CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern.

X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task. Therefore, we developed a new class of nanosized cathepsin-targeted activity-based probes (ABPs) for functional CT imaging of cancer. ABPs are small molecules designed to covalently modify enzyme targets in an activity-dependent manner. Using a CT instrument, these novel probes enable detection of the elevated cathepsin activity within cancerous tissue, thus creating a direct link between biological processes and imaging signals. We present the generation and biochemical evaluation of a library of ABPs tagged with different sized gold nanoparticles (GNPs), with various ratios of cathepsin-targeting moiety and a combination of different polyethylene glycol (PEG) protective layers. The most potent and stable GNP-ABPs were applied for noninvasive cancer imaging in mice. Surprisingly, detection of CT contrast from the tumor had reverse correlation to GNP size and the amount of targeting moiety. Interestingly, TEM images of tumor sections show intercellular lysosomal subcellular localization of the GNP-ABPs. In conclusion, we demonstrate that the covalent linkage is key for detection using low sensitive imaging modalities and the utility of GNP-ABPs as a promising tool for enzymatic-based CT imaging.

Oral syphilis lesions--a diagnostic approach and histologic characteristics of secondary stage.

Syphilis is among the oldest recognized sexually transmitted diseases. In the past decade, its incidence has risen significantly in the developed world. Oral syphilitic lesions, the most common extragenital sign of infection, are a diagnostic challenge to dentists, who are usually the first to examine the oral lesions. Biopsies are occasionally the first examination performed, but histologic findings are considered nonspecific. We present two new cases as well as an additional 25 published cases, suggesting that plasma cell arteritis and plasma cell neuritis is a combination that has not been reported in any other pathologic condition of the oral cavity and may be specific enough to direct the clinician toward a diagnosis of syphilis prior to clinical confirmation.

Tissue reaction to liquid silicone simulating low-grade liposarcoma following lip augmentation.

We report the case of a 32-year-old woman who underwent silicone injection into the upper lip 2 years prior to presenting with masses clinically suspicious for tumor and interpreted on biopsy as low-grade liposarcoma. Lack of pre-operative history of silicone injection almost led to unnecessary surgery. This complicated situation may arise when reaction to liquid or gel silicone histologically closely simulates a low-grade liposarcoma. Clinical and pathological correlations are of critical assistance in making the correct pre-operative diagnosis and avoiding unnecessary traumatic surgical intervention.