Fluorescence Imaging for Cancer Screening and Surveillance

Tipirneni, Kiranya E.; Rosenthal, Eben L.; Moore, Lindsay; Haskins, A. D.; Udayakumar, Neha; Jani, Aditi; Carroll, William R.; Morlandt, Anthony B.; Bogyo, Matthew; Rao, Jianghong; Warram, Jason M.

doi:10.1007/s11307-017-1050-5

Cited by 50 publications

(32 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These methods have been found safe and effective for a wide range of common neoplasms, including CNS tumors, abdominal cancers, and soft-tissue malignancies. [5][6][7][8][9][10] In these reports, IMI has been found to improve complete resection, lymph node identification, and margin assessment.…”

Section: Introductionmentioning

confidence: 95%

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

et al. 2018

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is the number one cancer killer in the United States. Despite attempted curative surgical resection, nearly 40% of patients succumb to recurrent disease. High recurrence rates may be partially explained by data suggesting that 20% of NSCLC patients harbor synchronous disease that is missed during resection. In this report, we describe the use of a novel folate receptor-targeted near-infrared contrast agent (OTL38) to improve the intraoperative localization of NSCLC during pulmonary resection. Using optical phantoms, fluorescent imaging with OTL38 was associated with less autofluorescence and greater depth of detection compared to traditional optical contrast agents. Next, in in vitro and in vivo NSCLC models, OTL38 reliably localized NSCLC models in a folate receptor-dependent manner. Before testing intraoperative molecular imaging with OTL38 in humans, folate receptor-alpha expression was confirmed to be present in 86% of pulmonary adenocarcinomas upon histopathologic review of 100 human pulmonary resection specimens. Lastly, in a human feasibility study, intraoperative molecular imaging with OTL38 accurately identified 100% of pulmonary adenocarcinomas and allowed for identification of additional subcentimeter neoplastic processes in 30% of subjects. This technology may enhance the surgeon's ability to identify NSCLC during oncologic resection and potentially improve long-term outcomes.

show abstract

Section: Introductionmentioning

confidence: 95%

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Various tumor-targeted near-infrared (NIR) fluorescence agents have been successfully studied in clinical trials [3][4][5][6]. Moreover, there is great potential for a broad range of clinical applications besides oncology, such as infectious and inflammatory diseases [7]. Consequently, new study groups, industry as well as hospitals are increasingly interested to explore and implement this technology in clinical care.…”

Section: Introductionmentioning

confidence: 99%

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

et al. 2018

View full text Add to dashboard Cite

Purpose: Intraoperative fluorescence imaging (FI) is a promising technique that could potentially guide oncologic surgeons toward more radical resections and thus improve clinical outcome. Despite the increase in the number of clinical trials, fluorescent agents and imaging systems for intraoperative FI, a standardized approach for imaging system performance assessment and post-acquisition image analysis is currently unavailable. Procedures: We conducted a systematic, controlled comparison between two commercially available imaging systems using a novel calibration device for FI systems and various fluorescent agents. In addition, we analyzed fluorescence images from previous studies to evaluate signal-to-background ratio (SBR) and determinants of SBR. Results: Using the calibration device, imaging system performance could be quantified and compared, exposing relevant differences in sensitivity. Image analysis demonstrated a profound influence of background noise and the selection of the background on SBR. Conclusions: In this article, we suggest clear approaches for the quantification of imaging system performance assessment and post-acquisition image analysis, attempting to set new standards in the field of FI.

show abstract

“…Results presented in Figure 4 further highlight the in vivo use of IR-780 dye-loaded rHDL NPs and the ability to be successfully localized in tumor tissue after application of US-stimulated drug delivery. Given the ever-expanding role of fluorescence imaging in human oncology 39 , 40 , the prospect of using this modality for monitoring US-stimulated drug delivery is encouraging. Future work will investigate the use of US-stimulated drug delivery of rHDL NPs preloaded with both an anticancer drug and IR-780 dye.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles

Xiong¹,

Sabnis²,

Sirsi³

et al. 2017

Nanotheranostics

View full text Add to dashboard Cite

The abnormal tumor vasculature and the resulting abnormal microenvironment are major barriers to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer agents. Reconstituted high-density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via their overexpressed scavenger receptor type B1 (SR-B1) receptor. The goal of this study is to investigate the potential of noninvasive US therapy to further improve delivery and tumor uptake of the payload from rHDL NPs, preloaded with an infrared dye (IR-780), aimed to establish a surrogate chemotherapeutic model with optical localization. Athymic nude mice were implanted orthotopically with one million breast cancer cells (MDA-MB-231/Luc). Three weeks later, animals were divided into seven groups with comparable mean tumor size: control, low, moderate, and high concentration of rHDL NPs alone groups, as well as these three levels of rHDL NPs plus US therapy groups (N = 7 to 12 animals per group), where low, moderate and high denote 5, 10, and 50 µg of the IR-780 dye payload per rHDL NP injection, respectively. The US therapy system included a single element focused transducer connected in series with a function generator and power amplifier. A custom 3D printed cone with an acoustically transparent aperture and filled with degassed water allowed delivery of focused US energy to the tumor tissue. US exposure involved a pulsed sequence applied for a duration of 5 min. Each animal in the US therapy groups received a slow bolus co-injection of MB contrast agent and rHDL NPs. Animals were imaged using a whole-body optical system to quantify intratumoral rHDL NP accumulation at baseline and again at 1 min, 30 min, 24 h, and 48 h. At 48 h, all animals were euthanized and tumors were excised for ex vivo analysis. We investigated a noninvasive optical imaging method for monitoring the effects of US-stimulated drug delivery of IR-780 dye-loaded rHDL NPs in living animals. No change in optical imaging data was found in the control animals. However, there was considerable dye accumulation (surrogate drug) within 48 h in the low (5 µg), moderate (10 µg), and high (50 µg) rHDL NP concentration-dosed group animals (p < 0.09). With US therapy added to the experimental protocol, there was an additional and significant increase in local tumor drug uptake at 48 h (p < 0.02). Optical image data collected from ex vivo tumor samples confirmed tumor retention of the IR-780 dye-loaded rHDL NPs and correlated positively with in vivo optical imaging results (R2 > 0.69, p < 0.003). IR-780 dye extraction from the tumor tissue samples confirmed the in vivo and ex vivo US therapy findings. Overall, the addition of US therapy considerably improved local rHDL NP accumulation in tumor tissue. This study concludes that US-mediated drug delivery can facilitate tumor uptake of rHDL NPs and more research is warranted to optimize the drug dos...

show abstract

Fluorescence Imaging for Cancer Screening and Surveillance

Cited by 50 publications

References 84 publications

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles

Contact Info

Product

Resources

About