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Selective Colorectal Cancer Imaging by use of Indocyanine Green versus Next-generation Cancer-Specific Targeting Agents

Haseeb Kothar, Ronan Cahill. Mater Misericordiae University Hospital

 

Current clinical advances in operative near-infrared visualisation of cells, tissues and structures are predicated on the use of commercial available near-infrared cameras to excite and visualise emission energy from non-selective, approved compounds (predominantly indocyanine green (ICG)). It is expected that new generation compounds wholly selective for specific cellular components are now needed for further advance and a variety of molecular targets have been proposed and are being developed primarily for oncological imaging purposes. Recent publications have however suggested ICG itself is retained within malignant tissue differently to its uptake and clearance from surrounding non-malignant tissue which is important for two reasons. Firstly, it exploits and makes visual the increased vascular permeability and disordered clearance associated with carcinogenesis which is a common endpoint of a variety of mediators including but not limited to VEGF. This raises the useful option of targeting downstream effects of cancer compounds on a metabolic basis as opposed to tagging individual cell or antigen components. This means that a single agent could be used to target a variety of cancers rather then needing a specific one for each specific sub-type as well as obviating the issue of  cancer cells heterogeneity even in a single cancer deposit. Second, it is very likely that some or all of the “localisation” effect of proposed selective compounds may well be due to a similar phenomenum rather then cell-specific binding and may make distinction from other areas of similar metabolic behaviour (ie inflammatory regions) difficult. The crucial step-advance for such agent development so may well relate to timing of compound delivery and “visualisation window” at the region of interest rather then highly selective oncocellular-targeting. To illustrate this in more detail, we have been examining the tissue-specific effects and actions of near-infrared excitation in patients (n=7) with localised malignant colorectal primaries receiving an aliquot of ICG before such examination at the time of resection. ICG can be selectively apparent in the colorectal primary 15 minutes after its systemic administration likely due to altered vascular dynamics. Additional dose-related work has shown that early administration (40-180 minutes before examination) does not give useful information related to tumour fluorescence. Interestingly none of these patients had fluorescence seen within their regional lymphatics but none also had malignant lymph nodes associated with their large primaries on pathological examination. 


Presented at the SAGES 2017 Annual Meeting in Houston, TX.

Abstract ID: 88179

Program Number: P218

Presentation Session: iPoster Session (Non CME)

Presentation Type: Poster

33

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