Radiation-induced lung injury is highly complex and characterized by multiple pathologies, which occur over time, and sporadically throughout the lung. This complexity makes biomarker investigations and medical countermeasure screenings challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has the ability to spatially resolve differences in molecular profiles within the lung following radiation exposure and can aid in biomarker identification and pharmaceutical efficacy investigations. MALDI-MSI was applied to the investigation of a whole-thorax lung irradiation model in non-human primates (NHP) for lipidomic analysis and medical countermeasure distribution.

Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well-established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of inter-dependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, we demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart, b) an extensive database in normal age-matched NHP for key primary and secondary endpoints, c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart.

promoted growth of prostate cancer (Pca) through increase of serum testosterone level and AR-dependent pathway. In this study, we further investigated the effect of CS on radio-sensitivity of androgen-responsive Pca. Materials/Methods: Androgen-responsive Pca cell line (VCaP) was incubated with 20 mg/ml CS extract for 96 h and then irradiated with a single dose of 0 Gy, 2 Gy, 4 Gy, and 6 Gy, respectively. Colonies were counted after 14 days incubation with the same culturing condition as pretreatment and dose-survival curves were plotted on a log-linear scale using the single-hit and multi-target model formula: SFZ 1e(1ee -kD ) N . Parameters such as mean lethal dose (D0), quasi-threshold dose (Dq) required to overcome the width of shoulder of the survival curve, which represents the ability of cells to repair the sublethal damage, and extrapolation number (N) that represents the theoretical target number, were estimated from the survival curves. Furthermore, apoptosis was examined in the Pca cells treated with or without the CS extract during and after exposure to 4 Gy irradiation using Annexin V-FITC/PI dual staining assays and flow cytometry analysis. Results: Significantly higher survival fractions (SF) were found in the Pca cells treated with CS extract after a single treatment of irradiation compared with control (2-Gy SF, 63.8AE13.7% for CS vs.46.5AE3.6% for control, pZ0.28; 4-Gy SF, 24.1 AE 0.6% for CS vs.13.6 AE 1.9% for control, pZ0.006; 6-Gy SF, 6.5 AE 0.2% for CS vs. 3.8 AE 0.8% for control, pZ0.03). The parameters D0, Dq, and N in the control group were 1.5, 1.07, and 2.05, respectively, while in the CS-treated group, the parameters were 1.65, 1.75, and 2.90, respectively. Furthermore, a much higher percentage of the CS-treated cells survived after the exposure to 4 Gy compared with control (92.1% for CS vs. 83.5% for control). Accordingly, rates of apoptosis in the CS-treated cells were significantly lower after 4 Gy irradiation (early apoptosis, 1.17% for CS vs.2.52% for control; late apoptosis and necrosis, 5.76% vs. 11.1%). Conclusion: Results of this study suggest that the CS significantly decreases radiosensitivity and enhances cell survival in Pca cells after radiation treatment. Additional studies are required to assess this negative impact on Pca growth by intake of CS during a clinical course of prostatic irradiation.