Whole-body fluorescence cryotomography identifies a fast-acting, high-contrast, durable contrast agent for fluorescence-guided surgery.

in Theranostics by Augustino V Scorzo, Brook K Byrd, Caleb Y Kwon, Rendall R Strawbridge, Kimberley S Samkoe, P Jack Hoopes, Keith D Paulsen, David W Roberts, Scott C Davis

TLDR

  • The study is trying to find a fluorescent agent that can help doctors see brain tumors better during surgery. The study uses a special camera to take pictures of the fluorescent agent in the brain and compares it to the pictures taken with a regular MRI machine. The study found that one agent, TMR-PEG1k, works really well and is a good candidate for helping doctors see brain tumors during surgery.

Abstract

Imaging of tumor-specific fluorescent contrast agents to guide tumor removal has been shown to improve outcomes and is now standard practice for some neurosurgical procedures. However, many agents require administration hours before surgery, a practical challenge, and may exhibit inconsistent concordance with contrast-enhanced MRI (CE-MRI), the current standard for diagnosing and guiding glioma removal. A fluorescent agent that accurately marks tumor shortly after administration and is otherwise similar to CE-MRI would help overcome these shortcomings.We used whole-body 3-D fluorescence cryo-imaging and co-registered CE-MRI volumes to evaluate several fluorescent contrast agent candidates for diagnostic performance and concordance with CE-MRI. Mice with brain tumors were administered a cocktail of fluorescent agent candidates and a MRI contrast agent, and then imaged with MRI and fluorescence cryo-imaging at several timepoints after administration. The high-resolution 3-D cryo-imaging volumes of the fluorescent agents were used to determine diagnostic performance metrics and correlation with CE-MRI.While all agents showed positive metrics, one agent, tetramethylrhodamine conjugated to a small polyethylene glycol chain (TMR-PEG1k), outperformed the others, exhibiting minimal normal brain signal, high tumor-to-background-ratio, diagnostic accuracy, and cross-correlation to CE-MRI at all post-administration timepoints (10-90 min) and tumor lines examined.These favorable properties establish TMR-PEG1k as a promising candidate for surgical guidance.

Overview

  • The study aims to evaluate several fluorescent contrast agent candidates for their diagnostic performance and concordance with contrast-enhanced MRI (CE-MRI) in mice with brain tumors. The study uses whole-body 3-D fluorescence cryo-imaging and co-registered CE-MRI volumes to evaluate the agents. The study uses a cocktail of fluorescent agent candidates and a MRI contrast agent, and the fluorescence cryo-imaging volumes are used to determine diagnostic performance metrics and correlation with CE-MRI. The primary objective of the study is to identify a fluorescent agent that accurately marks tumor shortly after administration and is otherwise similar to CE-MRI.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies one agent, tetramethylrhodamine conjugated to a small polyethylene glycol chain (TMR-PEG1k), that outperforms the others in terms of minimal normal brain signal, high tumor-to-background-ratio, diagnostic accuracy, and cross-correlation to CE-MRI at all post-administration timepoints and tumor lines examined. The study suggests that TMR-PEG1k is a promising candidate for surgical guidance.

Implications and Future Directions

  • The study's findings suggest that TMR-PEG1k is a promising candidate for surgical guidance. The study identifies several limitations, including the need for further preclinical studies to evaluate the safety and efficacy of TMR-PEG1k in humans. The study suggests several future research directions, including the development of a human-specific fluorescent agent, the evaluation of TMR-PEG1k in a larger animal model, and the exploration of the use of TMR-PEG1k in combination with other imaging modalities.
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