Purpose: Preclinical studies often compare micro-computed tomography (micro-CT) imaging with histology using optical microscopy of fluorescently labeled slides. However, correlating the images is difficult because the tissues appear differently in the two modalities. It would be valuable to have a single contrast medium visible on both radiographic and optical imaging.
Approach: We have explored the detectability of fluorescently labeled gold nanoparticles under micro-CT and optical projection tomography (OPT) in agarose phantoms and a murine melanoma tumor model. Murine melanoma cells were used to induce tumor growth in the right hind legs of 12 C57Bl6 mice, with the maximal tumor size of 1 cm3. We injected Cy3 fluorescently coated gold nanorods directly into the tumors. The mice were scanned with in vivo micro-CT (for pre- and post-contrast scans). Once euthanized, the hind leg was dissected and scanned with a higher resolution specimen micro-CT and OPT.
Results: The distribution of the gold nanoparticles appeared to be contained and isolated to the tumor. Alignment of micro-CT specimen scans with the OPT scans was possible, although there was also autofluorescence of the surrounding muscle tissue.
Conclusions: This study highlights the potential use of fluorescently labeled gold nanoparticles for imaging murine melanoma tumors using micro-CT and OPT.
Contrast agents are required to view and differentiate soft tissue structures in computed tomography (CT) yet in research, histology is still considered to be the gold standard. Preclinical contrast agents used for radiographic imaging are not visible when viewed histologically, nor are histological stains visible radiographically. By identifying a single agent that is visible in both x-ray and optical imaging, we can ensure that the target tissues can be easily identified and correlated in both images, without the need of additional staining techniques. Here we present an approach to allow for the correlation of imaging murine melanoma tumours using micro-computed tomography (micro-CT) and optical projection tomography (OPT), using fluorescently-labelled gold nanoparticles without additional tissue staining. B16F10 cells (murine melanoma cell line) were used to induce tumour growth in the right hind legs of twelve C57Bl6 mice. Tumor growth times varied between 2-3 weeks, with maximal tumor size of 1 cm3. We injected Cy3 fluorescently coated gold nanorods directly into the tumours. The mice were scanned with in vivo micro-CT (for pre- and post-contrast scans at a resolution of 50 microns) and once euthanized and hind leg dissected, further scanned with a specimen micro-CT at a higher resolution of 10-17.2 microns. Results showed that the distribution of the gold nanoparticles appeared to be contained and isolated to the murine melanoma tumour, allowing for contrast and visualization. Correlation of micro-CT specimen scans with optical projection tomography (OPT) imaging was possible, although there was also auto-fluorescence of the surrounding muscle tissue and melanoma cells. This study highlights the potential use of fluorescently-labelled gold nanoparticles as a dual-contrast agent for radiographic imaging of murine melanoma tumours using micro-CT and optical imaging using OPT.