Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D; community with critical information on the tools, technologies, and trends that drive the biotech industry.
Issue link: http://gen.epubxp.com/i/695748
Genetic Engineering & Biotechnology News | GENengnews.com | JULY 2016 | 31 tibody fragments (called minibodies and di- abodies) in a process coined immunoPET. She favors PET because it can, she says, be combined with the specifcity of antibodies. "One of the key features of antibodies is they have very long circulating half-lives," she points out. "Antibodies stay in the blood for days to weeks." To match the half-lives of antibodies, she and others have been testing longer-lived positron emitters, such as zirconi- um-89. "The fuorine-18 everyone uses has a two-hour half-life, so it's a challenge to make a fragment that targets and clears quickly enough to image." Zirconium-89, in contrast, has a half-life that is a little over three days. According to Dr. Wu, the use of PET brings certain caveats to mind. For exam- ple, you can only image one target at a time through this method, which is why she advo- cates multimodal approaches. PET can also be rather expensive. "But on the other hand," says Dr. Wu, newer cancer treatments, such as checkpoint inhibitors, can cost between $100,000 and $200,000 per year, "and they might be ineffective and very toxic." Her im- munoPET antibodies could be used to guide the use of expensive therapies. Dr. Wu's laboratory has published on roughly 8 to 10 cancer targets using this system. They have also begun to target im- mune cells using standard CD markers. "We started with CD8," recalls Dr. Wu. In 2015, in an article that appeared in the Journal of Nuclear Medicine, Dr. Wu and colleagues showed both CD4 and CD8 T cell recon- stitution in the bone marrow via PET. "You can watch the repopulation of either CD4 or CD8 compartments in the mouse," she de- tails, "and you can see the spleen and lymph nodes flling out over time." Dr. Wu hopes to see these techniques used in the tracking of immunological disease re- sponses. "When you talk about patient-op- timized treatments, you have to have a way of looking at the whole patient," she posits. "Our company is based on the belief that these kinds of very specifc imaging agents will be invaluable to that effort." Novel MRI Imaging Detectors A short way across town, Julia Ljubi- mova, M.D., Ph.D., director of the Nano- medicine Research Center, department of neurosurgery at Cedars-Sinai Medical Cen- ter, frmly believes that the future of imag- ing is in MRI. She has several multimillion dollar grants from the NIH and the NCI to develop MRI-detectable tumor biomarkers and therapeutics. Dr. Ljubimova and colleagues are work- ing on imaging technologies that incorporate nontoxic, biodegradable nanobioconjugates. These constructs are able to cross the blood- brain barrier (BBB) using receptor-mediated transcytosis. "Our nanoplatform," she ex- plains, "is a natural polymer that we obtain from a one-celled organism." The platform—which consists of a poly- malic acid scaffold, a target monoclonal antibody or peptides, and gadolinium en- hancement reagent—was designed by Ger- man chemist Eggehard Holler, Ph.D., now a professor in the same department as Ljubi- mova Dr. at Cedar-Sinai. "We developed this for MRI," explains Dr. Ljubimova, "because MRI is the method that is widely spread in almost every hospital." PET, she says, is more expensive, requires radionucleotides, and "requires clinical chemists that will synthe- size things 24 hours prior to the procedure." Her focus is on neurological disorders, neuro-oncology, and metastasizing cancers of the brain. "If you are thinking about us- ing a nanoplatform to image the brain," she points out, "you have to recognize, number one, that it has to go through the blood-brain barrier." It also has to be nontoxic and easily cleared from the system. Her nanoplatform, she claims, degrades into carbon dioxide and water within 12 hours. According to Dr. Ljubimova, current technologies are not as targeted as they should be. For example, brain imaging en- hancements can be caused by infammation, metastatic disease, primary brain tumors, or a combination of these factors. "Infam- mation you have to treat with antibiotics, metastatic disease you treat with one drug, and primary brain cancer you treat with an- other," she continues. Targeted imaging studies are very impor- tant for developing a strategy of treatment. "For brain, it would be easier to have a mo- lecular MRI diagnosis," she says. "It is not only brain problems we can solve," with their MRI approach, "but with breast (can- cer and others) it is easier to do a biopsy." "Our technology is very fexible," she in- sists, "We have a precise nanodrug that tar- gets pathological conditions in the brain. It's like a key in a locker. If the normal cell doesn't have the marker, then our drug doesn't go to this cell." Of note, these nanobioconjugates can be used for both imaging and therapy. For targeted therapy, the same scaffold can be used with a different chemical attached, one that is potentially deadly to the tumor. "My major interest always was molecular cancer biomarkers," states Dr. Ljubimova. "It would be revolutionary if MRI technol- ogy could not only give us a radiological sig- nal of enhancement in the brain or lung, but also be based on specifc molecular markers, which are constantly changing during the tumor progression and important for treat- ment modulation." Imaging Core Perhaps, however, the answer does not lie in either MRI imaging or PET, but in a combina- tion of technologies with a focus on improving patient outcomes. One place where advance- ment in imaging is apparent is within univer- sity core facilities. At the University of Notre Dame, 19 core facilities provide resources and instrument support for internal and external clients, part of a growing trend to provide ex- pensive technologies to more researchers. "We offer our services to the entire uni- versity," says Sarah Chapman, assistant di- rector of biological imaging and manager of the Notre Dame Integrated Imaging Facility (NDIIF). "Actually, we are a CTSI [Clini- cal and Translational Science Institute]- approved facility, so researchers at Indiana University, Purdue, and Notre Dame can use this facility at the internal rate." The facil- ity contains instrumentation for magnetic resonance (MR), SPECT, PET, and biolumi- nescence imaging, as well as electron micros- copy and traditional optical microscopy. At Notre Dame, the instruments being used are all built by Bruker. Todd Sasser, Ph.D., feld applications scientist for Bruker's preclinical imaging division, works closely with the NDIIF to support its Bruker prod- ucts, which include an Albira PET/SPECT/ CT imager. "It's an interesting time," notes Dr. Sasser. "The optical market has become more and more sensitive. We are almost at the theoretical limit of resolution for PET imagers, based on the physics of the posi- tron." The Albira II, which came out in 2010, has already been supplanted by a newer model called the Albira Si, which has a few unique differences from its predecessor, but is named for its use of silicon (Si) PMTs, which, as Dr. Sasser explains, pave the way for MR integration. "Standard PMTs," notes Dr. Sasser, "are not compatible with MR felds without shielding." Currently, animals must be manually transferred from one instrument to another for multimodal imaging. In the NDIIF TRANSLATIONAL MEDICINE See Imaging on page 32 > bioMérieux Acquires Hyglos Expanding into the detection of endotoxins, bioMérieux announced that it acquired Hyglos in a deal that will amount to €24 million ($27 mil- lion), phased over the next three years. "Hyglos' expertise in the feld of recombinant proteins opens new horizons for the detection of endo- toxins," said Nicolas Cartier, head of bioMérieux's industry unit. "We are convinced of the relevance of its in- novative method. Its existing product portfolio has enriched our ofering of microbiological control solutions for the pharmaceutical industry and medical devices." > Clinical Genomics Implements Laboratory Information Management System Clinical Genomics plans to in- tegrate UNIConnect LC's Precision Molecular Diagnostics (pMDx™) LIMS in its two laboratories. The pMDx soft- ware system is designed to facilitate automation of all laboratory pro- cesses from sample accessioning to fnancial clinical result reporting. Clinical Genomics aims to expand this technology to its MDx laborato- ries in Bridgewater, NJ, and Sydney, Australia. The company selected pMDx because of the system's fun- damental focus on the needs and processes of the molecular diagnos- tics laboratory and the key quality and operational checks integrated in the LIMS software. Clinical Genom- ics intends to use pMDx to advance its development of colorectal cancer diagnostics . > Strata Oncology, Thermo Fisher Scientifc Partner Strata Oncology has joined Ther- mo Fisher Scientifc in a partnership that allows Thermo to serve as the technology provider for Strata. Ther- mo will contribute Ion S5™ XL next- generation sequencing systems, Am- pliSeq™ technology, and Oncomine™ assays. "Thermo Fisher is committed to enabling its growing list of strate- gic partners to drive the era of preci- sion medicine through its targeted, next-generation sequencing technol- ogy, which will help laboratories and clinicians provide the best oncology treatment possible in the future," said Joe Bernardo, president of clinical se- quencing at Thermo Fisher . n News Molecular Diagnostics The Bruker Albira, a PET/SPECT/CT imaging s ys te m , i n o p e rat i o n at t h e U n i ve r s i t y o f Notre Dame. The trimodal system has allowed Notre Dame researchers to conduct preclinical s t u d i e s i n o n c o l o g y t h a t h a ve a d v a n c e d the development of novel radiotracers and therapeutics. Each imaging modality—MRI, PET, and SPECT—has its strengths and weaknesses.