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Deuterated Indocyanine Green (ICG) with Extended Aqueous Storage Shelf-Life: Chemical and Clinical Implications.

ABSTRACT: Indocyanine Green (ICG) is a clinically approved near-infrared fluorescent dye that is used extensively for various imaging and diagnostic procedures. One drawback with ICG is its instability in water, which means that reconstituted clinical doses have to be used very shortly after preparation. Two deuterated versions of ICG were prepared with deuterium atoms on the heptamethine chain, and the spectral, physiochemical, and photostability properties were quantified. A notable mechanistic finding is that self-aggregation of ICG in water strongly favors dye degradation by a photochemical oxidative dimerization reaction that gives a nonfluorescent product. Storage stability studies showed that replacement of C-H with C-D decreased the dimerization rate constant by a factor of 3.1, and it is likely that many medical and preclinical procedures will benefit from the longer shelf-lives of these two deuterated ICG dyes. The discovery that ICG self-aggregation promotes photoinduced electron transfer can be exploited as a new paradigm for next-generation photodynamic therapies.

SUBMITTER: Li DH

PROVIDER: S-EPMC8530945 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Deuterated Indocyanine Green (ICG) with Extended Aqueous Storage Shelf-Life: Chemical and Clinical Implications.

Li Dong-Hao DH Smith Bradley D BD

Chemistry (Weinheim an der Bergstrasse, Germany) 20210924 58

Indocyanine Green (ICG) is a clinically approved near-infrared fluorescent dye that is used extensively for various imaging and diagnostic procedures. One drawback with ICG is its instability in water, which means that reconstituted clinical doses have to be used very shortly after preparation. Two deuterated versions of ICG were prepared with deuterium atoms on the heptamethine chain, and the spectral, physiochemical, and photostability properties were quantified. A notable mechanistic finding ...[more]

PMID: 34403531

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Project description:Background: Indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) has been recently adopted in pediatric minimally invasive surgery (MIS). This study aimed to report our experience with ICG-guided NIRF in pediatric laparoscopy and robotics and evaluate its usefulness and technique of application in different pediatric pathologies. Methods: ICG technology was adopted in 76 laparoscopic and/or robotic procedures accomplished in a single division of pediatric surgery over a 24-month period (January 2018-2020): 40 (37 laparoscopic, three robotic) left varicocelectomies with intra-operative lymphography; 13 (10 laparoscopic, three robotic) renal procedures: seven partial nephrectomies, three nephrectomies, and three renal cyst deroofings; 12 laparoscopic cholecystectomies; five robotic tumor excisions; three laparoscopic abdominal lymphoma excisions; three thoracoscopic procedures: two lobectomies and one lymph node biopsy for suspected lymphoma. The ICG solution was administered into a peripheral vein in all indications except for varicocele and lymphoma in which it was, respectively, injected into the testis body or the target organ. Regarding the timing of the administration, the ICG solution was administered intra-operatively in all indications except for cholecystectomy in which the ICG injection was performed 15-18 h before surgery. Results: No conversions to open or laparoscopy occurred. No adverse and allergic reactions to ICG or other postoperative complications were reported. Conclusions: Based upon our 2 year experience, we believe that ICG-guided NIRF is a very useful tool in pediatric MIS to perform a true imaged-guided surgery, allowing an easier identification of anatomic structures and an easier surgical performance in difficult cases. The most common applications in pediatric surgery include varicocele repair, difficult cholecystectomy, partial nephrectomy, lymphoma, and tumors excision but further indications will be soon discovered. ICG-enhanced fluorescence was technically easy to apply and safe for the patient reporting no adverse reactions to the product. The main limitation is represented by the specific equipment needed to apply ICG-guided NIRF in laparoscopic procedures, that is not available in all centers whereas the ICG system Firefly® is already integrated into the robotic platform.

Project description:BackgroundVideo-Assisted and Robotic-Assisted techniques become constantly more prominent practice in thoracic surgery for lung cancer. Furthermore, the increased frequency in detection of small lung cancers makes the intra-operative identification of these cancers even more challenging. Indocyanine Green (ICG) is one of the most commonly used dyes that assists surgeons identify small lung cancers intra-operatively. Our study aimed to evaluate the effectiveness and safety of ICG in lung cancer detection.MethodsWe performed a systematic review of the literature by screening the databases of MEDLINE, EMBASE, CENTRAL and Scopus until 30th April 2022 and the first 300 articles of Google Scholar for any suitable grey literature. We included any study that investigated the effectiveness of ICG in lung cancer detection. We excluded studies that explored the use of ICG only in identification of intersegmental planes, lymph node mapping, case reports and non-English articles. We aimed to perform a meta-analysis on test accuracy studies using hierarchical summary receiver operating characteristic (HSROC) and the bivariate random-effects models. In cases where the data for a localization technique was not sufficient for that analysis, it was presented with tables with narrative purposes. Each study was assessed for Risk of Bias (RoB) and Applicability using the QUADAS-2 tool.ResultsWe found 30 eligible studies that included a total of 1,776 patients who underwent ICG localization of pulmonary nodules. We identified three ICG localization techniques: CT-guided, endobronchial and intravenous. From the 30 studies, 13 investigated CT-guided localization, 12 explored an endobronchial method while 8 studies administered ICG intravenously the median reported success rate was 94.3% (IQR: 91.4%-100%) and 98.3% (IQR: 94%-100%) for the first two techniques respectively. Intravenous ICG lung cancer localization showed Sensitivity of 88% (95% CI: 59%-0.97%) and Specificity of 25% (95% CI: 0.04%-0.74%). There were 15.2% (150/989) patients who experienced complications from CT guided ICG localization. No ICG-related complications were reported in endobronchial or intravenous techniques.ConclusionOur study provides a comprehensive review of the literature on ICG localization techniques for lung cancer. Current evidence suggests that ICG is boh effective and safe. Further prospective research with standardized protocols across multiple thoracic units is required in order to accurately validate these findings.

Project description:BackgroundRecently, we reported the feasibility of indocyanine green (ICG) near-infrared fluorescence (NIRF) imaging to identify extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC) in pediatric patients. This paper aimed to describe the use of a new technology, RUBINA™, to perform intra-operative ICG fluorescent cholangiography (FC) in pediatric LC.MethodsDuring the last year, ICG-FC was performed during LC using the new technology RUBINA™ in two pediatric surgery units. The ICG dosage was 0.35 mg/Kg and the median timing of administration was 15.6 h prior to surgery. Patient baseline, intra-operative details, rate of biliary anatomy identification, utilization ease, and surgical outcomes were assessed.ResultsThirteen patients (11 girls), with median age at surgery of 12.9 years, underwent LC using the new RUBINA™ technology. Six patients (46.1%) had associated comorbidities and five (38.5%) were practicing drug therapy. Pre-operative workup included ultrasound (n = 13) and cholangio-MRI (n = 5), excluding biliary and/or vascular anatomical anomalies. One patient needed conversion to open surgery and was excluded from the study. The median operative time was 96.9 min (range 55-180). Technical failure of intra-operative ICG-NIRF visualization occurred in 2/12 patients (16.7%). In the other cases, ICG-NIRF allowed to identify biliary/vascular anatomic anomalies in 4/12 (33.3%), including Moynihan's hump of the right hepatic artery (n = 1), supravescicular bile duct (n = 1), and short cystic duct (n = 2). No allergic or adverse reactions to ICG, post-operative complications, or reoperations were reported.ConclusionOur preliminary experience suggested that the new RUBINA™ technology was very effective to perform ICG-FC during LC in pediatric patients. The advantages of this technology include the possibility to overlay the ICG-NIRF data onto the standard white light image and provide surgeons a constant fluorescence imaging of the target anatomy to assess position of critical biliary structures or presence of anatomical anomalies and safely perform the operation.

Dataset Information

Deuterated Indocyanine Green (ICG) with Extended Aqueous Storage Shelf-Life: Chemical and Clinical Implications.

Publications

Deuterated Indocyanine Green (ICG) with Extended Aqueous Storage Shelf-Life: Chemical and Clinical Implications.

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