Related Experiment Video
Updated: Nov 26, 2025
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Development of a drug-device combination for fluorescence-guided surgery in neuroendocrine tumors
Servando Hernandez Vargas1, Christie Lin2, Julie Voss1
1The University of Texas Health Science Center at Houston, The Brown Foundation Institute of Molecula, United States.
Significance:
The use of cancer-targeted contrast agents in fluorescence-guided surgery (FGS) has the potential to improve intraoperative visualization of tumors and surgical margins. However, evaluation of their translational potential is challenging.
Aim:
We examined the utility of a somatostatin receptor subtype-2 (SSTR2)-targeted fluorescent agent in combination with a benchtop near-infrared fluorescence (NIRF) imaging system to visualize mouse xenografts under conditions that simulate the clinical FGS workflow for open surgical procedures.
Approach:
The dual-labeled somatostatin analog, Ga67-MMC(IR800)-TOC, was injected into mice (n = 24) implanted with SSTR2-expressing tumors and imaged with the customized OnLume NIRF imaging system (Madison, Wisconsin). In vivo and ex vivo imaging were performed under ambient light. The optimal dose (0.2, 0.5, and 2 nmol) and imaging time point (3, 24, 48, and 72 h) were determined using contrast-to-noise ratio (CNR) as the image quality parameter. Video captures of tumor resections were obtained to provide an FGS readout that is representative of clinical utility. Finally, a log-transformed linear regression model was fitted to assess congruence between fluorescence readouts and the underlying drug distribution.
Results:
The drug-device combination provided high in vivo and ex vivo contrast (CNRs > 3, except lung at 3 h) at all time points with the optimal dose of 2 nmol. The optimal imaging time point was 24-h post-injection, where CNRs > 6.5 were achieved in tissues of interest (i.e., pancreas, small intestine, stomach, and lung). Intraoperative FGS showed excellent utility for examination of the tumor cavity pre- and post-resection. The relationship between fluorescence readouts and gamma counts was linear and strongly correlated (n = 334, R2 = 0.71; r = 0.84; P < 0.0001).
Conclusion:
The innovative OnLume NIRF imaging system enhanced the evaluation of Ga67-MMC(IR800)-TOC in tumor models. These components comprise a promising drug-device combination for FGS in patients with SSTR2-expressing tumors.
Insights
This study demonstrates a novel drug-device combination for fluorescence-guided surgery (FGS). The somatostatin receptor subtype-2 (SSTR2)-targeted agent and near-infrared fluorescence (NIRF) imaging system show promise for visualizing SSTR2-expressing tumors.
Area of Science:
- Oncology
- Medical Imaging
- Surgical Technology
Background:
- Fluorescence-guided surgery (FGS) utilizes cancer-targeted contrast agents for improved tumor visualization.
- Evaluating the translational potential of these agents in clinical settings remains a challenge.
Purpose of the Study:
- To assess the utility of a somatostatin receptor subtype-2 (SSTR2)-targeted fluorescent agent with a near-infrared fluorescence (NIRF) imaging system.
- To simulate clinical FGS workflow for open surgical procedures using mouse xenografts.
Main Methods:
- A dual-labeled somatostatin analog, Ga67-MMC(IR800)-TOC, was administered to mice with SSTR2-expressing tumors.
- Imaging was performed using the OnLume NIRF system, optimizing dose and time points based on contrast-to-noise ratio (CNR).
- Intraoperative video captures and regression analysis assessed FGS utility and drug distribution.
Main Results:
- The drug-device combination achieved high in vivo and ex vivo contrast (CNR > 3), with optimal imaging at 24-h post-injection (CNR > 6.5).
- FGS demonstrated excellent utility for tumor cavity assessment pre- and post-resection.
- A strong linear correlation (R²=0.71, r=0.84) was found between fluorescence readouts and gamma counts.
Conclusions:
- The OnLume NIRF imaging system effectively evaluated the Ga67-MMC(IR800)-TOC agent in preclinical models.
- This drug-device combination represents a promising approach for FGS in patients with SSTR2-expressing tumors.
