Figure 4. Differential niche-based accumulation of ReANC and fReANC formulations leads to multi-organ detection of metastases in a luminal breast cancer model.

(a) Athymic nude mice were injected with MCF7 derived cells via the left ventricle to form¹⁵ metastases in adrenals and bones; (b) Weekly intravenous administration of fReANCs show earlier detection of adrenal metastases compared to untargeted ReANCs. Quantitative analysis of SWIR intensity shows significantly higher accumulation of fREANCs compared to ReANCs at 5 weeks post inoculation whereas comparison between healthy controls and tumor-bearing animals injected with fReANC shows higher SWIR signal from adrenal lesions as early as 3 weeks post inoculation. Volumetric MRI analysis found the smallest tumor volume detected 5-weeks post inoculation with fReANCs to be 7.8 mm³, compared to a volume of 15.7 mm³ with REANCs. Representative dorsal (prone) images showing SWIR signal from adrenal lesions of healthy controls (c) and tumor-bearing animals injected with fReANC (d) and ReANC(e) shows earlier detection of adrenal metastases with active targeting. Data in (b) is expressed as mean±S.D; n=6 for tumor-bearing group and n=3 for healthy control group. *two-tailed P<0.05, determined by Welch’s t-test. ** two-tailed P<0.05, determined by Welch’s t-test. SWIR intensities were normalized to those of the healthy control groups for the region of interest at each time point.