Indocyanine Green Fluorescence Imaging-Guided Surgery in Primary and Metastatic Liver Tumors

Lieto, Eva; Galizia, Gennaro; Cardella, Francesca; Mabilia, Andrea; Basile, Nicoletta; Castellano, Paolo; Orditura, Michele; Auricchio, A

doi:10.1177/1553350617751451

Cited by 41 publications

(32 citation statements)

References 42 publications

(69 reference statements)

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“…Much of the cutting-edge research in FGS focuses on imaging-targeted or environment-sensitive agents; 2,6,12,16,18 however, there is still substantial interest and research in nonspecific agents that exploit the vascular abnormalities found in most tumors, such as NaFl and indocyanine green. 13,22 These agents often already have a clinical foothold in other indications, have a safety record, and are envisioned as stand-alone or complementary tools for FGS. Combining these nonspecific agents with targeted agents with dual-agent compartment modeling can also help account for the effects of delivery and reveal more accurate information about the molecular targets.…”

Section: Discussionmentioning

confidence: 99%

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

Folaron¹,

Strawbridge²,

Samkoe

et al. 2019

Journal of Neurosurgery

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OBJECTIVE The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents. METHODS Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts. RESULTS Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%. CONCLUSIONS Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

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Section: Discussionmentioning

confidence: 99%

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

Folaron¹,

Strawbridge²,

Samkoe

et al. 2019

Journal of Neurosurgery

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“…In another study, Zanganeh et al administered ICG-conjugated nanotubes that significantly improved the observation of an accurate tumor site and confirmed the light absorption of cancer areas at the PAI level, in the meantime, the enhanced, robust system was also confirmed by the captured fluorescent images [ 154 ]. Furthermore, Lieto et al verified the validity of liver tumor surgery with the effective ICG-FI tool, which efficiently detected certain lesions and recognized other small tumors [ 155 ].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Leveraging Engineering of Indocyanine Green-Encapsulated Polymeric Nanocomposites for Biomedical Applications

et al. 2018

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In recent times, photo-induced therapeutics have attracted enormous interest from researchers due to such attractive properties as preferential localization, excellent tissue penetration, high therapeutic efficacy, and minimal invasiveness, among others. Numerous photosensitizers have been considered in combination with light to realize significant progress in therapeutics. Along this line, indocyanine green (ICG), a Food and Drug Administration (FDA)-approved near-infrared (NIR, >750 nm) fluorescent dye, has been utilized in various biomedical applications such as drug delivery, imaging, and diagnosis, due to its attractive physicochemical properties, high sensitivity, and better imaging view field. However, ICG still suffers from certain limitations for its utilization as a molecular imaging probe in vivo, such as concentration-dependent aggregation, poor in vitro aqueous stability and photodegradation due to various physicochemical attributes. To overcome these limitations, much research has been dedicated to engineering numerous multifunctional polymeric composites for potential biomedical applications. In this review, we aim to discuss ICG-encapsulated polymeric nanoconstructs, which are of particular interest in various biomedical applications. First, we emphasize some attractive properties of ICG (including physicochemical characteristics, optical properties, metabolic features, and other aspects) and some of its current limitations. Next, we aim to provide a comprehensive overview highlighting recent reports on various polymeric nanoparticles that carry ICG for light-induced therapeutics with a set of examples. Finally, we summarize with perspectives highlighting the significant outcome, and current challenges of these nanocomposites.

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“…Some clinical centers have reported the use of ICG molecular fluorescence imaging technology for the diagnosis and treatment of liver tumors [3][4][5][6]29]. However, whether it can improve the surgical treatment of liver tumors is still lack of domestic and foreign high-quality evidence.…”

Section: Discussionmentioning

confidence: 99%

Precise right hemihepatectomy for the treatment of hepatocellular carcinoma guided by fusion ICG fluorescence imaging

Yao¹,

Zhang²,

Ma³

et al. 2020

J. Cancer

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To evaluate the clinical significance of fusion indocyanine green (ICG) fluorescence imaging in precise right hemihepatectomy for the treatment of hepatocellular carcinoma (HCC). 47 patients with HCC who underwent right hemihepatectomy were retrospectively analyzed. 18 of them guided by fusion ICG fluorescence imaging (FIGFI) while 29 patients underwent conventional right hepatectomy without guidance. Compared to the patients with conventional treatment, the intraoperative blood loss of the patients with guided surgery was significantly less, and no transfusion and hepatic occlusion were performed during the operation. Liver function recovery faster in guided group. The incidence of postoperative complications is also lower, and the recurrence rate in one year is significantly reduced. ICG fluorescence range of 18 patients in liver surface was consistent with the ischemic line, and their postoperative liver cross-sections were clearly demarcation. There were no significant differences in the mean operation time, blood loss, postoperative hospital stays, cases of blood transfusion, complication rate, or postoperative peak volume of ALT and TB between positive or negative staining groups. Pathology results of all patients demonstrated HCC and negative margins, and microvascular invasion occurred in 8 cases. The average follow-up time of 18 patients was 16.7 months, and recurrence was found in 5 cases after surgery. FIGFI could guide the anatomical right hepatectomy with real-time increased radical rate, accuracy and safety for the treatment of HCC, and therefore showed a promising prospect.

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Indocyanine Green Fluorescence Imaging-Guided Surgery in Primary and Metastatic Liver Tumors

Abstract: ICG-FI-guided surgery was shown to be an effective tool to improve both intraoperative staging and radicality in the surgical treatment of primary and metastatic liver tumors.

Cited by 41 publications

References 42 publications

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

Leveraging Engineering of Indocyanine Green-Encapsulated Polymeric Nanocomposites for Biomedical Applications

Precise right hemihepatectomy for the treatment of hepatocellular carcinoma guided by fusion ICG fluorescence imaging

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