Estimation of detection limits of a clinical fluorescence optical mammography system for the near-infrared fluorophore IRDye800CW: phantom experiments

Abstract

To evaluate if clinical fluorescence imaging of IRDye800CW is feasible on our fluorescence optical mammography system by estimating detection limits assessed by breast-cancer-simulating phantom experiments. Phantoms (2.1 cm 3 , 0.9 cm 3 ) with IRDye800CW concentrations of 0.5 to 120 nM were suspended in a 550 cm 3 measurement cup containing 507 surface-mounted source and detector fibers. The cup was filled with optical matching fluid containing IRDye800CW concentrations of 0, 5, 10, or 20 nM. Tomographic fluorescence images were acquired by exciting IRDye800CW at 730 nm; wavelengths above 750 nm were filtered. Signal intensities were calculated over a volume of interest corresponding to the size and location of the phantom in the reconstructed images. Correlations (R 2 ) were calculated, and detection limits with associated upper 95% prediction interval were estimated. Between-day reproducibility was assessed with intraclass correlation coefficients (ICC). Fluorescent intensities were strongly correlated with phantom IRDye800CW concentrations (R 2 ∶0.983 to 0.999). IRDye800CW detection limits ranged from 0.14 to 2.46 nM (upper 95% prediction limit 4.63 to 18.63 nM). ICC ranged from 0.88 to 1.00. The estimated detection limits for IRDye800CW were in the low-nanomolar range. These results support the start of clinical trials to evaluate the fluorescence optical mammography system using IRDye800CW labeled breast cancer targeting ligands.

Monoclonal antibody-based molecular imaging strategies and theranostic opportunities

“…For optical fluorescence imaging popular imaging agents include near-infrared fluorophores such as IRDye 800CW 18, Ag 2 S quantum dots 19 and the FDA-approved indocyanine green 20.…”

Recent developments in multimodality fluorescence imaging probes

“…Among them, indocyanine green (ICG) is the only NIRF dye approved by Food and Drug Administration (FDA) in the United States for clinical use 19 , 20 . Another NIR dye, IRDye 800CW, has entered clinical trials 21 . In addition, NIRF imaging in the second biological window (1000—1400 nm), also named over-thousand near-infrared (OTN) imaging, has attracted significant attention in in vivo imaging applications due to its even deeper tissue penetration, higher image contrast, and reduced phototoxicity and photobleaching 22 .…”

Fluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging

“…Cyanines display low toxicity and therefore are commonly used in biomedical applications. Notably, indocyanine green (ICG) and fluorescein are among the only fluorescent indicators approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA), and IRDye800 CW is the subject of several clinical trials [13,94,95]. Possible functionalization on terminal nitrogen atoms and on the central methine group is favored for introduction of bioconjugation links and radiolabeling sites.…”