A5085127146- Cancer Immunotherapy and Biomarkers
- Medical Imaging Techniques and Applications
- Lung Cancer Treatments and Mutations
- Radiopharmaceutical Chemistry and Applications
- Photodynamic Therapy Research Studies
- Drug Transport and Resistance Mechanisms
- Fluorine in Organic Chemistry
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Neonatal Health and Biochemistry
- Chronic Lymphocytic Leukemia Research
- Click Chemistry and Applications
- Pharmacological Effects and Toxicity Studies
- Porphyrin and Phthalocyanine Chemistry
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Glioma Diagnosis and Treatment
- Organoselenium and organotellurium chemistry
- Synthesis and Catalytic Reactions
- Chemical Reactions and Isotopes
- Sphingolipid Metabolism and Signaling
- PI3K/AKT/mTOR signaling in cancer
- Sulfur-Based Synthesis Techniques
- Cancer Genomics and Diagnostics
- Pharmacogenetics and Drug Metabolism
Bristol-Myers Squibb (United States)
2014-2023
Bristol-Myers Squibb (Belgium)
2023
University of British Columbia
2013
University at Buffalo, State University of New York
2003-2008
University of Rochester Medical Center
2006-2008
Eli Lilly (United States)
2008
University of Michigan
2008
Abstract PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor expression might limit the predictive value small biopsies. Here we show that PD-1 can be quantified non-invasively using PET-CT in patients non-small-cell lung cancer. Whole body reveals significant tracer uptake heterogeneity both between patients, as well within different lesions.
The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status primary metastatic lesions could be important optimizing drug therapy. Herein, we have evaluated tumor targeting of an anti–PD-L1 adnectin after <sup>18</sup>F-fluorine labeling. <b>Methods:</b> An was labeled with <sup>18</sup>F 2 steps. This synthesis featured fluorination novel...
We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The provides access to broad range aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well unactivated that are typically inaccessible by due competing elimination. In addition, we show the decarboxylative conditions readily adapted radiofluorination with [18F]KF. propose reactions proceed two electron...
Photophysical properties of a series tetramethylrosamine dyes in which the xanthylium oxygen atom has been replaced with sulfur or selenium were examined. Dyes and, especially, show decreased fluorescence quantum yield and lifetimes, while at same time proportionally larger increases rates intersystem crossing lead to higher triplet yields (0.23 0.97, correspondingly). The selenium-containing dye (TMR−Se) displays prominent phosphorescence 77 K room temperature when solution is purged...
The first tellurium-containing analogues of the rosamine and rhodamine dyes were prepared by addition Grignard or organolithium reagents to telluroxanthone precursors. 125Te spectra both precursors are reported. One derivative was characterized X-ray crystallography found have a nearly planar telluroxanthylium core with 9-aryl substituent held orthogonal core. Density functional theory (DFT) time-dependent DFT (TDDFT) calculations performed analyze trends for excitation wavelengths observed...
Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was via a tandem trapping [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) synthesized followed by an intermolecular cycloaddition between [(11)C]isocyanate isothiocyanate form the 1,2,4-thiadiazolidine-3,5-dione...
Blocking the interaction of immune checkpoint molecule programmed cell death protein-1 and its ligand, PD-L1, using specific antibodies has been a major breakthrough for oncology. Whole-body PD-L1 expression PET imaging may potentially allow better prediction response to protein-1–targeted therapies. Imaging is feasible by with adnectin protein <sup>18</sup>F-BMS-986192. However, radiofluorination proteins such as BMS-986192 remains complex labeling yields are low. The goal this study was...
The electrophilic cyclization of N,N-diethyl 4-N,N-(dimethylamino)-2-(3-N,N-dimethyldimethylaminophenylchalcogeno)benzamides 7 with POCl3 and triethylamine in CH2Cl2 or acetonitrile gave excellent yields (77−97% CH2Cl2, 73−77% acetonitrile) the corresponding 2,7-bis-N,N-dimethylaminochalcogenoxanthen-9-ones 6. 3-Methoxyphenylchalcogo-substituted benzamide derivatives were much less reactive toward phenylchalcogeno-substituted no reaction after 48 h.
Chemoselective methionine bioconjugation with alkyne-bearing oxaziridine and iodonium salts was investigated as a new platform for site-selective radiolabeling of proteins peptides fluorine-18. Alkyne-bearing sulfimide conjugates, resulting from modification, underwent copper-assisted alkyne–azide cycloaddition (CuAAC) an 18F-labeled PEGylated azide to afford triazoles in excellent radiochemical yields. Diazoester sulfonium salt bioconjugates, formed 2-diazoiodonium salts, gave low yields...
The multidrug resistance efflux pump P-glycoprotein (Pgp) couples drug export to ATP binding and hydrolysis. Details regarding trajectory, as well the molecular basis for coupling, remain unknown. Nearly all drugs exported by Pgp have been assayed competitive behavior with rhodamine123 transport at a canonical "R" site. Tetramethylrosamine (TMR) displays relatively high affinity when compared other rhodamines. Here, we present construction characterization of library compounds based upon TMR...
The lysophosphatidic acid receptor type 1 (LPA1) is of 6 known receptors the extracellular signaling molecule acid. It mediates effects such as cell proliferation, migration, and differentiation. In lung, LPA1 involved in pathways leading, after lung tissue injury, to pulmonary fibrosis instead normal healing, by mediating fibroblast recruitment vascular leakage. Thus, a PET radiotracer may be useful for studying or developing LPA1-targeting drugs. We developed evaluated 11C-BMT-136088...
High throughput next-generation sequencing technology has enabled the collection of genome-wide sequence data and revolutionized single nucleotide polymorphism (SNP) discovery in a broad range species. When analyzed within population genomics framework, SNP-based genotypic may be used to investigate questions evolutionary, ecological, conservation significance natural populations non-model organisms. Kokanee salmon are recently diverged freshwater sockeye (Oncorhynchus nerka) that exhibit...
Positron emission tomography (PET) is an important non-invasive tool to help guide the drug discovery and development process. Positron-emitting–radiolabeled candidates represent for hunters gain insight into a drug's biodistribution target engagement of exploratory biologic targets interest. Recently, there have been several that incorporate acryloyl functional group due their ability form covalent bond within biological interest through Michael addition. Methods carbon-11 radionuclide...
The reaction of N, N-diethyl 4-(N', N'-dimethylamino)-2-phenylselenobenzamide (7a), 4-methoxy-2-phenylselenobenzamide (7b), N'-dimethylamino)-2-[(3-(N, N-dimethylamino)phenylseleno]benzamide (7c), and 4-methoxy-2-(3-methoxyphenylseleno)-benzamide (7d) with excess lithium diisopropylamide (LDA) gave 2-N, N-(dimethylamino)-9H-selenoxanthone (9a), 2-methoxy-9H-selenoxanthone (9b), 2,7-bis-N, (9c), 2,5-dimethoxy-9H-selenoxanthone (9d) in 70%, 59%, 23%, 90% isolated yields, respectively....
e20047 Background: Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD-(L)1 monotherapy in pts NSCLC. Aim: 1. To assess safety of the PET procedures. 2. quantify PD-1 and expression tumors 89 Zirconium-labeled nivolumab ( Zr-nivo) 18 F-labeled BMS-986192 F-PD-L1) PET. 3. intra- inter-patient tracer uptake differences tumors. 4. correlate results outcome. Methods: NSCLC eligible for were included. Pts received a dynamic static whole body F-PD-L1 Zr-nivo scan. A...
The multidrug efflux pump P-glycoprotein (Pgp) couples drug transport to ATP hydrolysis. Previously, using a synthetic library of tetramethylrosamine (TMR) analogues, we observed significant variation in ATPase stimulation (VmD). Concentrations required for half-maximal (KmD) correlated with hydrolysis transition-state stabilization and occlusion (EC50D) at single site. Herein, characterize several TMR analogues that elicit modest turnover (kcat ≤ 1–2 s−1) compared verapamil (VER) ∼ 10 s−1)....
Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and consequently been developed as positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [ 11 C]ibrutinib through C-carbonylation acrylamide functional group, by reaction secondary amine precursor with C]CO, iodoethylene, palladium–NiXantphos. C]Ibrutinib was reliably formulated radiochemical yields 5.4% ± 2.5% (non-decay...
<p>We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The provides access to broad range aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well unactivated that are typically inaccessible by due competing elimination. In addition, we show the decarboxylative conditions readily adapted radiofluorination with [<sup>18</sup>F]KF. We propose...