Improved ink for colon tattoos

image: Commercial ink (left) diffuses away from injection sites (arrows) under mouse skin, but new colon tattoo ink (right) diffuses much less.
to see Continued

Credit: Jordan Yaron, Ph.D.

SAN DIEGO, March 22, 2022 – The colon might be the last place people would consider tattooing, but endoscopic tattooing is an important medical technique for marking colorectal lesions for surgery or follow-up. Now scientists are reporting a next-generation ink for these markings that scatters less and is more biocompatible than existing inks. According to the researchers, the new formulation could make it easier to identify and remove polyps and complex colon tumors.

They will present their findings today at the American Chemical Society (ACS) Spring Meeting. ACS Spring 2022 is a hybrid meeting that will be held virtually and in person March 20-24, with on-demand access available March 21-April 8. The meeting features more than 12,000 presentations on a wide range of scientific topics.

According to the American Cancer Society, colorectal cancer is the third most diagnosed cancer in the United States and the second leading cause of cancer death. March is Colorectal Cancer Awareness Month, when people over 50 are reminded to have a colonoscopy, or endoscopic examination of the colon, to check for cancerous and precancerous lesions. Small polyps can usually be removed at the time of colonoscopy; however, larger and more complex lesions are often referred to specialists or surgeons for later removal.

“Often they are very flat, very subtle lesions, and they need to be marked so that the specialist who visits later can find them,” says Rahul Pannala, MD, gastroenterologist and associate professor of medicine at the Mayo Clinic Arizona, which is participating in the research. To do this, doctors inject a commercial ink, usually made of carbon black, a few centimeters from the lesion – a process known as endoscopic or colon tattooing. “Commercial inks have high contrast, but once injected, they diffuse quickly around the spot area,” says Subhadeep Dutta, a grad student from Arizona State University who is presenting the work at the meeting. . “So the specialist may be lost as to where to find the lesion.” Additionally, some inks can trigger inflammation or diffuse into other tissues, possibly causing side effects.

Therefore, Dutta; Pannala; Jordan Yaron, Ph.D.; and Kaushal Rege, Ph.D. (Project Principal Investigator, Arizona State University), wanted to develop a new type of colon tattoo ink that could overcome these limitations. To give the ink a strong dark color that would be easy to see under the visible light of a colonoscopy, the researchers chose metal-derived nanoparticles. They combined the nanoparticles with different amounts and types of polymers that adhere to the submucosal surface of the colon, preventing the ink from diffusing.

They tested the different formulations, first on dissected pig intestines, then on live mice. Because mouse intestines are so small and difficult to work with, the researchers injected their inks under the skin of mice as a model system to assess diffusion, inflammation, and imaging efficiency. “Based on our preclinical studies so far, the contrast is good and our inkblots are really concentrated. At 28 days, they are at least three to four times smaller than the commercial dye’s flecks,” says Dutta. Although there are no obvious signs of inflammation, the team is currently performing histopathological studies to observe if any microscopic changes occur in the skin and to help determine the optimal ink formulation. also gearing up to test the best inks in real live pig endoscopic tattoos.

Another advantage of nanoparticles is that, unlike commercial inks, they should be visible on computed tomography (CT) imaging, although the researchers haven’t tested this yet. “Because the nanoparticles have X-ray CT contrast properties, in addition to being visible under endoscopic light, we believe the new inks could enable multimodal imaging,” says Rege. This could help doctors better characterize a lesion before surgery.

If the tattoo ink proves superior to existing formulations, the researchers say it could translate to better patient care. “This could lead to safer removal of complex polyps and tumors, and better identification in imaging scanners,” says Pannala. “And it’s not limited to colon cancer. If we are able to develop very precise ink, we could also use it to mark growths and tumors anywhere in the intestine, or even in the pancreas.

The researchers acknowledge support and funding from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.

A recorded press conference on this subject will be released on Tuesday, March 22 at 10:00 a.m. EST at www.acs.org/acsspring2022briefings.

ACS Spring 2022 will be a vaccination-mandated and mask-wearing event recommended for all ACS attendees, exhibitors, vendors and staff planning to attend in person in San Diego, CA. For detailed information on the requirement and all ACS security measures, please visit the ACS website.

The American Chemical Society (ACS) is a nonprofit organization accredited by the United States Congress. ACS’s mission is to advance the broader chemical enterprise and its practitioners for the benefit of the Earth and all its inhabitants. The Society is a global leader in promoting excellence in science education and access to chemistry-related information and research through its multiple search solutions, peer-reviewed journals, its scientific conferences, e-books and weekly periodicals. Chemistry and Engineering News. ACS journals are among the most cited, trusted and widely read in the scientific literature; however, the ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing global scientific knowledge. ACS’s principal offices are located in Washington, DC, and Columbus, Ohio.

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Note to Editors: Please note that this research was presented at a meeting of the American Chemical Society.

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Title
Formulation of composite inks based on biomaterials for endoscopic imaging application

Abstract
Endoscopic tattooing (or “colon tattooing”) is a widely used clinical technique to mark colorectal lesions for subsequent surgical resection or to facilitate follow-up of the endoscopic resection site. The technique involves injecting dark-colored (i.e. high-contrast) ink into the submucosal layer of the colon. Currently used inks, such as Spot-Ex® or Indian ink, are prone to many side effects such as peritonitis, abscess formation. Spot-Ex® diffuses rapidly and substantially throughout the submucosal tissue, making it difficult to match a tattoo to the desired lesion of interest. There is a significant and unmet need for new endoscopic tattoo inks that can (1) retain localization for improved tracking accuracy and (2) not induce toxic, inflammatory, or fibrotic responses. We generated novel biomaterial-based inks, formulated with (1) metal-derived nanoparticles (anionic iron oxide nanoparticles coated with dextran) as contrast agents and (2) mucoadhesive polymers (derived from cationic chitosan) as a bioprotective and retention coating. mediator carrier. By modulating the ratio of contrast agent to polymer coating, we have formulated a series of composite inks that have been tested ex-vivo in porcine intestinal tissue and demonstrate nearly equivalent contrast quantification to commercially available inks while also exhibiting significantly improved stain localization ability. Preclinical studies in mice using subcutaneous injections with composite ink indicate live efficacy for stain localization, contrast ability, and chemistry-dependent biocompatibility responses of biomaterials. These formulations represent a new generation of biocompatible endoscopic inks that will have measurable impacts on patient quality of life and procedural outcomes with a clear path to clinical translation.


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