Next-generation Tissue-Adhesive Endoscopic Tattoo Ink

SUMMARY This Phase I STTR project aims to develop a lead candidate Tissue Adhesive Tattoos generation 2 (TAT2) ink to overcome the significant limitations of current commercial inks for endoscopic marking. The new ink will demonstrate excellent tissue retention (no diffusion), equivalent white-light contrast with Spot® Ex (the lead commercial competitor), and no inflammatory potential. Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States, as per 2023 statistics from the American Cancer Society, with an estimated 153,020 people receiving a diagnosis of CRC, leading to 52,550 deaths from the disease. Early identification and detection of the disease are crucial for saving lives, and more than eleven million colonoscopies and over 6 million upper GI endoscopies are conducted in the US annually. GI tattooing is a widely used clinical practice, and endoscopic lesion marking with tattoo ink is recommended by the US Multi-Society Task Force on Colorectal Cancer to mark suspect regions (e.g., polyps > 1cm) with tattoo inks to facilitate identification for longitudinal follow-up, surgery, or additional procedures at a different provider. The only FDA-approved ink, Spot® Ex (Laborie Medical Technologies), suffers from high diffusion in tissues, which leads to poor spot precision and localization, the generation of a fibrotic response in healthy tissues, extravasation and transmural diffusion to other tissues, and spillage into the peritoneal space leading to peritonitis. In earlier project development at Arizona State University (ASU), we have developed a library of TAT2 inks that demonstrate excellent tattoo performance over the commercial tattoo ink with no systemic inflammation and toxicity over a 14-day survival study in pigs and robust shelf-life stability for up to 3 months. In this proposal, Endotat Biotechnologies, LLC will initiate steps towards commercialization by developing an optimized, lead candidate TAT2 ink with enhanced control over particle size (less than 0.5 polydispersity), long-term shelf stability (at least four and up to six months), and efficient synthesis (room temperature and inert atmosphere) amenable to eventual scale-up. Using these optimized formulations, team members at ASU will evaluate the inflammatory response and effect on cell viability using cell-based in vitro assays and evaluate localization performance in an ex vivo assay in fresh porcine colon tissue. The lead candidate TAT2 ink performance will be further evaluated in live Yorkshire pigs during a long-term (6-month) survival study to performed under human clinical-equivalent endoscopy procedure conditions at Mayo Clinic in Arizona. Quantitative measures will be used to evaluate the ability of the ink to retain tight localization, avoid systemic and local toxicity, inflammatory response and fibrosis, and mitigate distribution and toxicity to other organs over six months. The results of this study will establish the foundation for the scaled development and regulatory determination of highly effective TAT2 inks that will dramatically enhance the performance of endoscopic marking, detection, and surveillance of colorectal diseases with clear potential benefit to patient care and a strong path towards commercial success.