Radiation Medicine Commons^™

Radiation-Induced Gastrointestinal (Gi) Syndrome As A Function Of Age, Hongyan Li, Herman C. Kucharavy, Carla Hajj, Liyang Zhao, Guoqiang Hua, Ryan Glass, Phillip B. Paty, Zvi Fuks, Richard Kolesnick, Karen Hubbard, Adriana Haimovitz-Friedman

Publications and Research

Previous studies show increased sensitivity of older mice (28–29 months) compared with young adult mice (3 months, possessing a mature immune system) to radiation-induced GI lethality. Age-dependent lethality was associated with higher levels of apoptotic stem cells in small intestinal crypts that correlated with sphingomyelinase activity, a source of pro-apoptotic ceramide. The objective of this study is to determine whether the cycling crypt base columnar cells (CBCs) in aging animals are specifically more sensitive to radiation effects than the CBCs in young adult mice, and to identify factors that contribute to increased radiosensitivity. Mortality induced by subtotal body radiation was …

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

Discriminating Radiation Injury From Recurrent Tumor With [18f]Parpi And Amino Acid Pet In Mouse Models, Patrick L. Donabedian, Susanne Kossatz, John A. Engelbach, Stephen A. Jannetti, Brandon Carney, Robert J. Young, Wolfgang A. Weber, Joel R. Garbow, Thomas Reiner

Publications and Research

Background

Radiation injury can be indistinguishable from recurrent tumor on standard imaging. Current protocols for this differential diagnosis require one or more follow-up imaging studies, long dynamic acquisitions, or complex image post-processing; despite much research, the inability to confidently distinguish between these two entities continues to pose a significant dilemma for the treating clinician. Using mouse models of both glioblastoma and radiation necrosis, we tested the potential of poly(ADP-ribose) polymerase (PARP)-targeted PET imaging with [¹⁸F]PARPi to better discriminate radiation injury from tumor.

Results

In mice with experimental radiation necrosis, lesion uptake on [¹⁸F]PARPi-PET was similar to …

Tmsotf Assisted Synthesis Of 2’-Deoxy-2’-[18f] Fluoro-Β-D-Arabinofuranosylcytosine ([18f] Fac), Kishore K. Gangangari, John L. Humm, Steven M. Larson, Naga Vara Kishore Pillarsetty

Publications and Research

[¹⁸F]FAC (2’-deoxy-2’-[¹⁸F]fluoro-β-D-arabinofuranosylcytosine, 1) is a versatile probe for imaging deoxycytidine kinase (dCK) expression levels in vivo. dCK is responsible for phosphorylation of deoxycytidine (dC, 2) and other nucleoside analogs, plays a key role in immune activation and has demonstrated to be one of the key enzymes in activating nucleoside based drugs including gemcitabine. Reported synthesis of [¹⁸F]FAC is high yielding but is quite challenging requiring bromination using HBr and careful drying of excess HBr which is critical for successful synthesis. Here in we report a simplified trimethylsilyl trifluoromethanesulfonate (TMSOTf) assisted synthesis …