In Vivo Detection of Small Subsurface Melanomas in Athymic Mice Using Noninvasive Fiber Optic Confocal Imaging

Abstract

Fiber optic confocal imaging, following intravenous administration of fluorescently labeled antibodies and Texas Red-dextran, enabled in vivo detection of melanoma and surrounding blood vessels in athymic mice. Human melanoma cells (three cell lines) and cultured normal human skin cells were implanted intradermally into the haunch skin of anesthetized athymic BALB/C mice and allowed to grow to a maximum size of 2 mm diameter. Using three different fluorescein-isothiocyanate-labeled antimelanoma antibodies, single channel confocal images of melanoma cells were obtained in vivo. Using noninvasive techniques, the overall in vivo melanoma detection rate for tumors within 0.2 mm of the skin surface was 84% (27 of 32 tumors). Normal cultured human skin cells were found to have little or no fluorescence after administration of the fluorescein-isothiocyanate-labeled antibodies and tumors were not labeled by an isotype control antibody. Dual channel imaging of the implanted melanoma tumor and surrounding dermal vasculature in vivo showed increased blood vessel density at the melanoma site. Conventional immunoperoxidase histology confirmed that fiber optic confocal imaging was able to detect melanoma tumors up to 0.2 mm below the skin surface, in vivo.

In vivo fluorescence confocal microscopy: indocyanine green enhances the contrast of epidermal and dermal structures

“…In a mouse model, fluorescein-labeled antibodies have already been shown to successfully detect melanoma cells in vivo. 31 And recently, a topical formulation of ICG has also been prepared by Ra et al to evaluate its penetration properties into living human and mouse skin. 32 Using a handheld dualaxis confocal microscope, this group demonstrated that their ICG cream formulation readily penetrated the stratum corneum.…”

A Far-red Fluorescent Contrast Agent to Image Epidermal Growth Factor Receptor Expression

“…In addition, with the development of fiber-based in vivo confocal microscopes (39)(40)(41)(42)(43)(44), including the commercially available fiber-based confocal fluorescence microscopes produced by OptiScan Imaging Limited (Melbourne, Victoria, Australia) and Mauna Kea Technologies (Paris, France), the contrast agent could be used to provide additional signal for imaging applications to the epithelial layer in vivo to allow for diagnosis of abnormal tissue.…”

Confocal Laser Endomicroscopy: Applications in Clinical and Translational Science—A Comprehensive Review

“…Every organ that can be accessed in diagnostic or therapeutic medicine may be subject to CLE examination. In fact, one of the first human trials has been conducted in dermatology with a scanner later used for eCLE [73,74]. After first studies using pCLE [75] or eCLE/FIVE1 [76] for imaging of tissue excised from the urinary bladder, pCLE has been evaluated for onsite diagnosis in urology [77].…”