Binding interactions of vancomycin tracers with a bacterial cell wall peptidoglycan analogue.

Binding interactions between several vancomycin tracers and (N,N'-diacetyl)KDADA in solution were evaluated in a competition format using a surface plasmon resonance instrument. Tracers derivatized from the carboxy terminus or the N-vancosaminyl sugar moiety of vancomycin bind the peptide with an affinity similar to that of underivatized vancomycin. In contrast, N-methylleucyl derivatized vancomycin tracers bind the peptide with a reduced affinity relative to vancomycin.

Investigations into self-association of vancomycin covalent dimers using surface plasmon resonance technology.

Covalent dimers of vancomycin linked through the vancosamine sugar moieties of the glycopeptide antibiotic have been synthesized in one step in 67-69% yield. The propensity for self-association of these and related vancomycin covalent dimers is evaluated using surface plasmon resonance technology.

Structure-binding relationships for the interaction between a vancomycin monoclonal antibody Fab fragment and a library of vancomycin analogues and tracers.

A series of vancomycin analogues and tracers were synthesized, and their binding interactions with an anti-vancomycin Fab fragment were evaluated under mass transport limiting conditions using surface plasmon resonance detection. Differences observed in binding interactions were utilized to define the vancomycin structural elements critical for antibody recognition. Major structural regions of vancomycin shown to play an important role in anti-vancomycin Fab fragment recognition include two sugar moieties and one chlorinated phenyl ring. The N-methylleucyl residue, the carboxy terminal residue, and residues in the peptide-binding region of vancomycin have minimal impact on the anti-vancomycin Fab fragment/vancomycin binding interaction. The selection of an antibody with such binding properties plays a critical role in the development of a vancomycin immunoassay that employs stable calibrators and controls.

Development of a quantitative vancomycin immunoassay for the Abbott AxSYM analyzer.

A novel fluorescence polarization immunoassay for vancomycin on Abbott AxSYM analyzer is described. The immunoassay allows for the accurate quantification of vancomycin in the presence of the crystalline degradation product (CDP). It displays dilution linearity from 1.0 microg/ml to 100.0 microg/ml, coefficients of variation ranging from 2.94% to 4.26%, recovery from 98% to 105%, and a sensitivity of <2.0 microg/ml. The assay demonstrates no cross-reactivity to crystalline degradation product, and to commonly-prescribed and over-the-counter drugs, as well as a minimum interference from endogenous substances.

Change induced by radiation therapy in FDG uptake in normal and malignant structures of the head and neck: quantitation with PET.

PURPOSE: To quantitate the changes induced in uptake of the glucose analog 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in normal structures in the head and neck and compare these to the change in uptake in malignant structures in patients with head and neck tumors undergoing radiation therapy. MATERIALS AND METHODS: Eleven patients with biopsy-confirmed squamous cell carcinoma of the head and neck were studied before, during, and after a 6-week course of radiation therapy with positron emission tomography (PET)-FDG imaging. A ratio of FDG uptake in the structure compared with that in the cerebellum (termed metabolic ratio) within and outside of the field of radiation was determined in the adenoids; lingual and palatine tonsils; parotid, submandibular, and sublingual glands; and nasal turbinates, soft palate, and gingiva. RESULTS: The average metabolic ratio in the tonsils, nasal turbinates, soft palate, and gingiva did not change significantly with treatment. CONCLUSION: FDG uptake in normal structures does not change with radiation therapy. This fact is in marked contrast to the FDG uptake in squamous cell carcinomas in the head and neck, which decrease dramatically with treatment (P < .005).

Imaging of pulmonary mass lesions with whole-body positron emission tomography and fluorodeoxyglucose.

BACKGROUND: The clinical staging and management of both primary and metastatic lung lesions depends on accurate imaging techniques. Biochemical imaging with positron emission tomography, (PET), and the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose, (FDG), complements anatomic imaging with conventional radiologic methods. METHODS: A new "whole-body" PET FDG technique that produces two-dimensional, nontomographic and tomographic longitudinal images of the entire body has been developed at UCLA. Sixteen patients with known pulmonary nodules who had undergone thoracic computed tomography (CT) were studied with whole-body PET FDG imaging at the UCLA Medical Center. RESULTS: This PET FDG imaging method identified metabolically active tumor foci in all eight patients with bronchogenic carcinomas, four patients with metastatic lesions to the thorax, and two patients with Hodgkin disease. All diagnoses were confirmed histologically. Additionally, the PET FDG technique detected extrathoracic metastases in 4 of 16 patients. Thoracic CT was not diagnostic of neoplasm in two of the eight patients with bronchogenic carcinomas. In one patient with an ACTH-producing bronchial carcinoid, the lesion ultimately was detected on high-resolution CT but was not metabolically active on PET FDG imaging. CONCLUSIONS: This is the first report of whole-body PET FDG imaging in patients with thoracic lesions. PET FDG imaging accurately detected metabolically active tumor (both intrathoracic and extrathoracic) in patients with bronchogenic carcinoma, pulmonary metastatic disease, and Hodgkin lymphoma. Because lung cancer is characteristically a multisystem disease, this whole-body PET FDG technique has significant implications for treatment planning.

Extracranial head and neck: PET imaging with 2-[F-18]fluoro-2-deoxy-D-glucose and MR imaging correlation.

The aim of this study was to define and quantitate the normal anatomy of the extracranial head and neck with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). This information was used to study 12 patients with primary squamous cell carcinomas. In all cases, the lymphoid tissue of the Waldeyer ring and the palatine and lingual tonsils could be differentiated from the airway, striated muscle, osseous structures, and salivary glands. Striated muscle had markedly less activity than lymphoid or salivary gland tissue. In the 12 patients with primary tumors, FDG PET depicted the tumor as an area of increased activity significantly higher than that of normal tissue. In one instance, FDG PET allowed detection of a tumor not seen at magnetic resonance (MR) imaging or computed tomography. Of the 34 lymph nodes positive for carcinoma, 24 were positive according to MR size criteria and 25 were detected with FDG PET. FDG PET allowed detection of three nonenlarged metastatic nodes that were negative at MR imaging.