Exploring the potential of contrast agents in breast cancer echography: current state and future directions

Abstract

Breast cancer stands as the most frequent malignancy and leading cause of death among women. Early and accurate detection of this pathology represents a crucial factor in enhancing both incidence and mortality rates. Ultrasound (US) examination has been extensively adopted in clinical practice due to its non-invasiveness, affordability, ease of implementation, and wide accessibility, thus representing a valuable first-line diagnostic tool for the study of the mammary gland. In this scenario, recent developments in nanomedicine are paving the way for new interpretations and applications of US diagnostics, which are becoming increasingly personalized based on the molecular phenotype of each tumor, allowing for more precise and accurate evaluations. This review highlights the current state-of-the-art of US diagnosis of breast cancer, as well as the recent advancements related to the application of US contrast agents to the field of molecular diagnostics, still under preclinical study.

Keywords: Breast cancer; Microbubbles; Neoangiogenesis; Ultrasound contrast agents.

Fig. 1

(left) Under normoxic conditions, the 1α subunit is produced and degraded in the intracellular environment. (right) Under hypoxic conditions, the degradation of HIF-1α is blocked, allowing its accumulation and translocation into the nucleus where it associates with the 1β subunit to become an active transcription factor

Fig. 2

VEGFR2 is a tyrosine kinase receptor composed of a small transmembrane region, an intracellular portion, and an extracellular portion with seven immunoglobulin-like domains. Activation of the receptor stimulates the proliferation and motility of ECs, leading to the formation of new blood vessels and increased vascular permeability

Fig. 3

Schematic representation of a microbubble, including examples of various outer shells and inner gas contents

Fig. 4

Specific molecular ligands of microbubbles: antibodies, peptides, proteins, natural scaffolds, or engineered scaffolds

Fig. 5

Scheme of a BR55 molecule. The inner gas core is surrounded by a phospholipid shell. The ligand consists of a heterodimeric peptide whose target is represented by the KDR insert of VEGFR-2, bound to the phospholipid shell through a PEGylated chain

Fig. 6

Molecular schematic representation of (from left to right) microbubbles, nanobubbles, and phase-change contrast agents