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

Abstract

There is a critical need to improve optical imaging that will lead to its widespread acceptance for routine clinical procedures. Shortwave infrared (SWIR, 900 to 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. SWIRs 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.