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Updated: Dec 10, 2025
Optical Clearing and Imaging of Immunolabeled Kidney Tissue
Published on: July 22, 2019
Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport
Bujie Du1, Yue Chong1, Xingya Jiang1
1Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX, 75080, USA.
Abstract:
Renal tubular secretion is an active efflux pathway for the kidneys to remove molecules but has yet to be used to enhance kidney cancer targeting. We report indocyanine green (ICG) conjugated with a 2100 Da PEG molecule (ICG-PEG45) as a renal-tubule-secreted near-infrared-emitting fluorophore for hyperfluorescence imaging of kidney cancers, which cannot be achieved with hepatobiliary- and glomerular-clearable ICG. This pathway-dependent targeting of kidney cancer arises from the fact that the secretion pathway enables ICG-PEG45 to be effectively effluxed out of normal proximal tubules through P-glycoprotein transporter while being retained in cancerous kidney tissues with low P-glycoprotein expression. Tuning elimination pathways and utilizing different efflux kinetics of medical agents in normal and diseased tissues could be a new strategy for tackling challenges in disease diagnosis and treatments that cannot be addressed with passive and ligand-receptor-mediated active targeting.
Insights
Researchers developed a novel near-infrared fluorophore, indocyanine green conjugated with PEG (ICG-PEG45), for enhanced kidney cancer imaging. This targeted approach leverages renal tubular secretion for improved tumor visualization compared to traditional methods.
Area of Science:
- Biomedical Engineering
- Medical Imaging
- Oncology
Background:
- Renal tubular secretion is an active kidney efflux pathway not previously utilized for kidney cancer targeting.
- Current imaging agents often lack specificity for kidney cancers, necessitating improved diagnostic tools.
- Indocyanine green (ICG) clearance pathways (hepatobiliary and glomerular) limit its efficacy in kidney cancer detection.
Purpose of the Study:
- To develop a novel near-infrared (NIR) fluorophore for enhanced kidney cancer hyperfluorescence imaging.
- To utilize the renal tubular secretion pathway for targeted delivery and retention in kidney tumors.
- To investigate the role of P-glycoprotein transporter expression in differential retention of the fluorophore in normal versus cancerous kidney tissues.
Main Methods:
- Synthesis of indocyanine green conjugated with a 2100 Da PEG molecule (ICG-PEG45).
- Evaluation of ICG-PEG45 as a renal-tubule-secreted NIR-emitting fluorophore.
- Assessment of ICG-PEG45 retention in cancerous kidney tissues versus normal proximal tubules, considering P-glycoprotein transporter activity.
Main Results:
- ICG-PEG45 demonstrated effective renal tubular secretion and NIR emission for hyperfluorescence imaging of kidney cancers.
- The fluorophore was efficiently effluxed from normal proximal tubules via P-glycoprotein but retained in kidney cancers with low P-glycoprotein expression.
- This differential retention enabled pathway-dependent targeting and visualization of kidney cancers.
Conclusions:
- ICG-PEG45 represents a novel strategy for kidney cancer hyperfluorescence imaging by exploiting renal tubular secretion.
- Tuning elimination pathways based on differential transporter kinetics offers a new approach for disease diagnosis and treatment.
- This method overcomes limitations of passive and ligand-receptor-mediated targeting in challenging disease contexts.
