Evaluation of Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided Surgery of Cancer

Because
the most reliable therapy for cancer involves quantitative resection
of all diseased tissue, considerable effort has been devoted to improving
a surgeon’s ability to locate and remove all malignant lesions.
With the aid of improved optical imaging equipment, we and others
have focused on developing tumor-targeted fluorescent dyes to selectively
illuminate cancer nodules during surgery. We describe here the design,
synthesis, optical properties, in vitro and in vivo tumor specificity/affinity,
pharmacokinetics, preclinical toxicology, and some clinical application
of a folate receptor (FR)-targeted NIR dye (OTL38) that concentrates
specifically in cancer tissues and clears rapidly from healthy tissues.
We demonstrate that OTL38 binds FR-expressing cells with ∼1
nM affinity and eliminates from receptor negative tissues with a half-time
of <30 min. We further show that OTL38 enables visualization of
malignant lesions at concentrations less than 100-fold those required
to elicit signs of toxicity. Since OTL38 also provides excellent tumor
contrast in both murine tumor models and human cancer patients, we
conclude that OTL38 constitutes an excellent NIR dye for fluorescence-guided
resection of malignant lesions in cancer patients.