Beyond the margins: real-time detection of cancer using targeted fluorophores

Abstract

Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging. Rapid developments in fluorophores with improved characteristics, detection instrumentation, and targeting strategies led to the clinical testing in the early 2010s of the first targeted NIR fluorophores for intraoperative cancer detection. The foundations for the advances that underline this technology continue to be nurtured by the multidisciplinary collaboration of chemists, biologists, engineers, and clinicians. In this Review, we highlight the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, and consider the unique challenges associated with their effective application in clinical settings.

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

“…The intraoperative detection of an imaging agent depends on various biological and optical factors ( Table 1). The considerable increase in the number of clinical trials in the FI field has led to the development of a variety of FI systems [8]. However, as the imaging system represents the last link in the chain, sensitivity (i.e., detection limit) of the imaging system is crucial [9].…”

Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages

“…The idea of performing NIR-imaging with CA IX-oligomer will provide several advantages including its use as (i) agent for tumor image guided RCC surgery in the clinic, as well as (ii) meaningful insights into the therapeutic outcome and safety of nanoformulation in RCC model. It is well known that clinically small molecule NIR imaging agents have excellent ability to distinguish the tumor lesion from healthy tissue in imaging-guided surgery as noted in NCT02317705 and NCT01778933 [72]. The results show CA IX-S0456 selectively home to the orthotopic subcutaneous Evr-res A498 tumor as compared to control (Figure 7 A and C).…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…[115][116][117][118][119][120] Moreover, OTL38, an NIRF agent binding with folate receptor-α has entered Phase III clinical trial stage for patients with ovarian cancer [121] and Phase II clinical trial stage for patients with pulmonary adenocarcinomas. Rosenthal and co-workers devoted a considerable amount of efforts in researching tumor-specific fluorescent probes by conjugating antibodies (e.g., panitumumab, cetuximab, etc.)…”

“…Rosenthal and co-workers devoted a considerable amount of efforts in researching tumor-specific fluorescent probes by conjugating antibodies (e.g., panitumumab, cetuximab, etc.) [115] These exciting advances also have inspired the further development of NIR-II fluorophores and nanoprobes ( Table 2) to improve limited penetration and tumor retention of NIRF imaging, as well as the development of appropriate instruments for FGS. [115][116][117][118][119][120] Moreover, OTL38, an NIRF agent binding with folate receptor-α has entered Phase III clinical trial stage for patients with ovarian cancer [121] and Phase II clinical trial stage for patients with pulmonary adenocarcinomas.…”