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Sapsford K.E.,Office of Science and Engineering Laboratories | Tezak Z.,Personalized Medicine | Kondratovich M.,Personalized Medicine | Pacanowski M.A.,U.S. Food and Drug Administration | And 2 more authors.
Therapeutic Delivery | Year: 2010

This article highlights a current US FDA perspective concerning the use of biomarker-based diagnostics for personalized medicine. Specifically, current biomarkers that have application for improving the benefit/risk profile of already approved drugs are discussed. The success of biomarkers for use in personalized medicine depends on many factors, including proper evaluation of the usefulness of the biomarker for assessing the event of interest, and the safety and effectiveness of the diagnostic device used to measure the biomarker, which includes appropriate analytical and clinical validation. These points along with the many regulatory concerns regarding co-labeling of drugs and devices and future aspects, such as co-development, will be discussed in this regulatory science focus. © 2010 Future Science Ltd.

Ardeshirpour Y.,National Institute of Child Health and Human Development | Chernomordik V.,National Institute of Child Health and Human Development | Hassan M.,National Institute of Child Health and Human Development | Hassan M.,Office of Science and Engineering Laboratories | And 4 more authors.
Clinical Cancer Research | Year: 2014

Purpose: Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors. Experimental Design: HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe inj ections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pretreatment size. Results: Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (~0.13 ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment), the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03 ns. Conclusions: The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients. © 2014 American Association for Cancer Research.

Sapsford K.E.,Office of Science and Engineering Laboratories | Blanco-Canosa J.B.,Scripps Research Institute | Dawson P.E.,Scripps Research Institute | Medintz I.L.,Center for Bio Molecular Science and Engineering
Bioconjugate Chemistry | Year: 2010

A simple bifunctional colorimetric/fluorescent sensing assay is demonstrated for the detection of HIV-1 specific antibodies. This assay makes use of a short peptide sequence coupled to an environmentally sensitive dye that absorbs and emits in the visible portion of the spectrum. The core peptide sequence is derived from the highly antigenic six-residue epitope of the HIV-1 p17 protein and is situated adjacent to a terminal cysteine residue which enables site-specific fluorescent labeling with Cy3 cyanine dye. Interaction of the Cy3-labeled p17 peptide with monoclonal anti-p17 antibody resulted in an up to 4-fold increase in dye absorption and greater than 5-fold increase in fluorescent emission, yielding a limit of detection as low as 73 pM for the target antibody. This initial study demonstrates both proof-of-concept for this approach and suggests that the resulting sensor could potentially be used as a rapid screening method for HIV-1 infection while requiring minimal equipment and reagents. The potential for utilizing this assay in simple field-portable point-of-care and diagnostic devices is discussed. © 2010 American Chemical Society.

Siegelman J.W.,Brigham and Womens Hospital | Supanich M.P.,Rush University Medical Center | Gavrielides M.A.,Office of Science and Engineering Laboratories
American Journal of Roentgenology | Year: 2015

OBJECTIVE. Pulmonary nodules of ground-glass opacity represent one imaging manifestation of a slow-growing variant of lung cancer. The objective of this phantom study was to quantify the effect of the radiation dose used for the examination (volume CT dose index [CTDIvol]), type of reconstruction algorithm, and choice of postreconstruction enhancement algorithms on the measurement error when assessing the volume of simulated lung nodules with CT, focusing on two radiodensity levels. MATERIALS AND METHODS. Twelve synthetic nodules of two radiodensities (?630 and ?10 HU), three shapes (spherical, lobulated, and spiculated), and two sizes (nominal diameters of 5 and 10 mm) were inserted into an anthropomorphic chest phantom and scanned with techniques varying in CTDIvol (from subscreening dose [0.8 mGy] to diagnostic levels [6.5 mGy]), reconstruction algorithms (iterative reconstruction and filtered back projection), and different postreconstruction enhancement algorithms. Nodule volume was measured from the resulting reconstructed CT images with a matched filter estimator. RESULTS. No significant over-or underestimation of nodule volume was observed across individual variables, with low percentage error overall (?1.4%) and for individual variables (range, ?3.4% to 0.4%). The magnitude of percentage error was also low (overall average percentage error < 6% and SD values < 4.5%) and for individual variables (absolute percentage error range 3.3-5.6%). No clinically significant differences were observed between different levels of CTDIvol, use of iterative reconstruction algorithms, or use of different postreconstruction enhancement algorithms. CONCLUSION. These results indicate that, if validated for other measurement tools and scanners, lung nodule volume measurements from scans acquired and reconstructed with significantly different acquisition and reconstruction techniques can be reliably compared. © American Roentgen Ray Society.

Clavet C.R.,Winchester Engineering and Analytical Center | Chaput M.P.,Winchester Engineering and Analytical Center | Silverman M.D.,Winchester Engineering and Analytical Center | Striplin M.,Winchester Engineering and Analytical Center | And 4 more authors.
Eye and Contact Lens | Year: 2012

OBJECTIVE:: To investigate the effects of eight different soft contact lenses on disinfection efficacy of a multipurpose solution (MPS) containing polyhexamethylene biguanide (PHMB) against Fusarium solani. METHODS:: Six silicone hydrogel lenses (galyfilcon A, senofilcon A, comfilcon A, enfilcon A, balafilcon A, and lotrifilcon B) and two conventional hydrogel lenses (polymacon and etafilcon A) were placed in polypropylene lens cases filled with MPS containing 0.0001% PHMB and soaked for 6, 12, 24, 72, and 168 hours. After each interval, depleted MPS from lens cases were removed and assayed for activity against F. solani according to International Organization for Standardization (ISO) 14729 stand-alone procedure. A portion was aliquoted for chemical analysis. RESULTS:: Soaking etafilcon A, balafilcon A, and polymacon lenses for 6 hours reduced the concentration of PHMB in MPS by more than half the stated labeled concentration, with concentrations below the limit of detection for etafilcon A-depleted and balafilcon A-depleted solutions after 12 and 72 hours of soaking, respectively. Except for comfilcon A-depleted solutions, all others failed to consistently obtain one log reduction of F. solani. The solutions soaked with etafilcon A, balafilcon A, and polymacon lenses for 24 hours or more lost all or almost all fungicidal activity against F. solani. CONCLUSIONS:: Over time, the disinfectant uptake by some lenses can significantly reduce the PHMB concentration and the fungicidal activity of the MPS against F. solani. Current ISO methodology does not address the reduction in microbiocidal efficacy when lenses are soaked in MPS. The ISO committee should consider adding "soaking experiments" to quantify the effect that contact lens materials have on the performance of MPSs. © 2012 Lippincott Williams & Wilkins.

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