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Torigian D.A.,University of Pennsylvania | Lopez R.F.,HHUU Virgen del Rocvo | Alapati S.,University of Pennsylvania | Bodapati G.,University of Pennsylvania | And 4 more authors.
Hellenic Journal of Nuclear Medicine | Year: 2011

Our aim was to assess feasibility and performance of novel semi-automated image analysis software called ROVER to quantify metabolically active volume (MAV), maximum standardized uptake value-maximum (SUV max), 3D partial volume corrected mean SUV (cSUV mean), and 3D partial volume corrected mean MVP (cMVP mean) of spinal bone marrow metastases on fluorine-18 fluorodeoxyglucose-positron emission tomography/computerized tomography ( 18F-FDG-PET/CT). We retrospectively studied 16 subjects with 31 spinal metastases on FDG-PET/CT and MRI. Manual and ROVER determinations of lesional MAV and SUV max, and repeated ROVER measurements of MAV, SUV max, cSUV mean and cMVP mean were made. Bland-Altman and correlation analyses were performed to assess reproducibility and agreement. Our results showed that analyses of repeated ROVER measurements revealed MAV mean difference (D)=-0.03±0.53cc (95%CI(-0.22, 0.16)), lower limit of agreement (LLOA)=-1.07cc, and upper limit of agreement (ULOA)=1.01cc; SUV max D=0.00±0.00 with LOAs=000; cSUV mean D=-0.01±0.39 (95%CI(-0.15, 0.13)), LLOA=-0.76, and ULOA=0.75; cMVP mean D=-0.52±4.78cc (95%CI(-2.23, 1.23)), LLOA=-9.89cc, and ULOA=8.86cc. Comparisons between ROVER and manual measurements revealed volume D= -0.39±1.37cc (95%CI (-0.89, 0.11)), LLOA=-3.08cc, and ULOA=2.30cc; SUV max D=0.00±0.00 with LOAs=000. Mean percent increase in lesional SUV mean and MVP max followinq partial volume correction using ROVER was 84.25±36.00% and 84.45+35.94%, respectively. In conclusion, it is feasible to estimate MAV, SUV max, cSUV mean, and cMVP mean of spinal bone marrow metastases from 18F-FDG-PET/CT quickly and easily with good reproducibility via ROVER software. Partial volume correction is imperative, as uncorrected SUV mean and MVP mean are significantly underestimated, even for large lesions. This novel approach has great potential for practical, accurate, and precise combined structural-functional PET quantification of disease before and after therapeutic intervention.

Abx Advanced Biochemical Compounds Gmbh | Date: 2011-07-05

The invention relates to a device for the synthesis of radio-labeled compounds, which comprises a reaction vessel for reacting a precursor compound having protective groups with a radioactive isotope to obtain a first reaction product;

Sabri O.,University of Leipzig | Becker G.-A.,University of Leipzig | Meyer P.M.,University of Leipzig | Hesse S.,University of Leipzig | And 18 more authors.
NeuroImage | Year: 2015

α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[18F]Flubatine, formerly known as (-)-[18F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification. Dynamic PET emission recordings lasting 270min were acquired on an ECAT EXACT HR+ scanner in 12 healthy male non-smoking subjects (71.0±5.0years) following the intravenous injection of 353.7±9.4MBq of (-)-[18F]Flubatine. Individual magnetic resonance imaging (MRI) was performed for co-registration. PET frames were motion-corrected, before the kinetics in 29 brain regions were characterized using 1- and 2-tissue compartment models (1TCM, 2TCM). Given the low amounts of metabolite present in plasma, we tested arterial input functions with and without metabolite corrections. In addition, pixel-based graphical analysis (Logan plot) was used. The model's goodness of fit, with and without metabolite correction was assessed by Akaike's information criterion. Model parameters of interest were the total distribution volume VT (mL/cm3), and the binding potential BPND relative to the corpus callosum, which served as a reference region. The tracer proved to have high stability in vivo, with 90% of the plasma radioactivity remaining as untransformed parent compound at 90min, fast brain kinetics with rapid uptake and equilibration between free and receptor-bound tracer. Adequate fits of brain TACs were obtained with the 1TCM. VT could be reliably estimated within 90min for all regions investigated, and within 30min for low-binding regions such as the cerebral cortex.The rank order of VT by region corresponded well with the known distribution of α4β2* receptors (VT [thalamus] 27.4 ± 3.8, VT [putamen] 12.7±0.9, VT [frontal cortex] 10.0 ± 0.8, and VT [corpus callosum] 6.3 ± 0.8). The BPND, which is a parameter of α4β2* nAChR availability, was 3.41±0.79 for the thalamus, 1.04±0.25 for the putamen and 0.61±0.23 for the frontal cortex, indicating high specific tracer binding. Use of the arterial input function without metabolite correction resulted in a 10% underestimation in VT, and was without important biasing effects on BPND. © 2015 Elsevier Inc.

Manook A.,TU Munich | Yousefi B.H.,TU Munich | Willuweit A.,Evotec | Willuweit A.,ABX advanced biochemical compounds GmbH | And 17 more authors.
PLoS ONE | Year: 2012

In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [ 11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [ 11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [ 11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice. © 2012 Manook et al.

Gesim Gesellschaft Fuer Silizium Mikrosysteme Mbh and Abx Advanced Biochemical Compounds Gmbh | Date: 2011-06-20

The invention relates to a device for the preparation of radiochemical compounds. It is provided that the device comprises at least a reaction module, a dosing module, and a storage module, wherein; the reaction module has at least one reaction vessel having a closable opening through which substances needed for the preparation of a predetermined radiochemical compound can be introduced into the reaction vessel of the reaction module and through which the prepared radiochemical compound can be removed from the reaction vessel of the reaction module; the dosing module has at least one pipetting head which can be moved relative to the storage module and the reaction module and in x, y, and z directions and also has at least one dosing unit; and at least one reservoir for one of the substances needed for the preparation of the respective radiochemical compound is formed in the storage module.

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