Evaluation of software tools for automated identification of neuroanatomical structures in quantitative ß-amyloid PET imaging to diagnose Alzheimer's disease.

INTRODUCTION: For regional quantification of nuclear brain imaging data, defining volumes of interest (VOIs) by hand is still the gold standard. As this procedure is time-consuming and operator-dependent, a variety of software tools for automated identification of neuroanatomical structures were developed. As the quality and performance of those tools are poorly investigated so far in analyzing amyloid PET data, we compared in this project four algorithms for automated VOI definition (HERMES Brass, two PMOD approaches, and FreeSurfer) against the conventional method. We systematically analyzed florbetaben brain PET and MRI data of ten patients with probable Alzheimer's dementia (AD) and ten age-matched healthy controls (HCs) collected in a previous clinical study. METHODS: VOIs were manually defined on the data as well as through the four automated workflows. Standardized uptake value ratios (SUVRs) with the cerebellar cortex as a reference region were obtained for each VOI. SUVR comparisons between ADs and HCs were carried out using Mann-Whitney-U tests, and effect sizes (Cohen's d) were calculated. SUVRs of automatically generated VOIs were correlated with SUVRs of conventionally derived VOIs (Pearson's tests). RESULTS: The composite neocortex SUVRs obtained by manually defined VOIs were significantly higher for ADs vs. HCs (p=0.010, d=1.53). This was also the case for the four tested automated approaches which achieved effect sizes of d=1.38 to d=1.62. SUVRs of automatically generated VOIs correlated significantly with those of the hand-drawn VOIs in a number of brain regions, with regional differences in the degree of these correlations. Best overall correlation was observed in the lateral temporal VOI for all tested software tools (r=0.82 to r=0.95, p<0.001). CONCLUSION: Automated VOI definition by the software tools tested has a great potential to substitute for the current standard procedure to manually define VOIs in ß-amyloid PET data analysis.

Lean body mass correction of standardized uptake value in simultaneous whole-body positron emission tomography and magnetic resonance imaging.

This study explores the possibility of using simultaneous positron emission tomography--magnetic resonance imaging (PET-MRI) to estimate the lean body mass (LBM) in order to obtain a standardized uptake value (SUV) which is less dependent on the patients' adiposity. This approach is compared to (1) the commonly-used method based on a predictive equation for LBM, and (2) to using an LBM derived from PET-CT data. It is hypothesized that an MRI-based correction of SUV provides a robust method due to the high soft-tissue contrast of MRI. A straightforward approach to calculate an MRI-derived LBM is presented. It is based on the fat and water images computed from the two-point Dixon MRI primarily used for attenuation correction in PET-MRI. From these images, a water fraction was obtained for each voxel. Averaging over the whole body yielded the weight-normalized LBM. Performance of the new approach in terms of reducing variations of (18)F-Fludeoxyglucose SUVs in brain and liver across 19 subjects was compared with results using predictive methods and PET-CT data to estimate the LBM. The MRI-based method reduced the coefficient of variation of SUVs in the brain by 41 ± 10% which is comparable to the reduction by the PET-CT method (35 ± 10%). The reduction of the predictive LBM method was 29 ± 8%. In the liver, the reduction was less clear, presumably due to other sources of variation. In conclusion, employing the Dixon data in simultaneous PET-MRI for calculation of lean body mass provides a brain SUV which is less dependent on patient adiposity. The reduced dependency is comparable to that obtained by CT and predictive equations. Therefore, it is more comparable across patients. The technique does not impose an overhead in measurement time and is straightforward to implement.

Robust, fully automatic delineation of the head contour by stereotactical normalization for attenuation correction according to Chang in dopamine transporter scintigraphy.

OBJECTIVES: Chang's method, the most widely used attenuation correction (AC) in brain single-photon emission computed tomography (SPECT), requires delineation of the outer contour of the head. Manual and automatic threshold-based methods are prone to errors due to variability of tracer uptake in the scalp. The present study proposes a new method for fully automated delineation of the head based on stereotactical normalization. The method was validated for SPECT with I-123-ioflupane. METHODS: The new method was compared to threshold-based delineation in 62 unselected patients who had received I-123-ioflupane SPECT at one of 3 centres. The impact on diagnostic power was tested for semi-quantitative analysis and visual reading of the SPECT images (six independent readers). RESULTS: The two delineation methods produced highly consistent semi-quantitative results. This was confirmed by receiver operating characteristic analyses in which the putamen specific-to-background ratio achieved highest area under the curve with negligible effect of the delineation method: 0.935 versus 0.938 for stereotactical normalization and threshold-based delineation, respectively. Visual interpretation of DVR images was also not affected by the delineation method. CONCLUSIONS: Delineation of the head contour by stereotactical normalization appears useful for Chang AC in I-123-ioflupane SPECT. It is robust and does not require user interaction. KEY POINTS: •Chang attenuation correction in brain SPECT requires delineation of the head contour. •Manual and threshold-based methods are prone to errors. •The study proposes a fully-automated method for delineation based on stereotactical normalization. •The method is shown to work reliably in I-123-ioflupane SPECT. •It might improve the workflow of I-123-ioflupane SPECT in everyday patient care.

CT-based attenuation correction in I-123-ioflupane SPECT.

PURPOSE: Attenuation correction (AC) based on low-dose computed tomography (CT) could be more accurate in brain single-photon emission computed tomography (SPECT) than the widely used Chang method, and, therefore, has the potential to improve both semi-quantitative analysis and visual image interpretation. The present study evaluated CT-based AC for dopamine transporter SPECT with I-123-ioflupane. MATERIALS AND METHODS: Sixty-two consecutive patients in whom I-123-ioflupane SPECT including low-dose CT had been performed were recruited retrospectively at 3 centres. For each patient, 3 different SPECT images were reconstructed: without AC, with Chang AC and with CT-based AC. Distribution volume ratio (DVR) images were obtained by scaling voxel intensities using the whole brain without striata as reference. For assessing the impact of AC on semi-quantitative analysis, specific-to-background ratios (SBR) in caudate and putamen were obtained by fully automated SPM8-based region of interest (ROI) analysis and tested for their diagnostic power using receiver-operator-characteristic (ROC) analysis. For assessing the impact of AC on visual image reading, screenshots of stereotactically normalized DVR images presented in randomized order were interpreted independently by two raters at each centre. RESULTS: CT-based AC resulted in intermediate SBRs about half way between no AC and Chang. Maximum area under the ROC curve was achieved by the putamen SBR, with negligible impact of AC (0.924, 0.935 and 0.938 for no, CT-based and Chang AC). Diagnostic accuracy of visual interpretation also did not depend on AC. CONCLUSIONS: The impact of CT-based versus Chang AC on the interpretation of I-123-ioflupane SPECT is negligible. Therefore, CT-based AC cannot be recommended for routine use in clinical patient care, not least because of the additional radiation exposure.

Altered serotonin transporter availability in patients with multiple sclerosis.

PURPOSE: Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET. METHODS: Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [(11)C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability. RESULTS: Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p = 0.05). CONCLUSION: Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS.

PET quantification of 18F-florbetaben binding to ß-amyloid deposits in human brains.

UNLABELLED: (18)F-florbetaben is a novel (18)F-labeled tracer for PET imaging of ß-amyloid deposits in the human brain. We evaluated the kinetic model-based approaches to the quantification of ß-amyloid binding in the brain from dynamic PET data. The validity of the practically useful tissue ratio was also evaluated against the model-based parameters. METHODS: (18)F-florbetaben PET imaging was performed with concurrent multiple arterial sampling after tracer injection (300 MBq) in 10 Alzheimer disease (AD) patients and 10 age-matched healthy controls. Regional brain-tissue time-activity curves for 90 min were analyzed by a 1-tissue-compartment model and a 2-tissue-compartment model (2TCM) with metabolite-corrected plasma data estimating the specific distribution volume (VS) and distribution volume ratio (DVR [2TCM]) and a multilinear reference tissue model estimating DVR (DVR [MRTM]) using the cerebellar cortex as the reference tissue. Target-to-reference tissue standardized uptake value ratios (SUVRs) at 70-90 min were also calculated. RESULTS: All brain regions required 2TCM to describe the time-activity curves. All ß-amyloid binding parameters in the cerebral cortex (VS, DVR [2TCM], DVR [MRTM], and SUVR) were significantly increased in AD patients (P < 0.05), and there were significant linear correlations among these parameters (r(2) > 0.83). Effect sizes in group discrimination between 8 ß-amyloid-positive AD scans and 9 ß-amyloid-negative healthy control scans for all binding parameters were excellent, being largest for DVR (2TCM) (4.22) and smallest for VS (3.25) and intermediate and the same for DVR (MRTM) and SUVR (4.03). CONCLUSION: These results suggest that compartment kinetic model-based quantification of ß-amyloid binding from (18)F-florbetaben PET data is feasible and that all ß-amyloid binding parameters including SUVR are excellent in discriminating between ß-amyloid-positive and -negative scans.

Imaging of the brain serotonin transporters (SERT) with 18F-labelled fluoromethyl-McN5652 and PET in humans.

PURPOSE: [(11)C]DASB is currently the most frequently used highly selective radiotracer for visualization and quantification of central SERT. Its use, however, is hampered by the short half-life of (11)C, the moderate cortical test-retest reliability, and the lack of quantifying endogenous serotonin. Labelling with (18)F allows in principle longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly use the new highly SERT-selective (18)F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[(18)F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification. METHODS: The PET data from five healthy volunteers (three men, two women, age 39 ± 10 years) coregistered with individual MRI scans were semiquantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and total distribution volumes (V (T)) were calculated using a two-tissue compartment model and arterial input function measurements were corrected for metabolite/plasma data. Standardized uptake region-to-cerebellum ratios as a measure of specific radiotracer accumulation were compared with those of a [(11)C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years). RESULTS: The two-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume (V (T)) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V (T) <10%). Compared with [(11)C]DASB PET, there was a tendency to lower mean uptake values in (+)-[(18)F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[(18)F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans. CONCLUSION: The results showed that (+)-[(18)F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of (18)F, the widespread use within a satellite concept seems feasible.

Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database.

PURPOSE: Multi-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example. METHODS: A framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device. RESULTS: A total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images. CONCLUSION: A framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Dissociating behavioral disorders in early dementia-An FDG-PET study.

Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.

Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database.

PURPOSE: A joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [(123)I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved. METHODS: (123)I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the "Southampton" methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV). RESULTS: The relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69-89%, ACSC range 87-116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001). CONCLUSION: A satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.

Decreased cerebral α4ß2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography.

PURPOSE: Postmortem studies indicate a loss of nicotinic acetylcholine receptor (nAChRs) in Alzheimer's disease (AD). In order to establish whether these changes in the cholinergic system occur at an early stage of AD, we carried out positron emission tomography (PET) with a specific radioligand for the α4ß2* nicotinic acetylcholine receptor (α4ß2* nAChR) in patients with mild to moderate AD and in patients with amnestic mild cognitive impairment (MCI), who have a high risk to progress to AD. METHODS: Nine patients with moderate AD, eight patients with MCI and seven age-matched healthy controls underwent 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BP(ND)) of 2-[(18)F]FA-85380 was calculated using either the corpus callosum or the cerebellum as reference regions. PET data were analysed by region of interest analysis and by voxel-based analysis. RESULTS: Both patients with AD and MCI showed a significant reduction in 2-[(18)F]FA-85380 BP(ND) in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[(18)F]FA-85380 BP(ND) correlated with the severity of cognitive impairment. Only MCI patients that converted to AD in the later course (n = 5) had a reduction in 2-[(18)F]FA-85380 BP(ND). CONCLUSION: 2-[(18)F]FA-85380 PET appears to be a sensitive and feasible tool for the detection of a reduction in α4ß2* nAChRs which seems to be an early event in AD. In addition, 2-[(18)F]FA-85380 PET might give prognostic information about a conversion from MCI to AD.

Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study.

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Measurement of the alpha4beta2* nicotinic acetylcholine receptor ligand 2-[(18)F]Fluoro-A-85380 and its metabolites in human blood during PET investigation: a methodological study.

2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) is a new radioligand for noninvasive imaging of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET) in human brain. In most cases, quantification of 2-[(18)F]FA receptor binding involves measurement of free nonmetabolized radioligand concentration in blood. This requires an efficient and reliable method to separate radioactive metabolites from the parent compound. In the present study, three analytical methods, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) have been tested. Reversed-phase TLC of deproteinized aqueous samples of plasma provides good estimates of 2-[(18)F]FA and its metabolites. However, because of the decreased radioactivity in plasma samples, this method can be used in humans over the first 2 h after radioligand injection only. Reliable quantification of the parent radioligand and its main metabolites was obtained using reversed-phase HPLC, followed by counting of eluted fractions in a well gamma counter. Three main and five minor metabolites of 2-[(18)F]FA were detected in human blood using this method. On average, the unchanged 2-[(18)F]FA fraction in plasma of healthy volunteers measured at 14, 60, 120, 240 and 420 min after radioligand injection was 87.3+/-2.2%, 74.4+/-3%, 68.8+/-5%, 62.3+/-8% and 61.0+/-8%, respectively. In patients with neurodegenerative disorders, the values corresponding to the three last time points were significantly lower. The fraction of nonmetabolized 2-[(18)F]FA in plasma determined using SPE did not differ significantly from that obtained by HPLC (+gamma counting) (n=73, r=.95). Since SPE is less time-consuming than HPLC and provides comparable results, we conclude that SPE appears to be the most suitable method for measurement of 2-[(18)F]FA parent fraction during PET investigations.

Different mechanisms for changes in glucose uptake of the right and left ventricular myocardium in pulmonary hypertension.

UNLABELLED: In patients with pulmonary hypertension (PH) the right ventricular (RV)-to-left ventricular (LV) ratio of fatty acid uptake is reduced. In animal studies, such a finding was combined with an increased glucose uptake in RV myocardium. The aim of this study was to measure the metabolic rates of glucose uptake for the RV and LV myocardium in patients in relationship to parameters of RV and LV function. METHODS: Thirty patients with PH underwent PET with (18)F-FDG and SPECT with (99m)Tc-tetrofosmine. The metabolic rate of glucose uptake was determined for RV and LV myocardium using the method of Patlak. A right heart catheter, thermodilution, and Doppler sonography were used to characterize RV and LV function. From these methods, the stroke work of both ventricles and the RV Tei index were calculated. RESULTS: RV-to-LV ratios of (18)F-FDG-uptake increased with rising pulmonary arteriolar resistance (PAR). With increasing PAR, the metabolic rate of glucose uptake of the left ventricle decreased (r = -0.547; P < 0.01) together with LV stroke work (r = -0.838; P < 0.001). The metabolic rate of glucose uptake of the right ventricle, however, correlated neither with RV stroke work (r = 0.124) nor with PAR (r = 0.189) but with the Tei index (r = 0.78; P < 0.001). CONCLUSION: Increasing right-to-left ratios of glucose uptake with an increasing pressure load in the right ventricle in PH are caused mainly by a significant reduction in the LV metabolic rate of glucose uptake. This is obviously due to a reduced energy demand of the LV myocardium caused by reduced stroke work. An increased metabolic rate of glucose uptake in the right ventricle presumably indicates RV impairment, correlating with the Tei index, which is an established prognostic parameter for cardiac dysfunction and poor survival.

Investigating dopaminergic neurotransmission with 123I-FP-CIT SPECT: comparability of modern SPECT systems.

UNLABELLED: With (123)I-labeled N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl)nortropane (FP-CIT) SPECT increasingly gaining access into routine patient care, the comparability of the results of different SPECT systems in the quantification of receptor binding is important for accurate clinical decision making and the translation of imaging results between institutions (e.g., as part of multicenter therapy trials). METHODS: In a series of studies using phantoms (containing target cylinders of 2- and 2.8-cm diameter) and (123)I-FP-CIT patient studies (n = 49), we compared target-to-background (T/BG) and (123)I-FP-CIT striatal uptake ratios recovered by a conventional triple-head SPECT system and a dedicated high-resolution brain SPECT system. All patient studies were acquired on both SPECT systems successively (<15-min interscan gap) using a single-injection protocol (group A [n = 20] was first scanned on the triple-head SPECT system, and group B [n = 29] was first scanned on the dedicated brain SPECT system). RESULTS: In phantom studies, the T/BG ratios recovered by both systems correlated strongly with the true T/BG ratios (R(2) > 0.96), with the linear regression slopes being 0.86-1.17 and 0.41-0.52 (less steep for smaller target size and lower T/BG ratios) for the dedicated brain SPECT and the triple-head SPECT system, respectively. Although both systems yielded markedly different results, they showed a high linear correlation with each other (R(2) > 0.95, no significant effect from target size). In (123)I-FP-CIT patient studies, a similar linear intersystem correlation was found (R(2) [A/B] = 0.79/0.80, 0.52/0.68, and 0.83/0.85 for the uptake ratios of the striatum, caudate, and putamen, respectively, to the occipital reference region). CONCLUSION: A linear transformation of striatal uptake ratios between different SPECT systems appears to be achievable for ligands such as (123)I-FP-CIT. An evaluation is needed of whether the present method can do this with sufficient accuracy for clinical purposes or whether methodologic adaptations are necessary. Proper study timing has to be ensured.

[18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors.

The present study compares the uptake of [(18)F]Fluoroazomycinarabinofuranoside ((18)FAZA), a recently developed hypoxia tracer for PET imaging of tissue hypoxia, with an established tracer [(18)F]Fluoromisonidazole ((18)FMISO) both in vitro, using Walker 256 rat carcinosarcoma cells, and in vivo in experimental rat tumors eleven to twelve days after tumor cell implantation. In vitro studies indicated that hypoxia-selective uptake of both (18)FAZA and (18)FMISO in tumor cells, 20 and 100 minutes post-incubation was of the same magnitude (20 min: 1.24 +/- 0.4% ((18)FAZA); 1.19 +/- 0.7% ((18)FMISO); 100 min: 3.6 +/- 1.6% ((18)FAZA); 3.3 +/- 1.7% ((18)FMISO)). PET imaging reflected a similar radiotracer distribution in rat tumors for (18)FAZA and (18)FMISO one h after radiotracer injection. The concentration of (18)FAZA in the tumors as measured by PET, however, was lower in comparison to (18)FMISO (SUV(FAZA) = 0.61 +/- 0.2 vs. SUV(FMISO) = 0.92 +/- 0.3, p < 0.05) although the tumor to muscle ratios for (18)FAZA and (18)FMISO did not differ in the PET images that were obtained after one h (SUV(FAZA) = 2.5 +/- 0.5 vs. SUV(FMISO) = 2.9 +/- 0.7). A comparison of PET data three h post-injection (SUV(FAZA) = 3.0 +/- 0.5 vs. SUV(FMISO) = 4.6 +/- 1.8, p < 0.05) demonstrated a lower (18)FAZA uptake that indicates a lower sensitivity of (18)FAZA in comparison to (18)FMISO in detecting hypoxic regions at a longer time in this animal model. However, these data also show a faster elimination of (18)FAZA from blood, viscera and muscle tissue, via the renal system. This advantage of a faster reduction of unspecific binding, in light of similar or marginally lower tumor uptake, warrants further investigation of (18)FAZA as a marker of regional hypoxia in tumors.

Is correction for age necessary in neuroimaging studies of the central serotonin transporter?

The central neurotransmitter serotonin plays a major role in a number of neuropsychiatric disorders. However, results from post-mortem and in vivo neuroimaging studies of the influence of age on the number of presynaptic serotonin transporters (SERT) are controversial. To provide further evidence of relevance for this ongoing discussion, SERT were imaged in 22 persons without neuropsychiatric impairment using [(123)I]2beta-carbomethoxy-3beta-(iodophenyl)tropane ([(123)I]beta-CIT) and high-resolution single-photon emission tomography (SPET). The SPET analysis method was based on magnetic resonance image co-registration in order to quantify SERT with acceptable inter- and intra-observer variability. Using this technique, we found a significant age-related decline in the thalamic/hypothalamic and midbrain/upper brainstem SERT density, which was more pronounced than that previously reported in the literature. From these results we conclude that age-related changes in SERT density need to be considered in future clinical studies.