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.

Abstract

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.

Related Concept Videos

Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
66.5K
Sensitivity, Specificity, and Predicted Value01:13

Sensitivity, Specificity, and Predicted Value

In healthcare diagnostics, laboratory tests play a crucial role in identifying and diagnosing a wide range of medical conditions. However, interpreting test results is not always straightforward. An abnormal test result does not always confirm the presence of a disease, just as a normal result does not guarantee its absence. To assess the reliability of these diagnostic tools, healthcare practitioners rely on two key statistical indicators: sensitivity and specificity.
Sensitivity is the...
1.4K
Hormones of the Pituitary Gland01:27

Hormones of the Pituitary Gland

The small, pea-sized pituitary gland is located at the base of the brain. It is crucial in regulating various bodily functions, from growth to reproduction. The gland is divided into the anterior lobe and the posterior lobe. The secretory cell clusters in the pars distalis of the anterior pituitary lobe are controlled by hypothalamic regulators and synthesize six primary hormones.
The most abundantly secreted hormone from the anterior lobe is the growth hormone, which controls overall growth by...
10.6K
The Pituitary Gland01:17

The Pituitary Gland

The pituitary is a small endocrine organ in the sphenoid bone under the hypothalamus. Primarily, the pituitary in adults has two distinct anatomical and functional regions— the anterior and posterior lobes. During human fetal development, a third pituitary gland region called the pars intermedia atrophies and disappears. However, some of its cells migrate and exist adjacent to the anterior pituitary in adults.
11.0K
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.7K
Imaging Biological Samples with Optical Microscopy01:18

Imaging Biological Samples with Optical Microscopy

Optical microscopy uses optic principles to provide detailed images of samples. Antonie van Leeuwenhoek designed the first compound optical microscope in the 17th century to visualize blood cells, bacteria, and yeast cells. In 1830, Joseph Jackson Lister created an essentially modern light microscope. The 20th century saw the development of microscopes with enhanced magnification and resolution.
In optical microscopy, the specimen to be viewed is placed on a glass slide and clipped on the stage...
11.0K