- Medical Imaging Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Radiopharmaceutical Chemistry and Applications
- Virus-based gene therapy research
- Nanoplatforms for cancer theranostics
- Nanoparticle-Based Drug Delivery
- Cancer, Hypoxia, and Metabolism
- Quantum Dots Synthesis And Properties
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Advanced Nanomaterials in Catalysis
- bioluminescence and chemiluminescence research
- Advanced Radiotherapy Techniques
- Nitric Oxide and Endothelin Effects
- Lanthanide and Transition Metal Complexes
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Glioma Diagnosis and Treatment
- Nanocluster Synthesis and Applications
- HER2/EGFR in Cancer Research
- Herpesvirus Infections and Treatments
- Photodynamic Therapy Research Studies
- Carbon and Quantum Dots Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiomyopathy and Myosin Studies
Virginia Commonwealth University
2012-2023
University Health System
2023
University of Richmond
2014-2016
University of California, Los Angeles
2002-2013
Institute for Molecular Medicine
2001-2005
Stanford University
2003-2005
UCLA Jonsson Comprehensive Cancer Center
2002
The current method of analyzing myocardial cell transplantation relies on postmortem histology. We sought to demonstrate the feasibility monitoring transplanted survival in living animals using molecular imaging techniques.For optical bioluminescence charged-coupled device imaging, rats (n=20) underwent intramyocardial injection embryonic rat H9c2 cardiomyoblasts (3x10(6) 5x10(5)) expressing firefly luciferase (Fluc) reporter gene. Cardiac signals were present for more than 2 weeks with...
The ability to monitor reporter gene expression noninvasively offers significant advantages over current techniques such as postmortem tissue staining or enzyme activity assays. Here we demon-strate a novel method of repetitively tracking in vivo firefly luciferase (FL) skeletal muscles mice using cooled charged coupled device (CCD) camera. We first show that the CCD camera provides consistent and reproducible results within ±8% standard deviation from mean values, detection sensitivity...
Abstract Antibody fragments are recognized as promising vehicles for delivery of imaging and therapeutic agents to tumor sites in vivo. The serum persistence IgG1 with intact Fc region is controlled by the protective neonatal receptor (FcRn) receptor. To modulate half-life engineered antibodies, we have mutated Fc-FcRn binding site chimeric anti–carcinoembryonic antigen (CEA) antibodies produced a single-chain Fv-Fc format. anti-CEA T84.66 format wild-type five mutants (I253A, H310A, H435Q,...
Background — Imaging reporter gene expression is useful for noninvasive monitoring of therapy. In this study, we imaged cardiac in living rats using micro positron emission tomography (microPET). Methods and Results Rats (n=10) underwent intramyocardial injection with 1×10 9 pfu adenovirus carrying cytomegalovirus promoter-driving herpes simplex virus type 1 mutant thymidine kinase (Ad-CMV-HSV1-sr39tk) as PET gene. Control (n=4) received firefly luciferase (Ad-CMV-Fluc). On days 2 to 4,...
Abstract We have recently described the in vivo properties of an iodinated anti-p185HER2 engineered antibody fragment [minibody (scFv-CH3)2; 80 kDa], made from internalizing 10H8 monoclonal antibody. Although minibody showed excellent binding to target vitro, only modest tumor uptake [5.6 ± 1.7% injected dose per gram (ID/g) tissue] was achieved nude mice bearing MCF7/HER2 breast cancer tumors. Here, attempt improve targeting, conjugated 1,4,7,10-tetraazacyclododecane-N, N′, N′′,...
Background — Studies of cardiac gene transfer rely on postmortem analysis using histologic staining or enzyme assays. Noninvasive imaging the temporal and spatial characteristics expression in same subject offers significant advantages. Methods Results Rats underwent direct myocardial injection via left thoracotomy with adenovirus-expressing firefly luciferase (Ad-CMV-Fluc; n=30). The reporter substrate d -luciferin was injected intraperitoneally. Serial images were acquired by use a cooled...
Abstract Purpose: Insulin-like growth factor-I receptor and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways are among the most active areas drug discovery in cancer research. However, due to their integral roles insulin signaling, inhibitors targeting these often lead hyperglycemia hyperinsulinemia. We investigated mechanism induced by GSK690693, a pan-AKT kinase inhibitor clinical development, as well methods ameliorate side effects. Experimental Design: The effect...
An engineered anti‐carcinoembryonic antigen (CEA) diabody (scFv dimer, 55 kDa) was previously constructed from the murine anti‐CEA T84.66 antibody. Tumor targeting, imaging and biodistribution studies in nude mice bearing LS174T xenografts with radiolabeled demonstrated rapid tumor uptake fast blood clearance, which are favorable properties for an agent. Current radiolabeling approaches result random modification of protein surface, may impair immunoreactivity especially smaller antibody...
Background— This study examines the quantitative accuracy, detection sensitivity, and time course of imaging expression a mutant herpes simplex type-1 virus thymidine kinase (HSV1-sr39tk) PET reporter gene in rat myocardium by using probe 9-(4-[ 18 F]-Fluoro-3-Hydroxymethylbutyl)-Guanine ([ F]-FHBG) small-animal (microPET). Methods Results— In 40 rats, adenovirus expressing HSV1-sr39tk driven cytomegalovirus promoter (Ad-CMV-HSV1-sr39tk, 1×10 6 to 9 pfu) was injected through thoracotomy...
Abstract Here, evidence suggests that nitric oxide synthases (NOS) of tumor cells, in contrast with normal tissues, synthesize predominantly superoxide and peroxynitrite. Based on high-performance liquid chromatography analysis, the underlying mechanism for this uncoupling is a reduced tetrahydrobiopterin:dihydrobiopterin ratio (BH4:BH2) found breast, colorectal, epidermoid, head neck tumors compared tissues. Increasing BH4:BH2 reconstitution coupled NOS activity breast cancer cells BH4...
We have previously validated the use of micro-positron emission tomography (microPET) for monitoring expression a single PET reporter gene in rat myocardium. now report bicistronic adenoviral vector (Ad-CMV-D2R80a-IRES-HSV1-sr39tk) linking 2 genes, mutant dopamine type receptor (D2R80a) and herpes simplex virus 1 thymidine kinase (HSV1-sr39tk), with aid an internal ribosomal entry site (IRES).Rat H9c2 cardiomyoblasts transduced increasing titers Ad-CMV-D2R80a-IRES-HSV1-sr39tk (0 to 2.5x10(8)...
Primary ciliary dyskinesia (PCD), resulting from defects in cilia assembly or motility, is caused by mutations a number of genes encoding axonemal proteins. PCD phenotypes are variable, and include recurrent respiratory tract infections, bronchiectasis, hydrocephaly, situs inversus, male infertility. We generated knockout mice for the sperm-associated antigen-17 (Spag17) gene, which encodes central pair (CP) protein present axonemes cells with "9 + 2" motile flagella. The targeting Spag17...
Cerium oxide nanoparticles (CONPs) have demonstrated protection properties against oxidation in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction CONPs with biological compartments 'in situ' crucial to understand their biochemical physiological vivo. In this paper, a multifunctional nanoparticle platform was obtained through an intrinsic radiolabeling strategy extrinsic surface functionalization combine dual imaging components (Single...
The overall objective of this study is to non-invasively image and assess tumor targeting retention directly labeled T-lymphocytes following their adoptive transfer in mice. obtained from draining lymph nodes 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, grown the presence Interleukin-2 6 days. then 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels cell...
Radiolabeled liposomes have been employed as diagnostic tools to monitor in vivo distribution of real-time, which helps optimizing the therapeutic efficacy liposomal drug delivery. This work utilizes platform [111In]-Liposome a delivery vehicle, encapsulating novel 18F-labeled carboplatin derivative ([18F]-FCP) dual-molecular imaging tool both radiolabeled and carrier. The approach has potential for clinical translation individual patients using dual modal clinically-relevant radionuclides...
Height is the result of many growth and development processes. Most genes associated with height are known to play a role in skeletal development. Single-nucleotide polymorphisms SPAG17 gene have been human height. However, it not clear how this influences linear growth. Here we show that targeted mutation Spag17 leads malformations. Hind limb length mutants was significantly shorter than wild-type mice. Studies revealed differences maturation femur tibia suggesting alterations patterning....
A highly stable bimodal indium(111) radiolabeled indium QDs were synthesized for <italic>in vivo</italic> SPECT/fluorescence imaging.
Alginate microbeads incorporating adipose-derived stem cells (ASCs) have potential for delivering viable capable of facilitating tissue regeneration. These are formed in calcium crosslinking solutions containing organic osmolytes to ensure physiological osmolality, but the comparative effects these on microencapsulated not known. In addition, delivery parameters needed use regeneration remain unknown. We investigated following parameters: (1) osmolyte microbead diameter, cell viability and...
Astrocyte elevated gene-1 (AEG-1), also known as MTDH (metadherin) or LYRIC, is an established oncogene. However, the physiological function of AEG-1 not known. To address this question, we generated knock-out mouse (AEG-1KO) and characterized it. Although AEG-1KO mice were viable fertile, they significantly leaner with prominently less body fat lived longer compared wild type (WT). When fed a high cholesterol diet (HFD), WT rapidly gained weight, whereas did gain weight at all. This...