Prediction of optimal contrast times post-imaging agent administration to inform personalized fluorescence-guided surgery

Sadeghipour, Negar; Rangnekar, Aakanksha; Folaron, Margaret R.; Strawbridge, Rendall R.; Samkoe, Kimberley S.; Davis, Scott C.; Tichauer, Kenneth M.

doi:10.1117/1.jbo.25.11.116005

Cited by 8 publications

(9 citation statements)

References 37 publications

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“…Dose and time play an important role in determining tumor contrast and can be optimized to strengthen the predictive value of an FGS agent. − Since fluorescence emits low-energy photons that limit the measurement of absolute drug concentration, we radiolabeled MMC(FNIR-Tag)-TOC with the γ-emitting radionuclide 67 Ga to overcome attenuation and scattering phenomena. , We injected increasing doses (2, 5, and 10 nmol) of 67 Ga-MMC(FNIR-Tag)-TOC into nude mice with NCI-H69 xenografts, which endogenously express SSTR2, and imaged at 3 and 24 h p.i. Figure A qualitatively illustrates that tumor uptake increased as a function of dose while decreasing with time both at the macro- and mesoscopic scales; importantly, tumor signal was the highest among nonclearance organs regardless of dose or imaging time.…”

Section: Resultsmentioning

confidence: 99%

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

et al. 2022

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Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced nearinfrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue. In vitro studies showed that the optimized fluorescent conjugate MMC-(FNIR-Tag)-TOC bound primarily via somatostatin receptor subtype-2 (SSTR2), whereas its negatively charged counterpart with IRDye 800CW had higher off-target binding. NIRF imaging in cell line-and patient-derived xenograft models revealed markedly higher tumor contrast with MMC(FNIR-Tag)-TOC, which was attributed to increased tumor specificity. Ex vivo staining of surgical biospecimens from primary and metastatic tumors, as well as involved lymph nodes, demonstrated binding to human tumors. Finally, in an orthotopic tumor model, a simulated clinical workflow highlighted our unique ability to use standard preoperative nuclear imaging for selecting patients likely to benefit from SSTR2-targeted FGS. Our findings demonstrate the translational potential of MMC(FNIR-Tag)-TOC for intraoperative imaging and suggest broad utility for using FNIR-Tag in fluorescent probe development.

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Section: Resultsmentioning

confidence: 99%

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

et al. 2022

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“…Peptide-based fluorescent probes such as the ones in this study are attractive for a fluorescence-guided surgery because they have higher fluorescence density at the target site and much shorter blood clearance times than analogous antibody probes. 59 Analysis of the PAI data permitted determination of BP as a quantitative measure of integrin targeting effectiveness for each targeted probe in the tumor and muscle tissue. The pixelated maps of BP (Figure 4) reflect tumor-to-tumor variation in average BP, and a heterogeneous spatial distribution of BP within each tumor.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The high tumor-to-background ratios facilitated a mock surgical procedure that excised the subcutaneous tumors. Peptide-based fluorescent probes such as the ones in this study are attractive for a fluorescence-guided surgery because they have higher fluorescence density at the target site and much shorter blood clearance times than analogous antibody probes . Analysis of the PAI data permitted determination of BP as a quantitative measure of integrin targeting effectiveness for each targeted probe in the tumor and muscle tissue.…”

Section: Discussionmentioning

confidence: 99%

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Gamage

Schreiber

et al. 2021

ACS Omega

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Previous work has shown that the sterically shielded near-infrared (NIR) fluorescent heptamethine cyanine dye, s775z, with a reactive carboxyl group produces fluorescent bioconjugates with an unsurpassed combination of high photostability and fluorescence brightness. This present contribution reports two new reactive homologues of s775z with either a maleimide group for reaction with a thiol or a strained alkyne group for reaction with an azide. Three cancer-targeting NIR fluorescent probes were synthesized, each with an appended cRGDfK peptide to provide selective affinity for integrin receptors that are overexpressed on the surface of many cancer cells including the A549 lung adenocarcinoma cells used in this study. A set of cancer cell microscopy and mouse tumor imaging experiments showed that all three probes were very effective at targeting cancer cells and tumors; however, the change in the linker structure produced a statistically significant difference in some aspects of the mouse biodistribution. The mouse studies included a mock surgical procedure that excised the subcutaneous tumors. A paired-agent fluorescence imaging experiment co-injected a binary mixture of targeted probe with 850 nm emission, an untargeted probe with 710 nm emission and determined the targeted probe’s binding potential in the tumor tissue. A comparison of pixelated maps of binding potential for each excised tumor indicated a tumor-to-tumor variation of integrin expression levels, and a heterogeneous spatial distribution of integrin receptors within each tumor.

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“…, where I FL ALA and I FL Control are the averaged fluorescence intensities in the imaged ALA-applied area and the control area, alongside their respective variances σ 2 ALA and σ 2 Control . 13 The CVR metric is preferred over standard signal-to-noise calculations as it provides a better estimation of fluorescence contrast performance by accounting for the signal and variance of both the fluorescence and control regions in the metric calculation. 14 3 Results…”

Section: Methodsmentioning

confidence: 99%

Lighting gel filters as low-cost alternatives for fluorescence imaging and optical system design

et al. 2022

Self Cite

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Lighting gel filters are widely used in commercial industries, but their adoption in scientific applications is limited, despite their low cost and form factor advantages. Here, we compare the optical performance of lighting gel filters to commonly used dielectric and colored glass filters in terms of absorbance spectra, passband transmission, angle of incidence dependence, autofluorescence, and photostability. Further comparison is performed in both preclinical and clinical imaging applications. The results show that gel filters might be a superior filter choice in several optical systems, including compact designs and fluorescence imaging applications. Compact designs using gel filters could have a significant advantage for applications such as point-of-care diagnostics, smartphone device add-ons, and single-use fluorescent assays.

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Prediction of optimal contrast times post-imaging agent administration to inform personalized fluorescence-guided surgery

Cited by 8 publications

References 37 publications

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Lighting gel filters as low-cost alternatives for fluorescence imaging and optical system design

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