Preclinical shortwave infrared tumor screening and resection via pHLIP ICG under ambient lighting conditions

There is a critical need to improve optical imaging that will lead to its widespread acceptance for routine clinical procedures. Shortwave infrared (SWIR, 900–1700nm) imaging has demonstrated clear advantages over visible and near-infrared imaging (reduced autofluorescence with improved contrast, resolution, and sensitivity at tissue depth). Here we show that the previously reported compound, pH low insertion peptide (pHLIP) conjugated to indocyanine green (ICG, pHLIP ICG) currently in clinical trials, serves as an excellent candidate for SWIR imaging protocols. SWIR’s increased sensitivity enabled preclinical tumor screening and resection at exposure times as low as 0.1 ms with acceptable signal-to-noise and contrast-to-noise ratios. Imaging was performed under ambient lighting conditions, and SWIRs sensitivity enabled an extended surgical resection window up to 96 hrs post injection in an orthotopic breast cancer mouse model. This work provides a direct precedent for the clinical translation of SWIR pHLIP ICG imaging for cancer resection. One Sentence Summary SWIR imaging under ambient lighting is highly sensitive to pHLIP ICG, a cancer targeting fluorescent agent currently under clinical investigation. ### Competing Interest Statement J.S.L. is a founder of pHLIP, Inc. has shares in the company, and the company has provided funding for previous manufacturing of pHLIP ICG, safety, pharmacology, and toxicology studies. J.S.L. also has shares in Stryker Corp. pHLIP ICG was donated by pHLIP, Inc for this study. The remaining authors declare no competing interests.