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Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate
Woo Kyung Moon1, Yuhui Lin, Terence O'Loughlin
1Center for Molecular Imaging Research,Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Abstract:
Fluorescence optical imaging technologies are currently being developed to image specific molecular targets in vivo. Detection technologies range from those providing microscopic detail to whole body imaging systems with potential clinical use. A number of target-specific near-infrared imaging probes have recently been developed to image receptors, antigens, and enzymes. The goal of the current study was to evaluate a new near-infrared (NIR) folate receptor (FR)-targeted imaging probe for its ability to improve detection of FR-positive cancers. We hypothesized that modification of folate would retain receptor affinity in vivo, despite the bulkier NIR fluorochrome, NIR2 (em = 682 nm). Cellular uptake of the NIR conjugates was significantly higher in FR-positive nasopharyngeal epidermoid carcinoma, KB cells, compared to FR-negative human fibrosarcoma, HT1080 cells. When tumors were implanted in vivo, equal-sized KB tumors showed a 2.4-fold higher signal intensity compared to HT1080 tumors (24 h). The maximum signal-to-background ratio (3-fold) was observed at 24 h in KB tumor. Injection of the unmodified NIR2 fluorochrome did not result in persistent contrast increases under similar conditions. Furthermore, tumor enhancement with the NIR2-folate probe persisted over 48 h and was inhibitable in vivo by administration of unlabeled folate. These results indicate that folate-modified NIR fluorochrome conjugate can be used for improved detection of FR-positive tumors.
Insights
A novel near-infrared (NIR) folate receptor (FR)-targeted imaging probe enhances detection of FR-positive cancers. This probe shows improved tumor signal intensity and persistence, aiding in early cancer diagnosis.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Optical Imaging
Background:
- Fluorescence optical imaging is advancing for in vivo molecular target detection.
- Near-infrared (NIR) imaging probes are crucial for visualizing specific biological targets.
- Folate receptors (FRs) are overexpressed in various cancers, making them attractive imaging targets.
Purpose of the Study:
- To evaluate a new NIR imaging probe targeting folate receptors (FRs).
- To assess the probe's efficacy in improving the detection of FR-positive cancers in vivo.
- To determine if folate modification retains receptor affinity despite a bulky fluorochrome.
Main Methods:
- Development of a NIR-conjugated folate imaging probe (NIR2-folate).
- In vitro cellular uptake studies using FR-positive (KB) and FR-negative (HT1080) cells.
- In vivo tumor imaging studies in animal models with implanted tumors.
- Assessment of signal intensity, signal-to-background ratio, and probe persistence.
Main Results:
- NIR2-folate showed significantly higher cellular uptake in FR-positive KB cells compared to FR-negative HT1080 cells.
- In vivo, KB tumors exhibited a 2.4-fold higher signal intensity than HT1080 tumors at 24 hours.
- The probe achieved a maximum 3-fold signal-to-background ratio at 24 hours and demonstrated persistent tumor enhancement for over 48 hours, inhibitable by unlabeled folate.
Conclusions:
- Folate-modified NIR fluorochrome conjugates effectively target FR-positive tumors.
- This NIR2-folate probe offers improved detection capabilities for FR-positive cancers.
- The probe's design shows promise for enhanced in vivo cancer imaging and diagnosis.