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Fluorescence-guided hepatobiliary surgery with long and short wavelength fluorophores.

ABSTRACT: Importance:Fluorescence-guided surgery (FGS) is a potentially powerful tool for hepatobiliary (HPB) surgery. The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited. Objective:The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue (MB), 5-aminolevulinic acid (5-ALA), and indocyanine green (ICG) for clinical intra-operative image-guidance during HPB surgery. Evidence Review:Approaches such as dosing, timing, imaging devices and comparative endpoints are summarized. The feasibility and safety of fluorophores in visualizing the biliary tree, identify biliary leaks, outline anatomic hepatic segments, identify tumors, and evaluate perfusion and graft function in liver transplants are discussed. Findings:Tumor-specific probes are a promising advancement in FGS with a greater degree of specificity. The current status of tumor-specific probes being evaluated in clinical trials are summarized. Conclusions and Relevance for Reviews:Relevant discussion of promising tumor-specific probes in pre-clinical development are discussed. Fluorescence-guidance in HPB surgery is relatively new, but current literature shows that the dyes are reliably able to outline desired structures with a variety of dosing, timing, and imaging devices to provide real-time intra-operative anatomic information to surgeons. Development of tumor-specific probes will further advance the field of HPB surgery especially during oncologic resections.

SUBMITTER: Lwin TM

PROVIDER: S-EPMC7603922 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Fluorescence-guided hepatobiliary surgery with long and short wavelength fluorophores.

Lwin Thinzar M TM Hoffman Robert M RM Bouvet Michael M

Hepatobiliary surgery and nutrition 20201001 5

<h4>Importance</h4>Fluorescence-guided surgery (FGS) is a potentially powerful tool for hepatobiliary (HPB) surgery. The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited.<h4>Objective</h4>The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue (MB), 5-aminolevulinic acid (5-ALA), and indocyanine green (ICG) for clinical intra-operative image-guidance during HPB surgery.<h4>Evide ...[more]

PMID: 33163512

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Project description:The use of NIR-fluorescence imaging to demarcate tumour boundaries for real-time guidance of their surgical resection has a huge untapped potential. However, fluorescence imaging using molecular fluorophores, even with a targeting biomolecule attached, has a major shortcoming of signal interference from non-specific background fluorescence outside the region of interest. This poor selectivity necessitates prolonged time delays to allow clearance of background fluorophore and retention within the tumour prior to image acquisition. In this report, an innovative approach to overcome this issue is described in which cancer targeted off to on bio-responsive NIR-fluorophores are utilised to switch-on first within the tumour. Bio-responsive cRGD, iRGD and PEG conjugates have been synthesised using activated ester/amine or maleimide/thiol couplings to link targeting and fluorophore components. Their off to on emission responses were measured and compared with an always-on non-responsive control with each bio-responsive derivative showing large fluorescence enhancement values. Live cell imaging experiments using metastatic breast cancer cells confirmed in vitro bio-responsive capabilities. An in vivo assessment of MDA-MB 231 tumour imaging performance for bio-responsive and always-on fluorophores was conducted with monitoring of fluorescence distributions over 96 h. As anticipated, the always-on fluorophore gave an immediate, non-specific and very strong emission throughout whereas the bio-responsive derivatives initially displayed very low fluorescence. All three bio-responsive derivatives switched on within tumours at time points consistent with their conjugated targeting groups. cRGD and iRGD conjugates both had effective tumour turn-on in the first hour, though the cRGD derivative had superior specificity for tumour over the iRGD conjugate. The pegylated derivative had similar switch-on characteristics but over a much longer period, taking 9 h before a significant emission was observable from the tumour. Evidence for in vivo active tumour targeting was obtained for the best performing cRGD bio-responsive NIR-AZA derivative from competitive binding studies. Overall, this cRGD-conjugate has the potential to overcome the inherent drawback of targeted always-on fluorophores requiring prolonged clearance times and shows excellent potential for clinical translation for intraoperative use in fluorescence guided tumour resections.

Dataset Information

Fluorescence-guided hepatobiliary surgery with long and short wavelength fluorophores.

Publications

Fluorescence-guided hepatobiliary surgery with long and short wavelength fluorophores.

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