Tailored Near-Infrared Contrast Agents for Image Guided Surgery

Abstract

The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge.

Revisiting the classification of NIR-absorbing/emitting nanomaterials for in vivo bioapplications

“…Alternatively, for angiography or tissue labeling in living organisms, a different approach is to develop NIR dye molecule assays in the NIR spectral region (700-900 nm) to reduce the autofluorescent background and assist image-guided surgery. 110 Several IRDye and CyDye families have been synthesized. Cy5.5 has strong emission at 690 nm upon excitation at 670 nm.…”

“…112 In addition to exhibiting increased stability in serum, modified ICG molecules have satisfactory in vivo biodistribution and clearance. 110 In general, the quantum yield of single-photon excited IR fluorophores must be 40.01. 113 This result is much higher than the multiphoton process for IR fluorophore, which is o10 − 8 .…”

Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates

“…11,[18][19][20] Such properties likely arise from the reported rapid urinary clearance of these zwitterionic molecules or their metabolites. 11,21 In this study, we compare the in vitro and in vivo optical imaging characteristics of mAb-FNIR-774 and mAb-FNIR-Z-759 conjugates.…”

Sensing the Whole Body and Clinical Diagnostics

“…It is non-toxic, still its quantum yield is rather small. Among new developments are the zwitterionic heptamethine dyes that possess advanced spectroscopic properties, demonstrate high solubility and rapid renal clearance (Njiojob et al 2015 ). Their covalent modifi cation is possible via appended amino or carboxylic groups.…”

“…The surgeon's display can be one of several form factors, including a standard computer monitor, goggles or a wall projector. Current imaging systems operate at a suffi cient (Njiojob et al 2015 ) ( c ) The imaging system for surgical operation that allows obtaining near-IR image and its projection on computer screen (Gioux et al 2010 ). ( d ) Hand-held spectroscopic device for intraoperative tumor detection in vivo (Mohs et al 2010 ).…”