Abstract
.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, -MMC(IR800)-TOC, was injected into mice () 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 (, 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 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 (, ; ; ).Conclusion: The innovative OnLume NIRF imaging system enhanced the evaluation of -MMC(IR800)-TOC in tumor models. These components comprise a promising drug–device combination for FGS in patients with SSTR2-expressing tumors.
Highlights
Surgery is an essential treatment option for most solid tumors and can be curative if complete resections are achieved.[1]
fluorescence-guided surgery (FGS) relies on the combined administration of a fluorescent contrast agent and its subsequent detection with an imaging system; translational research strategies may consist of drug only, device only, or drug–device combinations.[3,4]
In addition to use for intraoperative applications, such as lymphatic mapping and sentinel lymph node biopsy, indocyanine green (ICG) has been used to assess the clinical performance of newly developed imaging systems that seek regulatory approval for human use.[6]
Summary
Surgery is an essential treatment option for most solid tumors and can be curative if complete resections are achieved.[1] To improve intraoperative detection of tumors and potentially improve surgical outcomes in cancer patients, surgeons increasingly use fluorescence-guided surgery (FGS) to augment feedback obtained through standard visual and tactile cues.[2] FGS relies on the combined administration of a fluorescent contrast agent (i.e., drug) and its subsequent detection with an imaging system (i.e., device); translational research strategies may consist of drug only, device only, or drug–device combinations.[3,4]. The introduction of tumor-targeted FGS drugs into clinical trials has shown that cancer-specific agents may improve the predictive value of the fluorescent signal and could play an important role in cancer treatments due to their potential to enhance complete resection rates and patient outcomes.[9,10,11,12,13,14] approaches that simultaneously develop tumor-specific drugs and sensitive imaging devices are needed to assess the accuracy of FGS for tumor localization and determine the translational potential of emerging technologies
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