2023 MIPS Molecular Imaging Seminar Series

Prof. Xiaoyuan (Shawn) Chen received his PhD in Chemistry from the University of Idaho (1999). After being a faculty at the University of Southern California, Stanford University and then Senior Investigator/Lab Chief at the National Institutes of Health, he is now Nasrat Muzayyin Professor in Medicine and Technology, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore. His current research interests are mainly theranostics (radiotheranostics, nanotheranostics, immunotheranostics, magnetotheranostics, phototheranostics, etc.) that can be clinically translatable. He has published over 900 papers and numerous books (Total citations > 110,000, H index 176 based on Google scholar). He was elected as AIMBE Fellow (2017) and SNMMI Fellow (2020), received SNMMI Michael J. Welch Award (2019), ACS Bioconjugate Chemistry Lecturer Award (2016), NIH Director’s Award (2014), NIBIB Mentor Award (2012). He is also the Past President of Chinese-American Society of Nuclear Medicine and Molecular Imaging (CASNMMI), Past President of the Radiopharmaceutical Science Council (RPSC), Society of Nuclear Medicine and Molecular Imaging (SNMMI), and Past President of the Chinese American Society of Nanomedicine and Nanobiotechnology (CASNN).

Tumor acidosis, hypoxia and vascular perfusion are well-known characteristics of the tumor microenvironment.  We have developed MRI, PET/MRI, multispectral optoacoustic tomography (MSOT) and electron paramagnetic resonance imaging (EPRI) to measure extracellular pH, oxygenation and pharmacokinetics transport rates in solid tumors.  We apply these molecular imaging methods to preclinical tumor models, and we have translated some of our methods to evaluate patients who have cancer.  We are especially focused on employing molecular imaging to predict treatment effect before starting therapy, and to evaluate the early response to treatment, during evaluations of chemotherapy, radiotherapy and immunotherapy.

Dr. Marty Pagel is a Professor in the Departments of Cancer Systems Imaging and Imaging Physics at the University of Texas MD Anderson Cancer Center. His research in academia and industry has evolved from chemistry to biomedical engineering to molecular imaging.  His current research  employs a variety of imaging modalities to interrogate biomarkers of the tumor microenvironment. He has developed these methods for pre-clinical and clinical imaging, especially to evaluate cancer therapies. In addition, Dr. Pagel has taught many courses in chemistry, biomedical engineering and cancer biology, and many workshops about scientific writing. Dr. Pagel has held many leadership positions in the molecular imaging research community, including roles in scientific societies, many grant review panels, and journals focused on molecular imaging. 

Advances in radionuclide therapy research and recent approvals are poised to change the management landscape for many cancer patients. Here, the potent emissions of systemically administered radionuclides are designed to specifically target lesions throughout the body. The goal is to achieve cytotoxic absorbed doses at sites of disease while sparing normal organs. Currently, administered activities are based on mass rather than disease features, genomic characteristics or patient histories. Information about the multi-scale pharmacokinetics of these agents can be accessed by noninvasive imaging methods. This talk will detail our efforts to quantitatively determine parameters that inform treatment optimization at the tissue scale through to the patient scale, using conventional and novel imaging methods in molecular imaging. 

Dr. Thorek has a background in engineering and biomedical imaging. His laboratory of biologists, chemists, engineers and physicists is concerned with multidisciplinary technology development and translational radiopharmaceutical drug design. Dr. Thorek completed hisdoctorate at the University of Pennsylvania in 2010, focused on the use of novel contrast agents in imaging of immunotherapy responses, cellular inflammatory processes, and in cancer diagnosis. This work primarily used magnetic resonance, optical and molecular biology techniques. He followed with a postdoctoral fellowship at Memorial Sloan Kettering Cancer Center in nuclear medicine as an R25T Molecular Imaging Fellow. The concentration of this work was on methods for targeted and functional imaging of metastases, in the lymphatics and the osseous microenvironment. Dr. Thorek was initially appointed as an Assistant Professor of Radiology at Johns Hopkins University in 2014, before moving his laboratory to Washington University in 2018. His team's research pursuits are directed at improved characterization of disease by noninvasive imaging; quantitative imaging to guide personalized therapy; and nuclear oncology drug development. Broadly, his lab use pre- and clinical imaging information to both select and refine theranostics, and to augment precision prescription of particle emitting radiotherapies. Current work involves radioisotope production, overcoming challenges in radiopharmaceutical quality control, pre- and clinical imaging of targeted therapies, and patient-based microdosimetric alpha particle computation.

The metabolism of T cells and other immune cells is dynamically regulated and influences biosynthesis, signaling, and cell fate. We have shown that CD4 T cell subsets are metabolically distinct and that each requires a specific metabolic program for their function. Effector T cell fates (such as Th1, Th2, Th17) activate a highly glycolytic program while regulatory T cells (Treg) utilize a more oxidative metabolism and oxidize lipids and pyruvate as major fuels. We are now engaged in efforts to identify new immunometabolic mechanisms that influence T cell fate and offer approaches to manipulate immunity. It is clear, however, that tissue microenvironments also influence these processes. To address these cell-extrinsic factors we have studied obesity and fever temperatures as regulators of immune cell metabolism and fate. Obesity is associated with increased risk of cancer while paradoxically enhancing the efficacy of immune therapy in some cases. We found that tumors in obese individuals and animals have increased frequencies of PD-1+ macrophages and that PD-1 is a direct regulator of macrophage metabolism and ability to present antigen and stimulate T cells. Macrophages induced PD-1 in response to multiple inflammatory cytokines as well as leptin and insulin and PD-1-deficient macrophages had increased glycolysis and anti-tumor activity. These data show that obesity restrains anti-tumor immunity in part through PD-1-mediated inhibition of macrophage function. Local and systemic fevers are also closely associated with inflammation. We tested how elevated temperature affected T cell metabolism and fate and found that fever temperatures could alter metabolism and promote apoptosis of Th0 and Th1 cells. Interestingly, this did not occur for Treg or Th17 cells and appeared due to mitochondrial dysfunction and ROS that lead to DNA damage. A CRISPR screen of cell death mechanisms showed Th1 cell apoptosis was largely due to the tumor suppressor p53, and Tp53 /- T cells better survived and were enriched in a model of inflammatory bowel disease (IBD). Consistent with animal models, human IBD and rheumatoid arthritis showed IFNγ-producing T cells to be both highly glycolytic and with evidence of DNA damage. These data suggest that fever temperatures both enhance inflammation and lead to DNA damage that requires p53-dependent apoptosis to maintain genomic integrity. Together, our studies show that understanding both cellular and microenvironmental mechanisms that regulate T cell metabolism may provide new tools to understand and modulate immunity the balance of T cell effector and regulatory populations.

Dr. Jeffrey Rathmell studies how T cells influence inflammatory diseases and cancer with a focus on metabolic mechanisms that regulate lymphocyte fate and differentiation.  He has an interdisciplinary research program using genetic and biochemical approaches to discover mechanisms of immunometabolism that drive or influence immune-related diseases.  Following a PhD in Immunology at Stanford University and postdoctoral studies at the University of Pennsylvania, his work as faculty at Duke University and Vanderbilt University showed that the metabolism of lymphocytes was dynamically regulated, and was the first to show that each T cell subset adopts a specific metabolic program that can be targeted to modulate cell function and fate. He has shown that the tumor microenvironment influences T cell metabolism and that immune cells contribute significantly to overall tumor glucose uptake. He joined Vanderbilt in 2015 to found and direct the Vanderbilt Center for Immunobiology and is Leader for the Vanderbilt Ingram Cancer Center Program in Host-Tumor Interactions.  His awards include Scholar of the Leukemia & Lymphoma Society, Bernard Osher Fellow of the American Asthma Foundation, and William Paul Distinguished Innovator of the Lupus Research Alliance.

Dr. Lundberg is Associate Professor of Bioengineering and Pathology at Stanford University, and Director of the Cell Atlas, of the Human Protein Atlas program. In the interface between bioimaging, proteomics and artificial intelligence her research aims to define the spatiotemporal subcellular architecture of the human proteome, to understand how variations in protein expression patterns contribute to cellular function and disease. Dr. Lundberg has a keen interest in citizen science using computer games, and has engaged over 300,000 gamers to help her classify images in the first ever MMO citizen science computer game.

The dynamic cellular ecosystem of a growing tumour mass requires a vascular network to obtain oxygen and nutrients, as well as to remove metabolic waste products. Early in their development, tumours stimulate new blood vessel growth through a range of mechanisms to meet this need, leading to marked differences between normal and tumour tissue that could be exploited for early cancer detection.

The structure and function of the tumour vasculature can be revealed using optics, thanks to the strong absorption of light by oxy- and deoxy-haemoglobin. Hyperspectral imaging is a new frontier in medical physics that enhances colour vision and enables measurement of the local concentration and oxygenation of haemoglobin. To extract quantitative biomarkers from hyperspectral images, we combine novel optical sampling methods with advanced computational analysis and biophysical modelling, applied in both preclinical cancer models and early phase clinical trials in patients. In this talk, I will give an overview of our recent clinical findings and current research based on hyperspectral imaging.

Sarah Bohndiek completed her PhD in Radiation Physics at University College London in 2008 and then worked in both the UK (at Cambridge) and the USA (at Stanford) as a postdoctoral fellow in molecular imaging. Sarah joined the University of Cambridge in 2013, where she is jointly appointed as a Professor of Biomedical Physics in the Department of Physics and at the Cancer Research UK Cambridge Institute. Sarah was elected Fellow of the international optics and photonics society SPIE in 2020.

Sarah’s interdisciplinary team, the VISIONLab, are pushing the boundaries of optical imaging technology to address the major unmet clinical need for earlier cancer detection. The VISIONLab create innovative methods to visualize complex biological processes in situ using light and enable translation of their measurements into meaningful insights through early stage testing in model systems and human trials.

In addition to her research programme, Sarah also takes a pro-active role in teaching and mentoring the next generation of scientists. She has acted as an ambassador for public and media engagement as well as interdisciplinary research training throughout her career.

The Manning Laboratory at MD Anderson develops and evaluates radiopharmaceuticals for diagnosis and therapy. Many diagnostic- and therapeutics discovery-based projects in our lab focus on molecular targets related to cancer cell metabolism, with recent emphases on solute carrier-based amino acid transport. In my lecture, I will describe a number of biologically and clinically-driven programs we are pursuing in multi-disciplinary and collaborative fashion, ranging from discovery to clinical trials. I will all also touch on new radiochemistry technologies that enable dose-scale radiopharmaceutical production using inexpensive and disposable microfluidic devices.

H. Charles Manning is a chemist with a background in radiochemistry, medicinal chemistry and imaging science. Continuously supported by the National Cancer Institute (NCI) throughout his career, as well as the DOD, industry and philanthropy partners, Dr. Manning’s lab discovers and translates novel radiopharmaceuticals for imaging and therapy. After beginning his independent research career at Vanderbilt in 2006, the Manning Laboratory was recruited to MD Anderson Cancer Center in Houston, Texas in September, 2020. At MD Anderson, Dr. Manning is a Professor in the Department of Cancer Systems Imaging and serves as the Scientific Director of the Center for Advanced Biomedical Imaging (CABI) and Director of the Cyclotron Radiochemistry Facility. He co-leads the Institutional Theranostics Program and is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar. Many radiopharmaceutical- and drug development-based projects in the Manning laboratory focus on molecular targets related to cancer cell metabolism, with current emphases on solute carrier-based amino acid transport. In addition to these biologically- and clinically-driven programs, the Manning laboratory is developing new radiochemistry technologies that enable dose-scale radiopharmaceutical production using inexpensive and disposable microfluidic devices.

In the realm of life sciences, the long-held aspiration for a three-dimensional magnifying glass capable of unveiling a spectrum of tissue functions and structures in a single comprehensive scan has driven innovation in imaging technology. This pursuit has culminated in the creation of a groundbreaking preclinical imaging platform with the capacity to map intricate dynamics of contrast agents, tracers, radiopharmaceuticals, receptors, and therapy response indicators within organs and tumors. Our endeavor has resulted in the development of an intuitively navigable, fully integrated modular PET-SPECT-Optical-CT imaging platform, honored with e.g. the prestigious WMIC Innovation of the Year award.

The platform's pivotal features encompass:

1. Ultra-high Precision: Achieving an astounding 0.12 mm SPECT and 0.6 mm PET resolution, the PET component boasts the unique ability to mitigate positron-range effects. Furthermore, it enables concurrent sub-millimeter multi-tracer PET-PET and PET-SPECT imaging. This innovation extends to encompass sub-second dynamic nuclear imaging, with proprietary high-energy SPECT technology empowering sub-mm resolution imaging of alpha (α) and beta (β) emitters such as 223Ra, 213Bi, 131I, 209At, and 225Ac.
2. High Structural Clarity: The platform integrates an ultra-high-resolution X-ray CT component that not only excels in capturing minute details but also operates at remarkably low radiation doses, underscoring its commitment to safety.
3. Fluorescence/Bioluminescence Mastery: Delivering on the demand for high-throughput imaging, the platform also encompasses comprehensive fluorescence and bioluminescence imaging capabilities, further enriched by quantitative optical tomography.

Our visionary platform is ingeniously designed to facilitate the seamless fusion of various modalities, allowing for an array of customized imaging combinations. During this presentation, we will unravel the adaptive nature and versatility of this molecular and structural imaging marvel. Alongside this exploration, we will delve into the manifold scientific and industrial applications that stand to be revolutionized by this pioneering advancement.

Prof. Freek Beekman leads the Biomedical Imaging section at Delft University of Technology. He has (co-)authored numerous scientific papers and is inventor of > 20 life patent families. He has received multiple awards in acknowledgment of his innovations.

His research spans diverse interests, including detector advancement, PET/SPECT/X-ray CT image reconstruction, hybrid imaging, and AI. He's an associate editor for esteemed journals Biomedical Engineering and IEEE TMI.

In 2006, he founded MILabs, a pioneering company developing high-performance imaging systems. As MILabs' CEO from 2006 to 2021, he orchestrated its successful acquisition by Rigaku in Japan.

Today, systems developed by Prof. Beekman and his collaborative teams at TU Delft and MILabs are vital in global biomedical research institutions, propelling discoveries, tracer development, and pharmaceutical progress.

Prof. Dr. Bernd Pichler is director of the Werner Siemens Imaging Center and chair of the Department of Preclinical Imaging and Radiopharmacy, Clinic of Radiology, University of Tübingen, Germany, as well as the Dean of the Faculty of Medicine at the Eberhard Karls University of Tübingen, Germany. He earned his PhD in physics at the Department of Nuclear Medicine (Prof. Markus Schwaiger), Technical University of Munich, and the Max-Planck Institute for Physics (Prof. Norbert Schmitz), Munich, in 2002 and subsequently worked at the Department of Biomedical Engineering (Prof. Simon Cherry), University of California, Davis, USA. In 2005 Bernd Pichler became head of the Laboratory for Preclinical Imaging and Imaging Technology at the University of Tübingen. In December 2007, Dr. Pichler accepted the call of the University of Tübingen for a full (W3) professorship in “Preclinical Imaging and Imaging Technology”. In 2008 he became head of the Radiopharmacy and in 2011 both, the Laboratory for Preclinical Imaging of the Swiss Werner Siemens-Foundation and the Radiopharmacy joined, to become the Department of Preclinical Imaging and Radiopharmacy, with Prof. Pichler as director and chair of the department. In May 2020 he was elected dean of the Medical Faculty of the University of Tübingen.