10 research outputs found
Renormalization of radiobiological response functions by energy loss fluctuations and complexities in chromosome aberration induction: deactivation theory for proton therapy from cells to tumor control
We employ a multi-scale mechanistic approach to investigate radiation induced
cell toxicities and deactivation mechanisms as a function of linear energy
transfer in hadron therapy. Our theoretical model consists of a system of
Markov chains in microscopic and macroscopic spatio-temporal landscapes, i.e.,
stochastic birth-death processes of cells in millimeter-scale colonies that
incorporates a coarse-grained driving force to account for microscopic
radiation induced damage. The coupling, hence the driving force in this
process, stems from a nano-meter scale radiation induced DNA damage that
incorporates the enzymatic end-joining repair and mis-repair mechanisms. We use
this model for global fitting of the high-throughput and high accuracy
clonogenic cell-survival data acquired under exposure of the therapeutic
scanned proton beams, the experimental design that considers -H2AX as
the biological endpoint and exhibits maximum observed achievable dose and LET,
beyond which the majority of the cells undergo collective biological
deactivation processes. An estimate to optimal dose and LET calculated from
tumor control probability by extension to cells per -size voxels
is presented. We attribute the increase in degree of complexity in chromosome
aberration to variabilities in the observed biological responses as the beam
linear energy transfer (LET) increases, and verify consistency of the predicted
cell death probability with the in-vitro cell survival assay of approximately
100 non-small cell lung cancer (NSCLC) cells
Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease
© 2020, The Author(s). Objective: Expression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study. Methods: Three IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50–70 bone, SUVr50–70 blood, respectively) and PET volume of distribution (VT) of the radioligand were calculated. Results: A mean [11C]PBR28 radioactivity of 378 (range 362–389) MBq was administered. A significant decrease (p < 0.05) in VT, SUVr50–70 bone and SUVr50–70 blood observed after oral emapunil confirmed the TSPO specificity of [11C]PBR28. A decrease in SUV was not observed in the post-block scan. Conclusion: [11C]PBR28 is TSPO-specific radioligand in IJD patients. Simplified PET protocols with static PET acquisition can be used in the management and evaluation of novel therapeutics that target TSPO overexpressing cells
Integrin αvβ6 Positron Emission Tomography Imaging in Lung Cancer Patients Treated With Pulmonary Radiation Therapy
© 2020 Elsevier Inc. Purpose: Post radiation therapy (RT) lung fibrosis is a major barrier to improved cure rate in lung cancer. Integrin αvβ6 plays a key role in fibrogenesis by activating transforming growth factor-β. Positron emission tomography (PET) studies with a fluorine-18 radiolabelled αvβ6 radioligand, [18F]-FBA-A20FMDV2, were performed to assess uptake, and the relationship to RT dose parameters was explored. Methods and Materials: Recently treated non-small cell lung cancer patients (40 Gy (excluding tumor), 25 to 40 Gy, 15 to 25 Gy, 8 to 15 Gy, and < 8 Gy. PET uptake (standardized uptake value; SUV) corrected for tissue density between 10 and 60 minutes (SUV10-60) was calculated and compared with RT dose, dose per fraction, and biological effective dose (BED). PET uptake was also evaluated in healthy volunteers.ResultsSix non-small cell lung cancer (3 male; 3 female) subjects scanned between 6 and 22 weeks after RT and 6 healthy volunteers (3 males; 3 females) were evaluated. Higher mean PET uptake (SUV10-60) was observed in the irradiated lung compared with the healthy lung (2.97 vs 1.99; P < .05). A significant and positive pharmacodynamic relationship was observed between radioligand uptake (SUV10-60) and dose per RT fraction (r2 = 0.63; P < .001) and with BED for fibrosis (r2 = 0.38; P < .001 for α/β 3 Gy and r2 = 0.33; P < 0.001 for α/β 5 Gy).ConclusionsHigher uptake in the irradiated lung and a pharmacodynamic relationship between αvβ6 radioligand uptake versus RT dose per fraction and BED for lung fibrosis is consistent with RT induced activation of αvβ6 integrin and supports a role for αvβ6 in the induction of lung fibrosis after pulmonary RT. αvβ6-PET imaging may potentially aid in the assessment and management of radiation-induced pulmonary fibrosis