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Updated: Feb 12, 2026

Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
Published on: February 18, 2016
Folate Receptor Near-Infrared Optical Imaging Provides Sensitive and Specific Intraoperative Visualization of
Steve S Cho1,2, Ryan Zeh1, John T Pierce1
1Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Background:
Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα).
Objective:
To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging.
Methods:
Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm.
Results:
Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients.
Conclusion:
Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.
Insights
Near-infrared (NIR) imaging targeting folate receptor alpha (FRα) shows promise for detecting nonfunctional (NF) pituitary adenomas. This technique offers 100% sensitivity and specificity, potentially improving surgical resection rates.
Area of Science:
- Neurosurgery
- Medical Imaging
- Oncology
Background:
- Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but achieving complete removal can be challenging.
- NF adenomas characteristically overexpress folate receptor alpha (FRα).
Purpose of the Study:
- To evaluate the efficacy of targeting FRα for highly sensitive and specific intraoperative detection of NF pituitary adenomas using near-infrared (NIR) imaging.
Main Methods:
- Fourteen patients with NF pituitary adenoma received a preoperative infusion of the folate analog NIR dye OTL38.
- Intraoperative NIR fluorescence signal-to-background ratio (SBR) was measured during tumor resection.
- Immunohistochemistry assessed FRα expression, and postoperative MRI evaluated residual tumor.
Main Results:
- Nine FRα-overexpressing adenomas showed significantly higher NIR SBR (3.2 ± 0.52) compared to non-overexpressing adenomas (1.5 ± 0.21).
- NIR fluorescence demonstrated 100% sensitivity and specificity in detecting margin neoplasm, outperforming surgeon's visual assessment.
- NIR fluorescence accurately predicted postoperative MRI findings in 78% of FRα-overexpressing patients.
Conclusions:
- Preoperative administration of folate-tagged NIR dye enables robust visualization of NF pituitary adenomas.
- NIR fluorescence imaging offers superior detection capabilities compared to standard white-light visualization.
- This technology holds potential for improving gross-total resection rates in NF pituitary adenomas.
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