Carbohydrate based biomarkers enable hybrid near infrared fluorescence and ⁶⁴Cu based radio-guidance for improved surgical precision

Abstract

Increasing numbers of lung tumors are identified at early disease stages by diagnostic imaging in screening programs, but difficulties in locating these during surgical intervention has prevented an improved treatment outcome. Surgical biomarkers that are visible on diagnostic images, and that provide the surgeon with real-time image guidance during the intervention are thus highly warranted to bridge diagnostic precision into enhanced therapeutic outcome. In this paper, a liquid soft tissue marker for near infrared fluorescence and radio-guidance is presented. The biocompatible marker is based on the carbohydrate ester, sucrose acetate isobutyrate, ethanol, and a multifunctional naphthalocyanine dye, which enable near infrared fluorescence image-guided resection at short, medium and long tissue depths. Naphthalocyanine dyes have high quantum yields and may further act as chelators of radionuclides. Upon injection of the liquid marker, a gel-like depot is formed in situ at the site of injection, wherein the fluorescent dye and radionuclide is retained. The radiolabeled markers were optimized for minimal fluorescence quenching and high retention of the positron emission tomography radionuclide 64 Cu. The performance of the radiolabeled marker was tested in vivo in mice, where it displayed high photostability over a period of 4 weeks, and high retention of 64 Cu for 48 hours. The retention and biodistribution of 64 Cu was quantified via PET/CT, and the fluorescence emission by an in vivo imaging system. The presented data demonstrate proof-of-concept for naphthalocyanine markers as multimodal imaging agents that can bridge the precision of diagnostic imaging into surgical interventions.

Precisely translating computed tomography diagnosis accuracy into therapeutic intervention by a carbon-iodine conjugated polymer

“…A surgical marker that can bridge this gap by identifying occult lesions both under instrumental guidance and by direct visual observation is highly desirable in clinic 20,56 . In addition to the ultraefficient CT imaging characteristic, PIDA can preserve its unique deep blue color in vivo for over 1 week after the injection (Supplementary Fig.…”

Radio-Guided Lung Surgery: A Feasible Approach for a Cancer Precision Medicine

“…A biocompatible marker based on sucrose acetate isobutyrate, ethanol, and a multifunctional naphthalocyanine (NC) dye was developed by Wang et al [ 48 ]. This compound is characterized by near-infrared fluorescence which makes an image-guided resection possible at long tissue depths.…”