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Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.

ABSTRACT: Maximal surgical resection of glioma remains the single most effective treatment. Tools to guide the resection while avoiding removal of normal brain tissues can aid surgeons in achieving optimal results. One strategy to achieve this goal is to rely upon interoperative fluorescence staining of tumor cells in vivo, that can be visualized by the surgeon during resection. Towards this goal we have designed a biodegradable fluorescent mini nano imaging agent (NIA) with high specificity for U87MG glioma cells and previously unmet high light emission. The NIA is the conjugate of polymalic acid (PMLA) with chlorotoxin for tumor targeting, indocyanine green (ICG) for NIR fluorescence and the tri-leucin peptide as fluorescence enhancer. PMLA as a multivalent platform carries several molecules of ICG and the other ligands. The NIA recognizes multiple sites on glioma cell surface, demonstrated by the effects of single and combined competitors. Systemic IV injection into xenogeneic mouse model carrying human U87MG glioblastoma indicated vivid tumor cell binding and internalization of NIA resulting in intensive and long-lasting tumor fluorescence. The NIA is shown to greatly improve tumor removal supporting its utility in clinical applications.

SUBMITTER: Patil R

PROVIDER: S-EPMC6574176 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.

Patil Rameshwar R Galstyan Anna A Sun Tao T Shatalova Ekaterina S ES Butte Pramod P Mamelak Adam N AN Carico Christine C Kittle David S DS Grodzinski Zachary B ZB Chiechi Antonella A Ding Hui H Black Keith L KL Ljubimova Julia Y JY Holler Eggehard E

Biomaterials 20190323

Maximal surgical resection of glioma remains the single most effective treatment. Tools to guide the resection while avoiding removal of normal brain tissues can aid surgeons in achieving optimal results. One strategy to achieve this goal is to rely upon interoperative fluorescence staining of tumor cells in vivo, that can be visualized by the surgeon during resection. Towards this goal we have designed a biodegradable fluorescent mini nano imaging agent (NIA) with high specificity for U87MG gli ...[more]

PMID: 30933776

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Project description:BACKGROUND:After an esophagectomy, the stomach is most commonly used to restore continuity of the upper gastrointestinal tract. These esophago-gastric anastomoses are prone to serious complications such as leakage associated with high morbidity and mortality. Graft perfusion is considered to be an important predictor for anastomotic integrity. Based on the current literature we believe Indocyanine green fluorescence angiography (ICGA) is an easy assessment tool for gastric tube (GT) perfusion, and it might predict anastomotic leakage (AL). AIM:To evaluate feasibility and effectiveness of ICGA in GT perfusion assessment and as a predictor of AL. METHODS:This study was designed according to the PRISMA guidelines and registered in the PROSPERO database. PubMed and EMBASE were independently searched by 2 reviewers for studies presenting data on intraoperative ICGA GT perfusion assessment during esophago-gastric reconstruction after esophagectomy. Relevant outcomes such as feasibility, complications, intraoperative surgical changes based on ICGA findings, quantification attempts, anatomical data and the impact of ICGA on postoperative anastomotic complications, were collected by 2 independent researchers. The quality of the included articles was assessed based on the Methodological Index for Non-Randomized Studies. The 19 included studies presented data on 1192 esophagectomy patients, in 758 patients ICGA was used perioperative to guide esophageal reconstruction. RESULTS:The 19 included studies for qualitative analyses all described ICGA as a safe and easy method to evaluate gastric graft perfusion. AL occurred in 13.8% of the entire cohort, 10% in the ICG guided group and 20.6% in the control group (P < 0.001). When poorly perfused cases are excluded from the analyses, the difference in AL was even larger (AL well-perfused group 6.3% vs control group 20.5%, P < 0.001). The AL rate in the group with an altered surgical plan based on the ICG image was 6.5%, similar to the well perfused group (6.3%) and significantly less than the poorly perfused group (47.8%) (P < 0.001), suggesting that the technique is able to identify and alter a potential bad outcome. CONCLUSION:ICGA is a safe, feasible and promising method for perfusion assessment. The lower AL rate in the well perfused group suggest that a good fluorescent signal predicts a good outcome.

Dataset Information

Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.

Publications

Polymalic acid chlorotoxin nanoconjugate for near-infrared fluorescence guided resection of glioblastoma multiforme.

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