Metabolic Imaging of Early Radiation-Induced Lung Injury Using Hyperpolarized 13C-Pyruvate in Rodent Lungs

Lung cancer is the leading cause of cancer related death. Radiation therapy is a prominent treatment method but leads to adverse consequences. Radiation-Induced Lung Injury (RILI) is the primary adverse consequence that limits further radiation therapy and develops in 5-37% of the treated patients. RILI proceeds in two distinct phases: a) early and reversible Radiation Pneumonitis (RP), and b) late and irreversible radiation fibrosis. Clinically, Dose Volume Histogram (DVH) parameters derived from radiation therapy planning stage are used to determine outcome and severity of RP but have been demonstrated to possess a very low predictive power. Computed Tomography (CT) is the most commonly used modality for the imaging of RP, but often only detects very late RP that leaves little room for intervention to abort the progress to irreversible radiation fibrosis. Early detection of RP using imaging may allow for interventional treatment and management of the disease and the associated symptoms in a better manner. Improvement in Dynamic Nuclear Polarization (DNP) technology has led to advancement of hyperpolarized 13-Carbon-Magnetic Resonance Imaging (13C-MRI). In this thesis, we present the investigation of early detection of RP with 13C-MRI in an animal model with the use of hyperpolarized 13C-pyruvate. A pilot study demonstrated the proof of concept along with a qualitative histological confirmation. 13C-MRI data and histology data were collected 2 weeks post irradiation of whole thorax in rodents. In the subsequent study, regional and longitudinal 13C-MRI and quantitative histology data were analyzed to demonstrate the early organ-wide response of RP. These data were collected at day 5, 10, 15 and 25 post conformal irradiation of the right rodent lung. Finally, we demonstrate a novel approach to map pH using hyperpolarized 13C-bicarbonate with the use of spiral-Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) pulse sequence. Validation of this approach by comparison to Chemical Shift Imaging (CSI) pH measurement and standard pH measurement with the aid of phantoms along with hyperpolarized 13C-bicarbonate is presented. pH mapping may play a role in the staging and therapeutic intervention of cancer

How and Why Are Cancers Acidic? Carbonic Anhydrase IX and the Homeostatic Control of Tumour Extracellular pH.

The acidic tumour microenvironment is now recognized as a tumour phenotype that drives cancer somatic evolution and disease progression, causing cancer cells to become more invasive and to metastasise. This property of solid tumours reflects a complex interplay between cellular carbon metabolism and acid removal that is mediated by cell membrane carbonic anhydrases and various transport proteins, interstitial fluid buffering, and abnormal tumour-associated vessels. In the past two decades, a convergence of advances in the experimental and mathematical modelling of human cancers, as well as non-invasive pH-imaging techniques, has yielded new insights into the physiological mechanisms that govern tumour extracellular pH (pHe). In this review, we examine the mechanisms by which solid tumours maintain a low pHe, with a focus on carbonic anhydrase IX (CAIX), a cancer-associated cell surface enzyme. We also review the accumulating evidence that suggest a role for CAIX as a biological pH-stat by which solid tumours stabilize their pHe. Finally, we highlight the prospects for the clinical translation of CAIX-targeted therapies in oncology

EPR Effect-Based Tumor Targeted Nanomedicine

I am honored to undertake the work for Guest Editor for this Special Issue of EPR Effect-Based Tumor Targeted Nanomedicine for the Journal of Personalized Medicine. It has already been 35 years since we published the concept of the EPR effect for the first time. The discovery of the new concept of EPR effect gave an impetus effect of growth momentum in nanomedicine, and numerous works are focused on tumor delivery, although the initial idea was based on vascular permeability in infection-induced inflamed tissue, where we discovered bradykinin in the key mediator of vascular permeability.I know, however, there are pros and cons to EPR effect. Cons stem either from a poor understanding of EPR effect, or somehow a biased view of the EPR effect, or from the tumor models being used, particularly in the clinical settings where vascular blood flow is so frequently obstructed. I hope scientists in the clinic, or basic researchers working on the tumor drug delivery, will join the forum of this Special Issue and express their data and opinions.The scope of this issue includes an in-depth understanding of the EPR effect, and issues associated with tumor microenvironment and also further exploitation of EPR effect in human cancer. In addition, new strategies for enhancement of the EPR effect using nanomedicine will be welcome, which is as important as the EPR effect itself. These papers cover not only cancer therapy, but also imaging techniques using nanofluorescent agents, including photodynamic therapy for inflammation, and boron neutron capture therapy

Glioma

The tittle 'Glioma - Exploring Its Biology and Practical Relevance' is indicative of its content. This volume contains 21 chapters basically intended to explore glioma biology and discussing the experimental model systems for the purpose. It is hoped that the present volume will provide supportive and relevant awareness and understanding on the fundamental advances of the subject to the professionals from any sphere interested about glioma

Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis

This book focuses on how nanoscale systems can be used to deliver molecules to help with cancer management. It provides a broad overview of some of the key strategies for nanocarrier design. These strategies are brought together by the wide compositional variety of these systems and the diversity of molecules that may be carried. Additionally, functionalization strategies, codelivery, and combination with other treatment modalities highlight a very active research field

Brain tumors: preclinical imaging and novel therapies

Vandertop, W.P. [Promotor]Würdinger, T. [Promotor]Noske, D.P. [Copromotor]Hulleman, E. [Copromotor

Cancer Nanomedicine

This special issue brings together cutting edge research and insightful commentary on the currentl state of the Cancer Nanomedicine field

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog