Biological Molecular Imaging Section
The Biological Molecular Imaging Section focuses on identification of disease-specific biomarkers; development of new molecular imaging probes with cellular and molecular biology oriented techniques and methods; application of the developed probes into multimodality imaging; and collaborates with the other two LOMIN sections to characterize novel imaging or therapeutic agents, both in vitro and in vivo.
- Target Identification and Probe Development
Molecular imaging allows detection of specific targets in vivo, including visualization of the presence of targets, as well as the quantification of their spatial and temporal distribution. A target may be a single key protein or a particular pathway related to certain pathological processes. Our lab develops probes of small organic molecules, polypeptides, proteins, antibodies or aptamers by phage peptide display library screening, single chain antibody library screening, and systematic evolution of ligands by exponential enrichment (SELEX). The newly developed probes are then modified and optimized for in vivo molecular imaging application.
- Protein Engineering and Site-specific Labeling
Fluorophores, isotopes, and other detectable labels are most commonly introduced into a protein through in vitro modifications with suitable amine or thiol reactive reagents. Non-specific labeling of protein probes will cause heterogeneity and inaccuracy of quantification in the imaging process. Our lab engineers protein probes to accomplish site-specific modification. For example, with a system utilizing an mRNA template with an amber codon (UAG), instead of a normal initiating codon (AUG) and a complementary misaminoacylated initiator suppressor tRNA capable of initiating protein synthesis from the UAG codon, an artificial amino acid can be introduced into the N-terminal of synthesized proteins. Enzymatic post-translational modification of proteins utilizing inteins-mediated protein splicing is an alternative approach for site-specific labeling.
- Therapeutic Response Monitoring
Therapeutic efficacy is a key question that needs to be answered for ever drug or drug candidate. Molecular imaging is able to provide information to evaluate pharmacological effects. For instance, solid tumors are often characterized by having high glucose utilization, tumor cell proliferation, hypoxia with sustained angiogenesis and evasion of apoptosis. The influence of compounds targeting these characteristics of cancer biology can be selectively visualized by molecular imaging techniques. Examples include FDG PET to image glucose transport and metabolism, and FLT PET to evaluate the proliferating status. Additionally, some imaging strategies can focus on one particular pathway such as apoptosis and hypoxia or a single molecular target to access specific drugs.
- Reporter Gene Based Imaging
As a unique branch of molecular imaging, various reporter genes have been developed, and expression of reporter genes can be evaluated by multiple imaging modalities, including optical imaging, SPECT/PET or MRI. With split reporter gene or bioluminescence resonance energy transfer (BRET) system, protein-protein interactions can be visualized in living organisms. Our lab develops and applies reporter gene imaging to corroborate probe-based non-invasive imaging.
The Biological Molecular Imaging Section is physically located in building 9 and building 10, room B3B25.
The laboratory is equipped with instruments to perform cell biology and molecular biology experiments, such as cell culture, western blot, PCR, and gene and protein engineering. A Zeiss Axio Imager A2 LED upright bright field microscope is equipped for tissue staining and histological observation. An Olympus X-81 epifluorescent microscope and an Olympus Fluoview F10i-LIV fully automated confocal laser-scanning microscope allow us to investigate fluorophores label probes in tissue section or live cells. The surgery and imaging room 10/B3B25 is equipped with a cryomicrotome, a storage phosphor system, gamma counters, and liquid scintillation counters for ex vivo investigation.
The lab is also equipped with a stereotaxic mounted cortical impactor, a surgical microscope, a rodent ventilator and a body temperature controller for animal model establishment including traumatic brain injury (TBI), myocardial infarction (MI), hindlimb ischemia and various orthotopic tumor inoculation.
For live animal imaging, we are equipped with a Siemens Inveon PET/CT docking system to explore radiolabeled tracers, a CRI Maestro II for fluorescence imaging, and an IVIS Lumina II for both bioluminescence imaging and fluorescence imaging. We also get access to the NIH/MIF (Mouse Imaging Facility) to perform MRI imaging. Recently, we have installed a Vevo 2100 high frequency ultrasound system with integrated Vevo LAZR for ultrasound and photoacoustic (PA) imaging.
- PET of glucagonlike peptide receptor upregulation after myocardial ischemia or reperfusion injury. Gao H, Kiesewetter DO, Zhang X, Huang X, Guo N, Lang L, Hida N, Wang H, Wang H, Cao F, Niu G, Chen X. J Nucl Med. 2012 Dec.
- A nanoscale graphene oxide-peptide biosensor for real-time specific biomarker detection on the cell surface. Wang Z, Huang P, Bhirde A, Jin A, Ma Y, Niu G, Neamati N, Chen X. Chem Commun (Camb). 2012 Oct 9.
- Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe. Zhu L, Guo N, Li Q, Ma Y, Jacboson O, Lee S, Choi HS, Mansfield JR, Niu G, Chen X. Theranostics. 2012.
- Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging. Wang H, Gao H, Guo N, Niu G, Ma Y, Kiesewetter DO, Chen X. Theranostics. 2012.
- Molecular targeting of CEACAM6 using antibody probes of different sizes. Niu G, Murad YM, Gao H, Hu S, Guo N, Jacobson O, Nguyen TD, Zhang J, Chen X. J Control Release. 2012 Jul 10.
- Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles. Zhang F, Huang X, Zhu L, Guo N, Niu G, Swierczewska M, Lee S, Xu H, Wang AY, Mohamedali KA, Rosenblum MG, Lu G, Chen X. Biomaterials. 2012 Jul.
- Longitudinal PET imaging of doxorubicin-induced cell death with 18F-Annexin V. Hu S, Kiesewetter DO, Zhu L, Guo N, Gao H, Liu G, Hida N, Lang L, Niu G, Chen X. Mol Imaging Biol. 2012 Dec.
- PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2. Gao H, Lang L, Guo N, Cao F, Quan Q, Hu S, Kiesewetter DO, Niu G, Chen X. Eur J Nucl Med Mol Imaging. 2012 Apr.
- PET imaging of EGF receptors using [18F]FBEM-EGF in a head and neck squamous cell carcinoma model. Li W, Niu G, Lang L, Guo N, Ma Y, Kiesewetter DO, Backer JM, Shen B, Chen X. Eur J Nucl Med Mol Imaging. 2012 Feb.
- Imaging tumor-induced sentinel lymph node lymphangiogenesis with LyP-1 peptide. Zhang F, Niu G, Lin X, Jacobson O, Ma Y, Eden HS, He Y, Lu G, Chen X. Amino Acids. 2012 Jun.
- Imaging tumor endothelial marker 8 using an 18F-labeled peptide. Quan Q, Yang M, Gao H, Zhu L, Lin X, Guo N, Zhang G, Eden HS, Niu G, Chen X. Eur J Nucl Med Mol Imaging. 2011 Oct.
- PET of insulinoma using ¹⁸F-FBEM-EM3106B, a new GLP-1 analogue. Gao H, Niu G, Yang M, Quan Q, Ma Y, Murage EN, Ahn JM, Kiesewetter DO, Chen X. Mol Pharm. 2011 Oct 3.
- Multimodality imaging of tumor response to doxil. Zhang F, Zhu L, Liu G, Hida N, Lu G, Eden HS, Niu G, Chen X. Theranostics. 2011.
- PET imaging of early response to the tyrosine kinase inhibitor ZD4190. Yang M, Gao H, Yan Y, Sun X, Chen K, Quan Q, Lang L, Kiesewetter D, Niu G, Chen X. Eur J Nucl Med Mol Imaging. 2011 Jul.
- Multiplexed PET probes for imaging breast cancer early response to VEGF₁₂₁/rGel treatment. Yang M, Gao H, Sun X, Yan Y, Quan Q, Zhang W, Mohamedali KA, Rosenblum MG, Niu G, Chen X. Mol Pharm. 2011 Apr 4.
- 18F-FPPRGD2 and 18F-FDG PET of response to Abraxane therapy. Sun X, Yan Y, Liu S, Cao Q, Yang M, Neamati N, Shen B, Niu G, Chen X. J Nucl Med. 2011 Jan.
- Apoptosis imaging: beyond annexin V. Niu G, Chen X. J Nucl Med. 2010 Nov.
- Phage display-derived peptides for osteosarcoma imaging. Sun X, Niu G, Yan Y, Yang M, Chen K, Ma Y, Chan N, Shen B, Chen X. Clin Cancer Res. 2010 Aug 15.
- Cetuximab-based immunotherapy and radioimmunotherapy of head and neck squamous cell carcinoma. Niu G, Sun X, Cao Q, Courter D, Koong A, Le QT, Gambhir SS, Chen X. Clin Cancer Res. 2010 Apr 1.