A5050421121- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Chemical Synthesis and Analysis
- Immunotherapy and Immune Responses
- Medical Imaging Techniques and Applications
- Cancer Research and Treatments
- Click Chemistry and Applications
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Viral Infections and Immunology Research
- Caveolin-1 and cellular processes
- Animal Disease Management and Epidemiology
- Nanoplatforms for cancer theranostics
- Signaling Pathways in Disease
- Amino Acid Enzymes and Metabolism
- Diet and metabolism studies
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
- 3D Printing in Biomedical Research
- S100 Proteins and Annexins
- Cellular Mechanics and Interactions
University of California, Davis
2015-2025
Palmetto Hematology Oncology
2007-2019
University of California Davis Medical Center
2007-2018
Maryland Oncology Hematology
2016
University of California System
2014
Mallinckrodt (United States)
2009
UC Davis Comprehensive Cancer Center
2007
West Health
2006
Guy's Hospital
1999
King's College London
1999
Abstract Arginine deprivation as an anticancer therapy has historically been met with limited success. The development of pegylated arginine deiminase (ADI-PEG20) renewed interest in for the treatment some cancers. efficacy ADI-PEG20 is directly correlated argininosuccinate synthetase (ASS) deficiency. CWR22Rv1 prostate cancer cells do not express ASS, rate-limiting enzyme synthesis, and are susceptible to vitro. Interestingly, apoptosis by 0.3 μg/mL occurs 96 hours posttreatment caspase...
Abstract Many cancers appear to activate intrinsic antioxidant systems as a means counteract oxidative stress. Some cancers, such clear cell renal carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed metabolism, at least in part due the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species other oxidants. We show here ccRCC xenograft tumors under capsule enhanced stress compared with adjacent normal tissue...
Abstract Expression of the epithelial-specific integrin αvβ6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation up-regulated dramatically by many different carcinomas, making a promising target for vivo detection cancer using noninvasive imaging. In addition, recognized as promoting invasion correlates with aggressive behavior human cancers thus agents that recognize specifically will an essential tool future management αvβ6-positive...
Abstract The cell surface receptor αvβ6 is epithelial specific, and its expression tightly regulated; it low or undetectable in adult tissues but has been shown to be increased many different cancers, including pancreatic, cervical, lung, colon cancers. Studies have described as a prognostic biomarker linked poor survival. We recently the feasibility of imaging vivo by positron emission tomography (PET) using peptide [18F]FBA-A20FMDV2. Here, we describe improved agents test their efficacy...
The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging a diverse range malignancies with PET.The αvβ6-BP prepared on solid phase radiolabeled 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, cell binding studies using paired αvβ6-expressing αvβ6-null lines. vivo evaluation (PET/CT, biodistribution, autoradiography) performed in mouse model bearing same xenografts. A first-in-human PET/CT...
Abstract Cells may be captured and released using a photodegradable hydrogel (photogel) functionalized with antibodies. Photogel substrates were used to first isolate human CD4 or CD8 T‐cells from heterogeneous cell suspension then release desired cells groups of by UV‐induced photodegradation. Flow cytometry analysis the retrieved revealed approximately 95 % purity T‐cells, suggesting that this substrate had excellent specificity. To demonstrate possibility sorting according their function,...
Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances a growing appreciation of the need for reliable, sensitive biomarkers human function health disease. Over last 30 years, large amount physics engineering effort PET has been motivated dominant application during that period, oncology. This led to developments such as PET/CT, whole-body PET, 3D accelerated statistical image reconstruction,...
Numerous radiolabeled peptides have been utilized for in vivo imaging of a variety cell surface receptors. For applications PET using [(18)F]fluorine, are via prosthetic group approach. We previously developed solution-phase (18)F-"click" radiolabeling and solid-phase 4-[(18)F]fluorobenzoic 2-[(18)F]fluoropropionic acids. Here we compare the three different approaches report effects on pharmacokinetics. The groups did an effect; metabolites with significantly polarities were observed.
Although T cells can be labeled for noninvasive in vivo imaging, little is known about the impact of such labeling on T-cell function, and most imaging methods do not provide holistic information trafficking kinetics, homing sites, or quantification. <b>Methods:</b> We developed protocols that minimize inhibitory effects <sup>64</sup>Cu-pyruvaldehyde-bis(<i>N</i>4-methylthiosemicarbazone) (<sup>64</sup>Cu-PTSM) function permit patterns to followed by PET. Thus, we ovalbumin (OVA) receptor...
Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide–drug conjugates (PDCs) that target tumor-specific receptors such as integrin αvβ6 are emerging powerful tools to overcome these challenges. The development of an αvβ6-selective PDC was achieved by combining the therapeutic efficacy cytotoxic drug monomethyl auristatin E with selectivity αvβ6-binding peptide (αvβ6-BP) and ability positron emission tomography (PET) imaging copper-64....
Abstract Despite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen‐related cell adhesion molecule (CEACAM)6 has been reported as potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 target, using an antibody–drug conjugate (ADC). Expression in adenocarcinomas was determined immunohistochemistry on tissue microarrays. The expression pattern granulocytes granulocytic...
The rapid development and translation of targeted molecular imaging agents from bench to bedside is currently a slow process, with clear bottleneck between the discovery new compounds an appropriate agent. ability identify promising agents, as well failures, much earlier in process using high-throughput screening techniques could save significant time money. This work combines advantages combinatorial chemistry, site-specific solid-phase radiolabeling, vivo for agents. A...
Significant upregulation of the integrin α v β 6 has been described as a prognostic indicator in several cancers, making it an attractive target for tumor imaging. This study compares variants PEGylated -targeting peptide, bearing either [>18F]fluorobenzoyl prosthetic group ([ 18 F]FBA-PEG-A20FMDV2) or different [ 64 Cu]copper chelators (DOTA-PEG-A20FMDV2, CB-TE2A-PEG-A20FMDV2). The compounds were evaluated vitro by enzyme-linked immunosorbent assay (against and closely related ) cell...
The strain-promoted click 1,3-dipolar cycloaddition reactions involving azides and cyclooctynes for the synthesis of triazoles offer advantage being able to be performed in biological settings via copper-free chemistries. While strained reagents conjugated optical dyes radiometal conjugates have been reported, cyclooctyne labeled with fluorine-18 ((18)F) radiochemically evaluated a reaction yet explored. This report describes conversion bifunctional azadibenzocyclooctyne (ADIBO) amine...
Radiotracers based on the peptide A20FMDV2 selectively target cell surface receptor integrin α<sub>v</sub>β<sub>6</sub>. This has been identified as a prognostic indicator correlating with severity of disease for several challenging malignancies. In previous studies peptides labeled 4-<sup>18</sup>F-fluorobenzoic acid (<sup>18</sup>F-FBA), we have shown that introduction poly(ethylene glycol) (PEG) improves pharmacokinetics, including increased uptake in α<sub>v</sub>β<sub>6</sub>-expressing...
We have used noise-equivalent count (NEC) rates to optimize rate performance for 3D acquisition in PET a wide range of situations, with particular reference imaging the torso. also compared NEC 2D and order establish conditions under which mode offers an improvement over mode. Measurements were performed on four tissue-equivalent phantoms ranging size from that infant's head (13 cm diameter) obese adult's chest 37 by 48 cm. Count data acquired as function phantom size, activity field view,...