Sensitive and specific detection of breast cancer lymph node metastasis through dual-modality magnetic particle imaging and fluorescence molecular imaging: a preclinical evaluation

A sensitive and specific imaging method to detect metastatic cancer cells in lymph nodes to detect the early-stage breast cancer is still a challenge. The purpose of this study was to investigate a novel breast cancer-targeting and tumour microenvironment ATP-responsive superparamagnetic iron oxide nanoparticles (SPIOs) imaging probe (abbreviated as SPIOs@A-T) that was developed to detect lymph node metastasis through fluorescence molecular imaging (FMI) and magnetic particle imaging (MPI).The conjugation of the targeted peptide CREKA and SPIOs was via linker sulfo-SMCC, while the dsDNA-Cy5.5 was modified on SPIOs through the conjugation between maleimide group in sulfo-SMCC and sulfydryl group in dsDNA-Cy5.5. SPIOs@A-T was characterised for its imaging properties, targeting ability and toxicity in vitro. Mice with metastatic lymph node (MLN) of breast cancer were established to evaluate the FMI and MPI imaging strategy in vivo. Healthy mice with normal lymph node (NLN) were used as control group. Histological examination and biosafety evaluation were performed for further assessment.After injection with SPIOs@A-T, the obvious high fluorescent intensity and MPI signal were observed in MLN group than those in NLN group. FMI can specifically light up MLN using an ATP-responsive fluorescence design. On the other hand, MPI could complement the limitation of imaging depth from FMI and could detect MLN more sensitively. Besides, the biosafety evaluation results showed SPIOs@A-T had no detectable biological toxicity.SPIOs@A-T imaging probe in combination with FMI and MPI can provide a promising novel method for the precise detection of MLN in vivo.