Annual report: EB000087-01 This core facility was established this year within the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The major theme of our work is to utilize radionuclides for diagnostic and therapeutic purposes. We have capabilities in synthesis and evaluation of optical imaging probes. The laboratory is well equipped with analytical chemistry equipment to allow identity and purity analyses to be conducted on entities ranging from small molecules to large proteins. This equipment includes high resolution liquid chromatography-mass spectrometry that can allow determination of the number of chelates on an antibody. We also house PET/CT and optical imaging devices in our laboratory. The majority of our work has been conducted as collaboration with the group of Dr. Xiaoyuan Chen, senior investigator, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), NIBIB. We have projects with other investigators from outside of NIBIB, but these represented a small portion of our time. The projects with LOMIN are highly collaborative; we provide chemistry and radiochemistry services for the projects; the radionuclide image acquisition and image processing is a joint effort with the core personnel serving as trainer and/or mentor, in some cases. Data interpretation and manuscript preparation are joint efforts among LOMIN and CORE members. 1) One project conducted in collaboration with Dr. Shawn Chen is the application of albumin binding molecules, conjugated to drug molecules, peptides, or other targeting molecules, to enhance the blood half-life and, hence, bioavailability of the targeting entity. An Evans blue analog was developed in LOMIN and has been evaluated extensively for improving image contrast for diagnostic purposes and for enhancing radiotherapeutic efficacy. For this project, CORE personnel developed an Evans blue-based moiety that contained a chelator for incorporation of radiometals and a maleimide for conjugating targeting molecules containing a free thiol. Successful diagnostic imaging and radiotherapy have been conducted in mouse xenograft models using target peptides for somatostatin and integrin receptors. a. We have discussed collaborations with NIDDK and NICHD to compare somatostatin ligands in additional tumor models. We expect to conduct studies on these projects during this fiscal year. 2) Radiolabeling antibody-drug-conjugates with radiometals has also been a component of our research portfolio. The pharmacokinetics and the in vivo internalization have been studied using both in vivo imaging and in vitro radioactivity counting. 3) Another goal of our LOMIN collaborator is the development of novel nanomaterials. We contributed to this project by assisting in the development of radiolabeling methods for the various particles under investigation in LOMIN. PET imaging of the radiolabeled nanomaterials provides information on the pharmacokinetics and biodistribution of these novel nanoparticles. LOMIN personnel can use this information to modify the nanoparticle design to achieve more desirable targeting or improved pharmacokinetics. 4) We have contributed to the development of fluorescently labeled molecules. In particular, peptides with a known enzymatic cleavage site were synthesized containing a fluorophore on one side of the cleavage site and a quencher on the other side. When these molecules are administered to a biological system, fluorescence will only be observed only after the enzyme cleaves the peptide linker. These molecules are used to probe for active enzyme in tumor xenograft models. 5) We have a mass spectrometry laboratory with two high resolution HPLC-MS systems. One of the instruments is almost exclusively used to conduct characterization of chemicals synthesized in LOMIN or by Core Facility personnel. The second, which promises higher mass resolution, is being evaluated to conduct studies of binding interactions between albumin and chemically synthesized binding molecules. We have begun conducting studies with investigators from other components of the NIH. Investigators from NIEHS, NIDDK, NICHD have contacted us for radiochemistry and / or imaging assistance with their projects. Some of these collaborations have developed because of previous LOMIN interactions. These projects are in a very early in design and development; little data has been acquired. We expect these external collaborations to be an on-going component of our work.
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