FDA-approved Dye Research Articles

Abstract SY03-01: Molecular imaging with cellular resolution and molecular specificity using miniaturized microscopes

Abstract The earliest malignant lesions are microscopic in size and may be characterized by abnormal cell surface markers and disrupted microanatomy. The challenge for early detection of cancer is effectively using these features to localize and characterize those early lesions that are likely to progress. For cancers of the gastrointestinal (GI) tract there are some predisposing conditions that identify high-risk regions, and justify microscopic analyses for detection, diagnosis and guided biopsy of small, early lesions. In addition, microscopic analyses are used for detection of tumor margins in resection of skin and breast cancer and may have utility in resection of cancers. Micro-optical designs are enabling the development of miniaturized microscopes that can reach inside the body to interrogate disease states with cellular resolution. In combination with molecular probes such instruments can be used to interrogate suspect lesions for early signs of malignancy and to determine if margins are clear. To enable molecular imaging with cellular resolution, we have developed miniaturized confocal fluorescence microscopes that are based on a dual-axis architecture. The dual-axis design enables the use of low numerical aperture lenses and a folded light path that is amenable to a small form factor and post objective scanning in the scan head. The design features of this microscope included axial and transverse resolutions comparable to that used by pathologists (5 µM), and a 0.5 × 0.5 × 0.5 mm 3-D field of view in an instrument that has an external diameter compatible with use in an endoscope for GI cancers, and that can reach into small cavities for guided resections. The first dual-axis confocal (DAC) microscope that has been used in a clinical study in the colon with these capabilities has a 5-mm external diameter and an excitation wavelength of 780 nm. To enable early detection we have developed and tested a number of optical probes for use as molecular markers, and evaluated FDA-approved dyes as contrast for analysis of microanatomy. Studies in animals and man demonstrated the ability to observe microanatomy and discriminate malignant tissue from surrounding normal tissues. A wide variety of fluorescent agents are being developed and tested for cancer detection using macroscopic approaches. These agents can be detected at the cellular level with miniaturized microscopes for complementary analyses. Placement of the microscope can be guided by the macroscopic images, and the microscopic data can be used to substantiate the images. We have targeted surface markers and the cytoplasmic enzyme Cox-2 in these studies. We fitted the DAC microscopes with a needle lens to reach deep into the tissues and this instrument has been evaluated for guided resections of medulloblastoma in preclinical studies. The next-generation instruments have a smaller form factor and are designed for multispectral capabilities and faster scan times. This will increase their utility with increased access to tissues sites and multiplexed in vivo assays. The co-development of molecular probes and micro-optical instruments to visualize cancer may improve detection of cancer, and can be used to assess therapeutic outcome. Advances in in vivo microscopy could lead to a fundamental shift in the diagnostic paradigm from biopsy with conventional histopathology to performance of point-of-care morphologic diagnosis using in vivo microscopic pathology. These technologies are closing the gap between the patient and the diagnostic event, and will have major ramifications for the training of future physicians to interpret real-time in vivo microscopic molecular data, and will advance the emerging field of telepathology. One of the features of multimodality molecular imaging is reaching across a range of scales from microscopic, cellular resolution, to macroscopic, whole body, imaging and new tools with microscopic capabilities are necessary to achieve these aims Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY03-01. doi:10.1158/1538-7445.AM2011-SY03-01

Indocyanine-green-embedded PEBBLEs as a contrast agent for photoacoustic imaging

Nanoparticles 100 nm in diameter containing indocyanine green (ICG) have been developed as a contrast agent for photoacoustic (PA) imaging based on (photonic explorers for biomedical use by biologically localized embedding PEBBLE) technology using organically modified silicate (ormosil) as a matrix. ICG is an FDA-approved dye with strong optical absorption in the near-infrared (NIR) region, where light can penetrate deepest into biological tissue. A photoacoustic imaging system was used to study image contrast as a function of PEBBLE concentration in phantom objects. ICG-embedded ormosil PEBBLEs showed improved stability in aqueous solution compared with free ICG dye. The particles were conjugated with HER-2 antibody for breast cancer and prostate cancer cell targeting. Initial in vitro characterization shows high contrast and high efficiency for binding to prostate cancer cells. ICG can also be used as a photosensitizer (generating toxic oxygen by illumination) for photodynamic therapy. We have measured the photosensitization capability of ICG-embedded ormosil nanoparticles. This feature can be utilized to combine detection and therapeutic functions in a single agent.

Severe allergic blepharoconjunctivitis induced by a dye for eyelashes and eyebrows

Purpose: To report a case of severe allergic blepharoconjunctivitis induced by a dye for eyebrows and eyelashes. Methods: A 38-year-old healthy female was examined one day after dyeing her eyebrows and eyelashes with a black cream dye intended for this purpose (FDA-approved). The patient complained of severe eye itching, redness, and epiphora. Results: Vision was 20/40 in both eyes; a moderate edema of the eyebrows and eyelid margins was noted. The conjunctiva was severely hyperemic with papillary reaction and chemosis. The corneas, anterior chambers, irides, lenses, and posterior segments were normal. The patient was treated with Dexamethasone 0.1% and ocular lubrication. After five days of treatment, the ocular symptoms improved, her vision returned to 20/20 in both eyes, and the ocular examination was within normal limits. Conclusion: FDA-approved dyes for eyebrows and eyelashes can sometimes irritate the ocular surface.