Damage signature of fatigued fabric reinforced plastics in the pulsed ultrasonic polar scan

This study investigates the use of both the amplitude and time-of-flight based pulsed ultrasonic polar scan (P-UPS) for the nondestructive detection and evaluation of fatigue damage in fiber reinforced composites. Several thermoplastic carbon fabric reinforced PPS specimens (CETEX), loaded under various fatigue conditions, have been scanned at multiple material spots according to the P-UPS technique in order to extract material degradation in a quantitative way. The P-UPS results indicate that shear dominated fatigued carbon/PPS goes with a reduction of shear properties combined with large fiber distortions. The P-UPS results of the tension-tension fatigued carbon/PPS samples on the other hand reveal a directional degradation of the stiffness properties, reaching a maximum reduction of -12.8% along the loading direction. The P-UPS extracted damage characteristics are fully supported by simulations, conventional destructive tests as well as visual inspection. The results demonstrate the excellent capability of the P-UPS method for nondestructively assessing and quantifying both shear-dominated and tension-tension fatigue damage in fabric reinforced plastics

The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

YesNon-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.University of Bradfor

Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy

Molecular radiotherapy using 177Lu-DOTATATE is a most effective treatment for somatostatin receptor-expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor. Here, we visualized and quantified the extent of DNA damage response after 177Lu-DOTATATE therapy using SPECT imaging with 111In-anti-γH2AX-TAT. This work was a proof-of-principle study of this in vivo noninvasive biodosimeter with β-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external-beam radiotherapy (EBRT) or 177Lu-DOTATATE, after which the number of γH2AX foci and the clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor-positive tumor xenografts were treated with 17

In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT.

UNLABELLED: The application of 123I-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125I-2-iodo-L-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates 123I-2-iodo-L-phenylalanine as a new specific tumor tracer for SPECT. METHODS: 123/125I-2-Iodo-L-phenylalanine is prepared as a one-pot kit using the Cu1+-assisted isotopic exchange method. The characteristics of 125I-2-iodo-L-phenylalanine were examined in vivo in R1M tumor-bearing athymic mice and in acute inflammation-bearing NMRI mice. The uptake of 123/125I-2-iodo-L-phenylalanine in tumor and other organs of interest was measured by dynamic planar imaging (DPI) and gamma-counting after dissection. Displacement of 123I-2-iodo-L-phenylalanine radioactivity by L-phenylalanine, L-methionine, and L-cysteine was measured. 123I-Iodo-human serum albumin planar imaging was performed to correct for blood-pool activity and MRI was performed to delineate the tumor in DPI. 18F-FDG uptake was measured with an animal PET scanner. 125I-2-Iodo-L-phenylalanine and 18F-FDG uptake in inflamed muscle were compared. RESULTS: 123/125I-2-Iodo-L-phenylalanine showed a high and fast tumor uptake and followed a reversible first-order pattern allowing calculation of the half-life and the time to reach equilibrium (t(R)). Net tumor-to-background ratios up to 6.7 at 60 min were obtained. This radioactivity was significantly displaced by L-phenylalanine, L-methionine, and L-cysteine, pointing to reversible LAT transport. When plotting t(R) of the tumor uptake as a function of tumor volume, a rectangular hyperbolic curve was obtained. The almost constant t(R) values at higher tumor volumes (>4 mL) could be linked to increased necrotic tissue. Fast blood clearance of the tracer through the kidneys to the bladder and low tracer activity in the abdomen and brain were observed. The inflamed muscle showed only a slight increase of 125I-2-iodo-L-phenylalanine uptake (inflammation-to-background ratio, RIB = 1.30 +/- 0.02), in contrast to the high 18F-FDG uptake (RIB = 11.1 +/- 1.7). The in vivo stability of 123/125I-2-iodo-L-phenylalanine was good: Only 7% of free radioiodide and no other labeled metabolites were observed after 90 min. CONCLUSION: 123/125I-2-Iodo-L-phenylalanine is quickly taken up by the overexpressed LAT1 system in R1M tumors with high tumor specificity. The availability of a kit and the specificity of the tracer make 123I-2-iodo-L-phenylalanine a promising tool for oncologic SPECT