⁶⁴CuS-labeled nanoparticles: a new sentinel-lymph-node-mapping agent for PET–CT and photoacoustic tomography

Determining sentinel lymph node (SLN) status is critical to cancer staging and treatment decisions. Currently, in clinical practice, ^99mTc-radiocolloid-mediated planar scintigraphy and single-photon emission computed tomography (SPECT) are used to guide the biopsy and resection of SLNs. Recently, an emerging technique that combines positron emission tomography (PET) and photoacoustic tomography (PAT; PET–PAT) may offer accurate information in detecting SLNs. Herein, we report a kind of ⁶⁴CuS-labeled nanoparticle (⁶⁴CuS-NP) for the detection of SLNs with PET–PAT. We subcutaneously injected ⁶⁴CuS-NPs into the rats’ forepaw pads. After 24 h, the rats’ first draining axillary lymph nodes (i.e. the SLNs) could be clearly visualized with micro-PET (μPET)–CT. Rats were sacrificed after μPET–CT imaging, their axillary lymph nodes were surgically identified, and then PAT was employed to discover ⁶⁴CuS-NP-avid SLNs, which were embedded inside tissues. Biodistribution, autoradiography, and copper staining analyses confirmed the SLNs’ high uptake of ⁶⁴CuS-NPs. Our study indicates that ⁶⁴CuS-NPs are a promising dual-function agent for both PET–CT and PAT and could be used with multi-modal imaging strategies such as PET–PAT to identify SLNs in a clinical setting.