NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Purpose: The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [18F]fluoromisonidazole ([18F]FMISO). Methods: [18F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [18F]fluorodeoxyglucose ([18F]FDG) PET scans were also performed in the mice bearing human tumour xenografts. Results: In 10 out of 11 experimental tumour models, [18F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR75% and TMRR5 (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [18F]FMISO uptake in the tumours. The variability observed in [18F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [18F]FDG and [18F]FMISO images. Conclusion: This study demonstrates the feasibility and utility of [18F]FMISO for imaging murine tumour models using NanoPE

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Purpose: The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [18F]fluoromisonidazole ([18F]FMISO). Methods: [18F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [18F]fluorodeoxyglucose ([18F]FDG) PET scans were also performed in the mice bearing human tumour xenografts. Results: In 10 out of 11 experimental tumour models, [18F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR75% and TMRR5 (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [18F]FMISO uptake in the tumours. The variability observed in [18F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [18F]FDG and [18F]FMISO images. Conclusion: This study demonstrates the feasibility and utility of [18F]FMISO for imaging murine tumour models using NanoPE

Quality of Animal Experiments in Anti-Angiogenic Cancer Drug Development – A Systematic Review

<div><p>Translation from preclinical animal research to clinical bedside has proven to be difficult to impossible in many fields of research (e.g. acute stroke, ALS and HIV vaccination development) with oncology showing particularly low translation rates (5% vs. 20% for cardiovascular diseases). Several investigations on published preclinical animal research have revealed that apart from plain species differences, translational problems can arise from low study quality (e.g. study design) or non-representative experimental conditions (e.g. treatment schedule).</p><p>This review assessed the published experimental circumstances and quality of anti-angiogenic cancer drug development in 232 in vivo studies. The quality of study design was often insufficient; at least the information published about the experiments was not satisfactory in most cases. There was no quality improvement over time, with the exception of conflict of interest statements. This increase presumably arose mainly because journal guidelines request such statements more often recently.</p><p>Visual inspection of data and a cluster analysis confirmed a trend described in literature that low study quality tends to overestimate study outcome. It was also found that experimental outcome was more favorable when a potential drug was investigated as the main focus of a study, compared to drugs that were used as comparison interventions. We assume that this effect arises from the frequent neglect of blinding investigators towards treatment arms and refer to it as hypothesis bias.</p><p>In conclusion, the reporting and presumably also the experimental performance of animal studies in drug development for oncology suffer from similar shortcomings as other fields of research (such as stroke or ALS). We consider it necessary to enforce experimental quality and reporting that corresponds to the level of clinical studies. It seems that only clear journal guidelines or guidelines from licensing authorities, where failure to fulfill prevents publication or experimental license, can help to improve this situation.</p></div

Cognitive neuroscience and brain imaging

Imaging technologies have experienced rapid progress and are currently used widely both in medical diagnostics and in research. Imaging beyond X-ray and standard MRI became established in recent years. The extended set of imaging methodologies available allows methods to be selected according to the actual needs or even the combination of different imaging principles to obtain further improved read-outs. The symposium consisted of four overview lectures. Three speakers from academia and one speaker from industry described different techniques, recent developments and future needs from various perspectives in the lectures entitled: Non-Invasive Imaging in Biomedical Research: Annotating Structure with Molecular Information; Molecular Imaging with PET Tracers and Animal PET Scanners; Nuclear (PET- and SPECT-) Imaging Agents from Research to Approval (Perspectives from a Pharma Company Working on in vivo Diagnostics); Cognitive Neuroscience and Brain Imaging

Contingency table of relative outcome distribution within interventions in main focus of a study or comparison interventions.

<p>Relative distribution of positive (1–3), rather neutral (4a) and negative (4b) outcome within the study parameter “function of intervention”.</p><p>Contingency table of relative outcome distribution within interventions in main focus of a study or comparison interventions.</p

Frequency of experimental outcome 4 (progression) for studies with the same quality score.

<p>n = 891.</p

Variable distribution within the four identified clusters.

<p>SEM = standard error of the mean; SD = standard deviation; NA = not available. Uniform Outcome: 1 = Cure, 2 = Regression, 3 = Stable Disease, 4a = Moderate Progression, 4b = Progression, 5 = NA.</p><p>Variable distribution within the four identified clusters.</p

Parameters referring to each study as a whole.

<p>Parameters referring to each study as a whole.</p