In Vivo Photoacoustic Detection of Lymph Node Metastasis using Glycol-Chitosan-Coated Gold Nanoparticles

Submitted by Diego Dumani, PhD Candidate, Georgia Institute of Technology.

Metastasis rather than primary tumors determine prognosis and mortality in the majority of cancer patients. Detection of metastatic lesions is critical to determine prognosis and suitable treatments. We developed a method for identifying sentinel lymph node (SLN) metastasis, using combined ultrasound and photoacoustic (US/PA) imaging augmented with glycol-chitosan-coated gold nanoparticles (GC-AuNP). Presence of metastasis affects accumulation of GC-AuNP in the SLN, which can be monitored via US/PA imaging.

We injected GC-AuNP peritumorally for drainage into the SLN of breast tumor-bearing mice. US/PA imaging of the SLN was performed before and immediately after the injection, and then 1 h, 24 h, and 48 h after the injection.  Accumulation of GC-AuNP in the LN after cellular uptake by immune cells (macrophages) was visualized using PA imaging in the near-infrared wavelength range. To quantify accumulation, we used spectroscopic PA (sPA) in the 680-970 nm wavelength range, which allowed for isolation of signal corresponding to GC-AuNP. 

US/PA imaging showed that accumulation of GC-AuNP in the SLN was reduced due to metastasis. While single-wavelength PA images demonstrated the effect qualitatively, the accumulation of GC-AuNP was quantified using sPA analysis. The overall sPA signal (area of sPA image relative to area of LN) within the lymph node was reduced by more than 20% compared to healthy controls. No changes were observed between 24 h and 48 h drainage. Histology confirmed that metastatic cells inside the SLN disturb the distribution of particles inside immune cells, stopping them from spreading across the SLN, as identified by US/PA. In healthy controls, GC-AuNP were found in macrophages across the lymph node. In conclusion, the developed US/PA imaging method can aid physicians in detection of micrometastasis thus guiding and avoiding unnecessary SLN biopsy.