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Published on: November 19, 2019
Rapid and Selective Targeting of Heterogeneous Pancreatic Neuroendocrine Tumors
G Kate Park1, Jeong Heon Lee1, Eduardo Soriano2
1Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Abstract:
Design of tissue-specific contrast agents to delineate tumors from background tissues is a major unmet clinical need for ultimate surgical interventions. Bioconjugation of fluorophore(s) to a ligand has been mainly used to target overexpressed receptors on tumors. However, the size of the final targeted ligand can be large, >20 kDa, and cannot readily cross the microvasculature to meet the specific tissue, resulting in low targetability with a high background. Here, we report a small and hydrophilic phenoxazine with high targetability and retention to pancreatic neuroendocrine tumor. This bioengineered fluorophore permits sensitive detection of ultrasmall (<0.5 mm) ectopic tumors within a few seconds after a single bolus injection, highlighting every tumor in the pancreas from the surrounding healthy tissues with reasonable half-life. The knowledge-based approach and validation used to develop structure-inherent tumor-targeted fluorophores have a tremendous potential to improve treatment outcome by providing definite tumor margins for image-guided surgery.
Insights
Researchers developed a small, hydrophilic phenoxazine fluorophore for precise pancreatic neuroendocrine tumor detection. This novel contrast agent enables rapid, sensitive visualization of small tumors, improving surgical guidance.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Oncology
Background:
- Accurate tumor delineation is critical for surgical success, yet current contrast agents face limitations.
- Existing tumor-targeting ligands, often large bioconjugates (>20 kDa), exhibit poor microvasculature penetration, leading to suboptimal targetability and high background signal.
- There is a significant unmet clinical need for small, efficient contrast agents for precise tumor margin identification.
Purpose of the Study:
- To design and develop a novel, small, and hydrophilic phenoxazine-based fluorophore.
- To achieve high targetability and retention in pancreatic neuroendocrine tumors (PNETs).
- To enable sensitive and rapid detection of even ultrasmall ectopic tumors for improved image-guided surgery.
Main Methods:
- A knowledge-based approach was employed to engineer a structure-inherent, tumor-targeted fluorophore.
- The developed phenoxazine derivative was evaluated for its targeting efficiency and retention in PNET models.
- In vivo studies assessed the fluorophore's capability for sensitive detection of small tumors following a single bolus injection.
Main Results:
- A small, hydrophilic phenoxazine fluorophore demonstrated high targetability and retention for pancreatic neuroendocrine tumors.
- The bioengineered fluorophore enabled sensitive detection of ultrasmall (<0.5 mm) ectopic tumors within seconds.
- The agent effectively highlighted all pancreatic tumors against surrounding healthy tissues with a reasonable half-life.
Conclusions:
- The novel phenoxazine fluorophore offers a significant advancement in contrast agent design for PNETs.
- This approach provides a potential solution for accurate tumor margin definition in image-guided surgery.
- The knowledge-based design strategy holds promise for developing other targeted imaging agents for improved treatment outcomes.
