Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents

Abstract

Cancer surgery remains the primary treatment option for most solid tumors and can be curative if all malignant cells are removed. Surgeons have historically relied on visual and tactile cues to maximize tumor resection, but clinical data suggest that relapse occurs partially due to incomplete cancer removal. As a result, the introduction of technologies that enhance the ability to visualize tumors in the operating room represents a pressing need. Such technologies have the potential to revolutionize the surgical standard-of-care by enabling real-time detection of surgical margins, subclinical residual disease, lymph node metastases and synchronous/metachronous tumors. Fluorescence-guided surgery (FGS) in the near-infrared (NIRF) spectrum has shown tremendous promise as an intraoperative imaging modality. An increasing number of clinical studies have demonstrated that tumor-selective FGS agents can improve the predictive value of fluorescence over non-targeted dyes. Whereas NIRF-labeled macromolecules (i.e., antibodies) spearheaded the widespread clinical translation of tumor-selective FGS drugs, peptides and small-molecules are emerging as valuable alternatives. Here, we first review the state-of-the-art of promising low molecular weight agents that are in clinical development for FGS; we then discuss the significance, application and constraints of emerging tumor-selective FGS technologies.

Biodistributions and Imaging of Poly(ethylene glycol)-Conjugated Silicon Quantum Dot Nanoparticles in Osteosarcoma Models via Intravenous and Intratumoral Injections

“…The TEM images also confirm that the BSA-coated SiQDNPs have particle sizes around 100 nm and are composed of multiple SiQDs (Figure G,H). After the BSA coating, 4-arm PEG-NH 2 molecules can be conjugated to the BSA-coated SiQDNPs via amide bond formation, and then the rest of the available amine groups can be reacted with NHS-PEG–OH to extend the overall PEG conjugation (Figure C) or with NHS-PEG-folic acid (FA) to enhance the targeting efficiency to the osteosarcoma (Figure D) . The conjugation of PEG to the SiQDNPs is confirmed by the larger hydrodynamic diameter in pH 7 0.1 M PB (174 nm, blue line in Figure I), compared to the BSA-coated SiQDNPs.…”

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

“…Several low-molecular-weight FGS agents have advanced to clinical trials, − and the folate receptor-targeted agent OTL-38 recently gained regulatory approval for intraoperative identification of ovarian cancer. Given the similar need for intraoperative guidance during GEP-NET surgery, we systematically examined the translational utility of MMC­(FNIR-Tag)-TOC in the present study.…”

Translocator Protein 18 kDa (TSPO): A Promising Molecular Target for Image-Guided Surgery of Solid Cancers

“… 29 , 30 At present, several FIGS agents based on macromolecules (antibodies), peptides, and small molecules have been developed, and some of the candidates have progressed to clinical trials. These agents were designed to target several molecular biomarkers, such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), 31 gastrin-releasing peptide receptor (GRPR), 32 somatostatin receptor 5 (SSTR5), 33 and the cluster of differentiation 24 (CD-24). 34 …”