Combination Imaging Method Tracks Where Nanomedicines Land

Researchers continue to develop nanoparticles to target drugs to tumors, while avoiding healthy organs. But they lack a reliable and inexpensive way to track how these particles accumulate in animal tissues. Now researchers have combined X-ray-based imaging with fluorescence imaging to spot where nanomedicines end up in mice (ACS Nano, DOI: 10.1021/nn303955n).

To check to see if drug-delivering nanoparticles accumulate mostly in tumor tissue, and not in organs such as the liver, scientists would like to quickly scan living mice to find the distribution of the particles. One option is fluorescence imaging. The technique is inexpensive and most laboratories have the necessary equipment. But most wavelengths of light don’t penetrate deeply into tissue. So to track the movement of nanomedicines, researchers often must kill the animals and study two-dimensional slices of their tissues. Another method, fluorescence molecular tomography (FMT), uses near-infrared light, which can penetrate through tissue. It can produce three-dimensional images of animals without killing them, but its resolution does not allow researchers to determine the amount of particle accumulation in individual organs.

To get a high resolution three-dimensional image, some researchers add radioactive labels to their particles and then scan the mice with positron emission transfer (PET) imaging. But PET instruments are expensive, and many academic laboratories aren’t certified to use radioactive compounds.

Twan Lammers and Fabian Kiessling of RWTH Aachen University, in Germany, and their colleagues looked at these existing techniques and realized that a better method would involve combining X-ray computed tomography (CT) with FMT. Computed tomography can distinguish organs within the body without contrast agents. The researchers wanted to use the CT images to define the boundaries of organs and then overlay them with FMT data to measure the distribution of the particles within each organ.

To test their proposed combination method, Lammers and his colleagues started by injecting mice with colon cancer cells. The cells grew into tumors within two weeks. After the tumors formed, the scientists injected the rodents with a fluorescently labeled nanoparticle made from the polymer poly(N-(2-hydroxypropyl)methacrylamide). The team performed CT scans on the mice and analyzed those images to delineate the boundaries of the animals’ organs and the tumors. Immediately after the CT scan, the scientists used FMT imaging to examine the distribution of the fluorescent dye. They then overlaid the two data sets to see which tissues had high levels of the nanoparticles. They compared these three-dimensional data with a series of two-dimensional images made from the animals’ organs. The combination technique produced similar results, without needing to kill the rodents.

In addition to keeping the mice alive, the combination method is fast: Lammers estimates that a researcher could scan 20 mice in a single day. With the ability to scan many mice in a short period, researchers can quickly evaluate drug delivery, he says.

Although this isn’t the first time scientists have combined CT and FMT, it’s the first method that researchers can easily adapt for use in their own lab, says Gang Zheng of the University of Toronto, in Canada. The combination method doesn’t completely replace PET, he says, but it would provide academic researchers, who don’t have easy access to PET scanners, a way to measure particle distribution in mice.