Breast cancer is one of the most commonly diagnosed malignant tumors worldwide, possessing high incidence and mortality rates, which can be divided into five basic classes according to different molecular types, including luminal A, luminal B, HER2-enriched, basal-like, and normal-like.
As the most frequently used diagnosis approach, mammography can reduce 19% of breast cancer mortality which is recommended by the American Cancer Society beginning at age 45, or sooner depending on the individual physical health condition. Combined with digital breast tomosynthesis and a conventional full-field digital mammography examination can greatly reduce the false-positive results and increase cancer detection.
Ultrasounds are the major auxiliary imaging techniques, known as another most common method for diagnosis and monitoring response to therapy in breast cancer. The utilization of ultrasound is associated with various advantages, such as no ionizing radiation and high sensitivity, which have provided it a powerful diagnostic tool for the detection of breast tumors in young, pregnant, and breastfeeding women.
Magnetic resonance imaging (MRI) is another important diagnostic approach for breast cancer, as a supplementing mammography imaging modality, for various aspects of breast cancer management including monitoring of response to therapy, monitoring high-risk patients, assessment of breast cancer metastasis, and studies of tumor recurrence. It is found that MRI had a higher sensitivity for malignancy (84.6%) than mammography (38.6%) or ultrasound (39.6%), as well as a higher sensitivity for malignancy diagnosis by mammography with an auxiliary imaging tool by MRI (92.7%) than that of ultrasound (52%).
In clinical pathology diagnosis which can hardly distinct closely related diseases, diseased tissue is usually obtained by fine-needle aspiration, core biopsy, or surgical excision and is performed by microscopic evaluation and ancillary tests, such as immunohistochemistry (IHC), in situ hybridization, and molecular tests based on reverse transcription–polymerase chain reaction. Critical treatment decisions are made on the basis of molecular biology assessment of tumor markers, including protein expression assays to evaluate estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu (HER2) status, as well as DNA microarrays and high-throughput reverse transcription–polymerase chain reaction assays to categorize breast cancers into several prognostic groups.
Traditional diagnostic imaging, such as mammography, ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT), is largely based on detecting changes in the physical structure of tumors without additional information about the molecular characteristics of breast cancer at the early stage, which may lead to the inaccuracy of cancer diagnosis. The radionuclide-labeled molecule used in noninvasive visualization of imaging displays its advantages for detecting breast cancer from a functional perspective in the early and effective breast cancer diagnosis to enhance the survival rate.
Recently, a series of RDC (Radionuclide Drug Conjugate) have been used for noninvasive detection of HER2 overexpressed in breast cancer, such as 64Cu-Trastuzumab, 64Cu-DOTA-Zher2:477, 68Ga-DOTA-F(ab’)2-trastuzumab, 68Ga-ABY-002, and 89Zr-Trastuzumab, in which 68Ga-DOTA-F(ab’)2-trastuzumab applied in PET has bifunctional utilities, including diagnostic imaging and downregulation of HER2 associated with Hsp90 inhibition and 89Zr-Trastuzumab displayed an extremely high image quality in preclinical studies and obtained good spatial resolution and sensitivity.
Fig.1 Schematic overview of receptor-targeting molecular imaging for breast cancer.
(Li, H., et al., 2021, Cancers)
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