utilized to measure hypoxia, implicating in determining the resistance of tumor to radio‐chemo‐therapy 42 .…”

Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review

“…Despite this correlation, there are some limitations that need to be taken into account, such as the lower uptake gradient of [ 18 F]F-FLT compared to [ 18 F]F-FDG into BC lesions (with potential false negative results) and its high uptake into liver and bone marrow (with potential disadvantages for lesion detection in these organs) ( 54 , 63 ). Although [ 18 F]F-FLT is absorbed to a lesser extent than [ 18 F]F-FDG in inflammatory tissue, leading to less false positives ( 64 ), the use of [ 18 F]F-FLT PET/CT for staging has been discouraged by these issues.…”