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Copenhagen, Denmark

Marner L.,Neurobiology Research Unit | Marner L.,Center for Integrated Molecular Brain Imaging | Frokjaer V.G.,Neurobiology Research Unit | Frokjaer V.G.,Center for Integrated Molecular Brain Imaging | And 12 more authors.
Neurobiology of Aging

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT 2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT 2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [ 18F]altanserin and [ 11C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([ 11C]DASB). Overall [ 18F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [ 11C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [ 11C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT 2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections. © 2012 Elsevier Inc.. Source

Greve D.N.,Massachusetts General Hospital | Greve D.N.,Harvard University | Svarer C.,Center for Integrated Molecular Brain Imaging | Fisher P.M.,Center for Integrated Molecular Brain Imaging | And 11 more authors.

Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([11C]SB207145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC. © 2013 Elsevier Inc. Source

Jensen T.K.,University of Southern Denmark | Holt P.,University of Southern Denmark | Gerke O.,PET and Cyclotron Unit | Gerke O.,University of Southern Denmark | And 5 more authors.
Scandinavian Journal of Urology and Nephrology

Objective: The treatment and prognosis of bladder cancer are based on the depth of primary tumour invasion and the presence of metastases. A highly accurate preoperative tumour, node, metastasis (TNM) staging is critical to proper patient management and treatment. This study retrospectively investigated the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed axial tomography ( 18F-FDG PET/CT) and magnetic resonance imaging (MRI) for preoperative N staging of bladder cancer. Material and methods. From June 2006 to January 2008, 48 consecutive patients diagnosed with bladder cancer were referred to preoperative staging including MRI and 18F-FDG PET/CT. Eighteen out of 48 patients underwent radical cystoprostatectomy including removal of lymph nodes for histology, and were included in the study. Values of 18F-FDG PET/CT and MRI for regional N staging were compared to histopathology findings, the gold standard. Results. 18F-FDG PET/CT and MRI were performed in 18 patients. The specificities for detection of lymph-node metastases for MRI and 18F-FDG PET/CT were 80% (n = 15) and 93.33% (n = 15), respectively. The negative predictive values were 80% (n = 15) and 87.5% (n = 16) for MRI and 18F-FDG PET/CT, respectively. The differences in specificity and negative predictive values were not statistically significant. Conclusions. No significant statistical difference between 18F-FDG PET/CT and MRI for preoperative N staging of urothelial bladder cancer was found in the study. However, the trend of the data indicates an advantage of 18F-FDG PET/CT over MRI. Larger prospective studies are needed to elucidate the role of 18F-FDG PET/CT in N staging of bladder cancer. © 2011 Informa Healthcare. Source

Gustafsson A.M.E.,Gothenburg University | Back T.,Gothenburg University | Elgqvist J.,Gothenburg University | Jacobsson L.,Gothenburg University | And 6 more authors.
Nuclear Medicine and Biology

Introduction: The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either 213Bi or 211At, both α-emitters, in an ovarian cancer model. Methods: One hundred female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected intraperitoneally with ~2.7 MBq of 213Bi-MX35 (n=20) or ~0.44 MBq of 211At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of 213Bi-MX35 (n=20) or 211At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected 213Bi-MX35 and 211At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16). Results: The animals injected with 213Bi-MX35 or 211At-MX35 2 weeks after cell inoculation had tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated reference group had a TFF of 0.20. The groups treated with 213Bi-MX35 or 211At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of 213Bi-MX35 and 211At-MX35 were very similar to each other and displayed no alarming activity levels in the investigated organs. Conclusions: Micrometastatic growth of an ovarian cancer cell line was reduced in nude mice after treatment with 213Bi-MX35or 211At-MX35. Treatment with 211At-MX35 provided a non-significantly better result for the chosen activity levels. The radiolabeled MX35 did not accumulate to a high extent in the investigated organs. No considerable signs of toxicity were observed. © 2012 Elsevier Inc. Source

Madsen K.,Neurobiology Research Unit | Marner L.,Neurobiology Research Unit | Haahr M.,Neurobiology Research Unit | Gillings N.,PET and Cyclotron Unit | Knudsen G.M.,Neurobiology Research Unit
Nuclear Medicine and Biology

Attention to tracer dose principles is crucial in positron emission tomography (PET), and deviations can induce serious errors. In this study, we devise a method for determining receptor occupancy of the mass dose of the radioligand itself and the in vivo affinity. Methods: The approach was used for [ 11C]SB207145, a new PET radioligand for imaging the cerebral 5-HT 4 receptors in humans. Test-retest PET studies with varying specific activities of [ 11C]SB207145 were conducted in seven healthy subjects, and the output parameter regional BP ND was modeled. Individual occupancy plots were first computed to estimate the mass dose that saturates 50% of receptors (ID 50), and subsequently, the maximal mass dose that can be injected (arbitrarily set at an occupancy <5%) was calculated. Scatchard plots were computed to estimate the in vivo K D. Results: Increasing the mass dose resulted in a decrease in BP ND, whilst the relative cerebellar uptake was unchanged. The ID 50 was 85.4±30.2 μg, and the upper mass dose limit was 4.5±1.6 μg, which does not require ultrahigh specific activity. The estimated in vivo K D was 2.8 nM (range 1.0-4.8), without any regional differences. Conclusion: The presented method for estimating the upper mass dose limit is suggested as part of validation of PET radioligands. © 2011 Elsevier Inc. Source

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