Chemistry and Radiochemistry Section

The Chemistry and Radiochemistry Section (CRS) is part of the Laboratory of Molecular Imaging and Nanomedicine (LOMIN), NIBIB. The CRS furthers LOMIN’s multidisciplinary efforts to develop chemical entities and biological procedures to diagnose and treat human diseases. The CRS does this by development of: 1) chemical syntheses that create robust, selective entities to carry radionuclides and fluorophores for diagnostic imaging, 2) conjugation procedures that allow targeted delivery and specific release of therapeutic drugs, and 3) activatable probes with sensitivity to an in vivo parameter, such as pH, temperature, NO concentration, etc.

Chemical synthesis scheme

The Section develops novel radiolabeling methodologies, and exploits accepted ones, to prepare radiolabeled compounds for diagnostic and therapeutic applications. The PET isotopes, Ga-68, F-18, Cu-64, Zr-89, are matched, based on expected biological half-life, and applied to radiolabeling of small molecules, peptides, antibodies, aptamers, and nanomaterials. Small molecules are selected for specificity to an appropriate receptor and their synthesis (including synthesis of appropriate radiolabeling precursors) is conducted by chemical means. Peptides are designed with consideration of selectivity of radiolabel incorporation and specificity for the intended target. Antibodies and aptamers are preselected and appropriately prepared for radiolabeling procedures. Tumor radiation therapy studies use high energy beta-emitters such as Lu-177 and Y-90.

Activatable Probes
Image of a chemical structure of a fluroescent probe

Molecules that change their properties, (e.g., fluorescence emission, or nuclear relaxation), when acted upon by an enzyme, or in the presence of a change in pH or temperature, etc., are called activatable probes. Peptide probes can, for example, be designed by pairing a fluorophore with a black-hole-quencher; the resulting probes exhibit no fluorescence until an enzyme hydrolyzes a peptide bond causing an increase in distance between the fluorophore and quencher, thereby restoring fluorescence. We have used this to provide direct evidence of the presence of an MMP enzyme in cell culture.

Nano Constructs
Image of a gold silica nanorod

In collaboration with the Theranostic Nanomedicine Section, LOMIN we design nanomaterials that incorporate payloads such as chemotherapeutics, siRNA, etc. This is a subset of activatable probes. The goal is to activate the probes with a near infrared (NIR) laser to perform photodynamic therapy (PDT) or photothermal therapy (PTT), or to utilize some other unique feature of the pathogenic condition to cause release of the therapeutic payload. These projects involve development of unique chemical bonding methods, as well as novel nanoparticles, and serve as a strong links to the other sections of LOMIN.

The Chemistry and Radiochemistry Section works closely with the Biological Molecular Imaging Section and the Theranostic Nanomedicine Section of LOMIN and with the Molecular Tracer and Imaging Core Facility. LOMIN has four chemical fume hoods in Building 35A that are available to the three sections. There are an additional two located in the Core Facility in Building 10. The section has access to the radiochemical facilities of the Core Facility. The section has access to high performance liquid chromatography, gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy for compound identification and purity measurements. Equipment for particle size analysis, fluorescence spectroscopy, and molecular imaging are available in other sections of LOMIN or within the Core Facility.

Liu YWang GZhang HMa YLang LJacobson OKiesewetter DOZhu LGao SMa QChen X
Bioconjug. Chem.
2016 Jan 20

Liu ZChen HChen KShao YKiesewetter DONiu GChen X
Sci Adv
2015 Sep

Yue XWang ZZhu LWang YQian CMa YKiesewetter DONiu GChen X
Mol. Pharm.
2014 Nov 03

Zhu LMa YKiesewetter DOWang YLang LLee SNiu GChen X
ACS Chem. Biol.
2014 Feb 21