A5011134643- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
- Medical Imaging and Pathology Studies
- Lung Cancer Research Studies
- Enzyme function and inhibition
- Radiation Therapy and Dosimetry
- Prostate Cancer Treatment and Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Glutathione Transferases and Polymorphisms
- bioluminescence and chemiluminescence research
- Nanoparticle-Based Drug Delivery
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Nanoplatforms for cancer theranostics
- Redox biology and oxidative stress
- Cell Adhesion Molecules Research
- Cutaneous Melanoma Detection and Management
- Cancer, Stress, Anesthesia, and Immune Response
- Insect and Pesticide Research
University of Iowa Hospitals and Clinics
2023-2024
Viewpoint Molecular Targeting (United States)
2021-2023
University of Iowa
2006-2023
University of Missouri
2009-2020
Harry S. Truman Memorial Veterans' Hospital
2009-2015
203Pb and 212Pb have emerged as promising theranostic isotopes for image-guided α-particle radionuclide therapy cancers. Here, we report a cyclen-based Pb specific chelator (PSC) that is conjugated to tyr3-octreotide via PEG2 linker (PSC-PEG-T) targeting somatostatin receptor subtype 2 (SSTR2). PSC-PEG-T could be labeled efficiently purified at 25 °C also 212Bi 80 °C. Efficient radiolabeling of mixed in was observed Post radiolabeling, stable Pb(II) Bi(III) radiometal complexes saline were...
Abstract Purpose The lead-203 ( 203 Pb)/lead-212 212 Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for cancer. Emerging evidence suggests that Pb-labeled peptide-based radiopharmaceuticals targeting somatostatin receptor subtype 2 (SSTR2) may provide improved effectiveness compared to beta-particle-based therapies neuroendocrine tumors (NETs). This study aims improve performance SSTR2-targeted imaging...
The 26 amino acid hemolytic melittin peptide was converted into a gene transfer that binds to DNA and polymerized through disulfide bond formation. Melittin analogues were synthesized by the addition of one four Lys repeats at either C- or N-subterminal end along with terminal Cys residues. able bind polymerize on plasmids resulting in formation condensates. In absence DNA, retained their red blood cell potency but inactive when bound plasmid DNA. vitro efficiency mediated poly-melittin...
Radiotherapy can facilitate the immune recognition of immunologically “cold” tumors and enhance efficacy anti-PD-1 anti-CTLA-4 checkpoint inhibitors (ICIs) in melanoma. Systemic administration receptor-targeted radionuclide therapy has potential to selectively deliver radionuclides multiple throughout body metastatic settings. By triggering immunologic cell death increasing susceptibility surviving tumor cells these locations, targeted therapies may overcome resistance ICIs render responsive...
Melanocortin 1 receptor (MC1R) is under investigation as a target for drug delivery metastatic melanoma therapy and imaging. The purpose of this study was to determine the potential using BRAF inhibitors (BRAFi) histone deacetylase (HDACi) enhance MC1R-targeted radiolabeled peptide ([212Pb]DOTA-MC1L) by pharmacologically upregulating MC1R expression in cells tumors. analyzed de-identified biopsies immunohistochemical staining. Upregulation determined BRAFV600E (A2058) wild-type (MEWO)...
Thioredoxin Reductase (TrxR) functions to recycle thioredoxin (Trx) during hydroperoxide metabolism mediated by peroxiredoxins and is currently being targeted using the FDA-approved anti-rheumatic drug, auranofin (AF), selectively sensitize cancer cells therapy. AF treatment decreased TrxR activity clonogenic survival in small cell lung (SCLC) lines (DMS273 DMS53) as well H727 atypical carcinoid line. also significantly sensitized DMS273 vitro sorafenib, an multi-kinase inhibitor that...
PEGylated glycoproteins (PGPs) were synthesized by copolymerizing a Cys-terminated PEG−peptide, glycopeptide, and melittin peptide. Compositionally unique PGPs prepared varying the ratio of PEG−peptide (20−90%) (0−70%) with constant amount glycopeptide (10%). The purified RP-HPLC, characterized for molecular weight polydispersity GPC-HPLC SDS-PAGE composition RP-HPLC following reduction to form monomeric peptides. formed DNA condensates 200−300 nm in diameter that administered mice via tail...
Intermediate to high-grade lung neuroendocrine tumors (NETs; i.e., atypical carcinoid tumors) and carcinomas (NECs) are currently difficult cure. These were found express the CXCR4 G-protein coupled receptor that can be targeted with radioligands. PCR flow cytometric analysis of NET NEC cell lines using an anti-CXCR4 antibody demonstrated all tested expressed CXCR4. PET/CT imaging 68Galium-pentixafor in mouse xenografts NETs NECs verified tumor targeting was blocked by a agonist. Clonogenic...
Analogues of the E. coli heat-stable enterotoxin (STh) are currently under study as both imaging and therapeutic agents for colorectal cancer. Studies have shown that guanylate cyclase C (GC-C) receptor is commonly expressed in cancers. It has also been STh peptides inhibit growth tumor cells expressing GC-C. The ability to determine GC-C status tissue using vivo molecular techniques would provide a useful tool optimization GC-C-targeted therapeutics. In this work, we compared binding...
This study describes the synthesis and preliminary biologic evaluation of an 111In-labeled peptide antagonist urokinase-type plasminogen activator receptor (uPAR) as a potential probe for assessing metastatic human breast cancer in vivo. The (NAc-dD-CHA-F-dS-dR-Y-L-W-S-βAla)2-K-K(DOTA)-NH2 was synthesized conjugated with DOTA chelating moiety via conventional solid-phase (SPPS), purified by reversed-phase HPLC, characterized MALDI-TOF MS binding assay. In vitro studies demonstrated IC50 240...
Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction proximal tubules, which may cause acute kidney injury (AKI) and chronic disease (CKD). Because tubular cells considered the primary site radiopeptides' renal injury, current use biomarkers glomerular functional loss limits evaluation possible nephrotoxicity its early detection....
Abstract We report the synthesis and evaluation of an enantiomerically enriched bifunctional chelator, ( S )‐ C ‐NE3TA. The chelator was efficiently prepared by regioselective stereoselective ring opening aziridinium ion. new chiral instantly almost completely bound to 64 Cu at room temperature. corresponding Cu‐radiolabeled complex remained intact in human serum for 48 h without any measurable transchelation tolerant a rigorous EDTA challenge 24 h. ‐NE3TA stable mice produced excellent...
Abstract Introduction/Background: Atypical lung carcinoids and neuroendocrine carcinomas (NECs) are currently incurable. Most of these cancers express the C-X-C chemokine receptor 4 (CXCR4), making CXCR4 an attractive target for cancer diagnosis treatment using radioligand therapy (RLT) with nuclides such as alpha emitter Pb212 conjugated to Pentixather (Pent). Alpha particles produce dense ionization tracks damage cytosolic structures mitochondria, leading generation reactive oxygen species...
ABSTRACT Introduction Small cell lung cancer (SCLC) has a 7% 5-year overall survival. C-X-C chemokine receptor 4 (CXCR4), an attractive target for theranostic agents, is highly expressed in SCLCs, and can be targeted with pentixather using the pair 212 Pb/ 203 Pb. The hypothesis that [ Pb]-pentixather used safely effectively imaging therapy SCLC xenograft models was tested. Results SPECT/CT biodistribution studies of tumor bearing mice injected demonstrated CXCR4-dependent uptake tumors...