Abstract

Surgical resection of cancer remains an important treatment modality. Despite advances in preoperative imaging, surgery itself is primarily guided by the surgeon’s ability to locate pathology with conventional white light imaging. Fluorescence-guided surgery (FGS) can be used to define tumor location and margins during the procedure. Intraoperative visualization of tumors may not only allow more complete resections but also improve safety by avoiding unnecessary damage to normal tissue which can also reduce operative time and decrease the need for second-look surgeries. A number of new FGS imaging probes have recently been developed, complementing a small but useful number of existing probes. In this review, we describe current and new fluorescent probes that may assist FGS.

Highlights

  • Surgery is a primary mode of treatment for many malignancies

  • We focus on the currently used Food and Drug Administration (FDA)-approved fluorescent probes and new types of fluorescence imaging probes for Fluorescence-guided surgery (FGS) that are under development

  • 5-aminolevulinic acid (ALA) is the major substrate for protoporphyrin synthesis, and has been used clinically for tumor detection and tumor treatment, as a FDA-approved substance. 5-Aminolevulinic acid (5-ALA), typically administered in a topical or oral form, induces synthesis and accumulation of the fluorescent molecule protoporphyrin IX (PpIX) in epithelia and neoplastic tissues [83, 85, 86]. 5-ALA-induced PpIX exhibits multiple physiochemical states depending on the microenvironment

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Summary

INTRODUCTION

Surgery is a primary mode of treatment for many malignancies. For example, 63–98% of patients with lung, breast, bladder, and colorectal cancer will undergo surgery [1]. The ability to resect tumor currently relies on the visual localization of the tumor and/or the ability to palpate it The former is limited by the low contrast between tumors and background tissue and many small tumors may be missed. Many studies show that positive margins, defined as the identification of tumor cells at the cut edge of a surgical specimen, are associated with increased local recurrence and indicate a poor prognosis in most cancer types including head and neck cancers [2], breast cancer [3, 4], non-small-cell lung cancer [5], colorectal cancer [6], bladder cancer [7], and prostate cancer [8]. Intraoperative systems are costly, complex and require space Their use interrupts the normal workflow of the surgical procedure lengthening operative/anesthesia times. Practical methods for augmenting the surgeon’s ability to resect tumors are needed One such method is fluorescence-guided surgery (FGS). We focus on the currently used Food and Drug Administration (FDA)-approved fluorescent probes and new types of fluorescence imaging probes for FGS that are under development

CURRENT FGS
Hepatocellular carcinoma Liver metastases Breast cancer
Cholecystectomy Esophagectomy Gastrectomy Adrenalectomy Brain aneurysm
CLINICALLY AVAILABLE FLUORESCENCE IMAGING
CURRENT CLINICAL USE OF FLUORESCENCE IMAGING PROBES
Laser LED Laser Laser Laser
Indocyanin green MB Porphyrin
Fluorescein Sodium
NEW FLUORESCENCE IMAGING PROBES
Activatable Fluorescent Probes
Sprayable Activatable Fluorescent Probes
Findings
SUMMARY
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