A5039604200- Radiopharmaceutical Chemistry and Applications
- Nanoparticle-Based Drug Delivery
- Medical Imaging Techniques and Applications
- Nanoplatforms for cancer theranostics
- Glioma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- Medical Imaging and Pathology Studies
- Chemical Synthesis and Analysis
- Radiomics and Machine Learning in Medical Imaging
- DNA and Nucleic Acid Chemistry
- Neuroendocrine Tumor Research Advances
- Neuroblastoma Research and Treatments
- Fluorine in Organic Chemistry
- Luminescence and Fluorescent Materials
- CAR-T cell therapy research
- Traumatic Brain Injury and Neurovascular Disturbances
- Virus-based gene therapy research
- Lanthanide and Transition Metal Complexes
Molecular Innovations (United States)
2016-2023
Cornell University
2015-2023
University of British Columbia
2002-2023
Weill Cornell Medicine
2016-2023
Howard Hughes Medical Institute
2010
University of California, San Diego
2010
TRIUMF
2005-2010
BC Cancer Agency
2010
University of British Columbia Hospital
2008
Abstract The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration multi‐ingredients. Herein, cytotoxic near‐infrared (NIR) dye (IR‐797) its nanoassembly are reported for multifunctional cancer theranostics. hydrophobic IR‐797 molecules self‐assembled into nanoparticles, which further modified with an amphiphilic polymer (C18PMH‐PEG5000) on surface. prepared PEG‐IR‐797 nanoparticles (PEG‐IR‐797 NPs) possess inherent...
Organometalloid compositions of silicon and boron permit rapid, high-yielding, one-step radiolabeling a covalently linked protein ligand (biotin) under aqueous conditions to give the corresponding alkyltetrafluorosilicates aryltrifluoroborate salts. Biotin was chosen as test for targeting because its quantitative interaction with avidin, which in turn allowed us calculate fluoridation yields that approach 80−100%. The silicate found be moderately stable hydrolysis, whereas borate appears so...
The use of a boronic ester as captor aqueous [(18)F]-fluoride has been previously suggested means labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [(18)F]-labeled trifluoroborate should humorally stable such that it neither leaches free bone nor accumulates therein. Herein, we have synthesized biotinylated is converted corresponding salt presence [(18)F]-fluoride. In keeping with its vitro kinetic stability at...
Whereas electron withdrawing substituents retard the rate of aryltrifluoroborate solvolysis, electron-donating groups enhance it. Herein is presented a Hammett analysis solvolytic lability aryltrifluoroborates where log(ksolv) values correlate to σ with ρ value approximately −1. This work provides predictable rubric for tuning reactivity boron several uses including 18F-labeled PET reagents and has mechanistic implications ArBF3-enhanced ligandless metal-mediated cross coupling reactions...
Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern activity. While useful, these data are 1-dimensional and lack spatiotemporal information related treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), PET, quantitatively longitudinally visualize whole-body distribution antitumor dynamics using clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing cells were...
We combine a novel boronate trap for F− with near-infrared fluorophore into single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and fluorescence (NIRF). Our first application of this generic tag is label Lymphoseek (tilmanocept), an agent designed receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates 18F− in single, aqueous step, targets mouse SLN rapidly (1 h) reduced distal accumulation, permits PET or...
Matrix metalloproteinases (MMP), strongly associated pathogenic markers of cancer, have undergone extensive drug development programs. Marimastat, a noncovalent MMP inhibitor, was conjugated with FITC to label cellular metalloproteinase cancer targets in MDA-MB-231 cells vitro. Punctate localization active transmembrane MMP14 observed. For molecular-targeted positron emission tomography imaging syngeneic 67NR murine mammary carcinoma vivo, marimastat (18)F-labeled using shelf-stable...
Abstract Organotrifluoroborates solvolyze in water at rates that vary over five orders of magnitude. The negative logarithm the solvolytic rate constant, p k (BF) , correlates exceptionally well with K a analogous carboxylic acid ( R 2 =0.984). This unforeseen correlation may be predictive value for several applications including Suzuki–Miyaura cross‐coupling reactions and design 18 F‐organotrifluoroborate radioprosthetic groups.
Site-specific RNA cleavage has received considerable attention over the years. Directed synthesis to append imidazoles or amines both oligonucleotides target specific represents an exciting avenue of research. However, date catalysis by such synthetic constructs, particularly in terms turnover, been difficult observe. This is first report a truly catalytic M2+-independent DNAzyme synthetically modified with and cationic that would seem mimic RNaseA. work now demonstrates how organic...
[18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 radiolabeled with a radiochemical yield that ≥27% and molar activity of 190 ± 50 mCi/μmol <1 h, one-step, aqueous isotopic exchange reaction. allows PSMA expression to be imaged by fluorescence (FL) [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 1.33 nM) cancers are specifically delineated mice bear 3 million (18 mg) PC3 (control, PSMA-negative) cells. Colocalization [18/19F]-4...
Abstract An effective tumoral delivery system should show minimal removal by the reticuloendothelial (RES), promote tumor uptake and penetration, minimize on‐site clearance. This study reports design synthesis of advanced self‐assembling peptide nanofiber precursor (NFP) analogues. The peptidic nature NFP offers flexibility for on‐demand customization with imaging agents surface charges while maintaining a set size, allowing real‐time monitoring kinetic dynamic multimodal...
Herein we report evidence for a light-inducible DNAzyme. In so doing, also disclose the synthesis and photochemical properties of novel nucleoside: 8-(2-(4-imidazolyl)ethyl-1-thio)-2'-deoxyriboadenosine (d1). The light sensitivity (d1) was evaluated via an examination photoinduced reactivation DNAzyme 8−17E from inactive form that contained single nucleotide modification. Restoration activity results reversion to unmodified deoxyadenosine. Deuterium studies indicate water is source hydrogen...
Inspired by recent interest in DNAzymes as transition metal ion sensors, a survey of the effects various metals on intramolecular cleavage rate an imidazole modified, M2+-independent, self-cleaving "925–11" DNA is reported. In particular, 925–11 activity was strongly inhibited Hg2+ (KdAPP = 110 ± 9 nM). It postulated that affinity and selectivity for stems from fact this synthetically modified DNAzyme contains imidazoles. This study demonstrates utility nucleotides developing sensors ions,...
Marimastat, a clinically trialed drug developed to treat breast cancer by inhibiting cancer-associated matrix metalloproteases (MMPs), was linked an aryl boronic ester for single-step [18F]-aqueous fluoride capture and the labeled product revealed tumor associated MMP activity in vivo. Herein, we report important radiosynthetic attributes labeling marimastat that enabled first PET images of syngenic murine model. The advantages this method include one-step post synthetic less than one hour...
The blood-brain barrier (BBB) represents a major obstacle in delivering therapeutics to brain lesions. Convection-enhanced delivery (CED), method that bypasses the BBB through direct, cannula-mediated drug delivery, is one solution maintaining increased, effective concentration at these CED was recently proven safe phase I clinical trial against diffuse intrinsic pontine glioma (DIPG), childhood cancer. Unfortunately, exact relationship between size, charge, and pharmacokinetic behavior...
A DNAzyme, synthetically modified with both primary amines and imidazoles, is found to act as a M2+-independent AP lyase-endonuclease. In the course of cleavage reaction, this DNAzyme forms covalent Schiff base intermediate an abasic site on complementary oligodeoxyribonucleotide. This intermediate, which inferred from NaCNBH3 trapping well cyanide inhibition, does not evidently accumulate because second step, dehydrophosphorylative elimination, fast compared formation. The 5'-product that...
New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached a biotin-bearing dioxaborolane, which facilitates antibody immobilization on streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled release from the solid phase, separated unlabeled antibody, creates [(18)F]-trifluoroborate-antibody for positron emission tomography near-infrared...
In vivo, real-time image-guided CED of a PET-imageable HDAC inhibitor is needed to improve survival in murine models DIPG.