SPET Imaging Research Articles

Employing Multiple Low-Dose PET Images (at Different Dose Levels) as Prior Knowledge to Predict Standard-Dose PET Images.

The existing deep learning-based denoising methods predicting standard-dose PET images (S-PET) from the low-dose versions (L-PET) solely rely on a single-dose level of PET images as the input of deep learning network. In this work, we exploited the prior knowledge in the form of multiple low-dose levels of PET images to estimate the S-PET images. To this end, a high-resolution ResNet architecture was utilized to predict S-PET images from 6 to 4% L-PET images. For the 6% L-PET imaging, two models were developed; the first and second models were trained using a single input of 6% L-PET and three inputs of 6%, 4%, and 2% L-PET as input to predict S-PET images, respectively. Similarly, for 4% L-PET imaging, a model was trained using a single input of 4% low-dose data, and a three-channel model was developed getting 4%, 3%, and 2% L-PET images. The performance of the four models was evaluated using structural similarity index (SSI), peak signal-to-noise ratio (PSNR), and root mean square error (RMSE) within the entire head regions and malignant lesions. The 4% multi-input model led to improved SSI and PSNR and a significant decrease in RMSE by 22.22% and 25.42% within the entire head region and malignant lesions, respectively. Furthermore, the 4% multi-input network remarkably decreased the lesions' SUVmean bias and SUVmax bias by 64.58% and 37.12% comparing to single-input network. In addition, the 6% multi-input network decreased the RMSE within the entire head region, within the lesions, lesions' SUVmean bias, and SUVmax bias by 37.5%, 39.58%, 86.99%, and 45.60%, respectively. This study demonstrated the significant benefits of using prior knowledge in the form of multiple L-PET images to predict S-PET images.

Sentinel node biopsy in endometrial cancer: an update

A review was conducted to update the recent published literature on sentinel lymph-node (SLN) procedures in endometrial cancer. A comprehensive literature search was performed in PubMed and Cochrane library, searching from English language publication of the last 10 years about sentinel lymph node (SLN) in endometrial cancer. Eligible studies had a sample size > 30 patients and reported at least the detection rate. Detection rate, bilateral mapping rate, sensitivity (SN), and negative predictive value (NPV) were evaluated. Different techniques were assessed both for detection rate and for bilateral mapping. A subgroup analysis on studies focused on SPET was performed. Forty studies were considered for the analysis (6162 patients). The overall detection rate of SLN mapping was 87.7% (95% CI 77.6–97.9%, range 62–100%). The pooled bilateral mapping rate was 59.9% (95% CI 43.2–76.6%, range 21–92%). The pooled SN resulted 98.3% (range: 50–100%) and the pooled NPV was 99.5% (range 86–100%). Cervical injection was the most used technique. Indocyanine green (ICG) and the combination of radiotracer/blue dye resulted in the highest SLN detection rates: 95% (95% CI 86–100%) and 90% (95% CI 79–100%) with cervical injection, respectively. ICG demonstrated the highest values of bilateral nodal mapping 75% (95% CI 60–91%) with cervical injection. Studies focused on SPET/CT showed a low/moderate correlation between SPET imaging and intraoperative findings. SLN mapping accurately predicts nodal status in women with endometrial cancer. Future prospective evaluation of prognosis/outcome is needed to define the impact of this technique for personalized therapy.

The practical value of technetium-99m-MIBI SPET to differentiate between ischemic and non-ischemic heart failure presenting with exertional dyspnea.

We aimed to differentiate ischemic heart failure (HF) from non-ischemic HF in patients presenting with non-acute onset exertional dyspnea using technetium-99m methoxyisobutylisonitrile gated single photon emission tomography ((99m)Tc-MIBI gSPET) imaging. One hundred and seventy nine consecutive patients with exertional dyspnea without concomitant chest pain referred to (99m)Tc-MIBI gSPET imaging were included in this study. All patients had a newly diagnosed HF with reduced ejection fraction (HFrEF). Imaging findings were compared between ischemic HF and non-ischemic HF groups. Of the 179 patients, 127 had ischemic HF and 52 had non-ischemic HF. There was no difference between ischemic and non-ischemic groups in terms of age, gender, body mass index, any smoking history, diabetes mellitus, history of hypertension and hyperlipidemia. Global dysfunction of left ventricle was more common in non-ischemic HF group than ischemic HF group (82.7% vs 41.7% respectively, P<0.001). Presence of severe (3+/4+) ischemia and large perfusion defect were higher in ischemic HF group compared to non-ischemic HF group (45.7% vs 15.4%, P<0.001 and 23.6% vs 3.8%, P=0.003, respectively). Summed stress score (SSS), summed rest score and summed difference score were higher in ischemic HF group compared to non-ischemic HF group (P<0.001, P<0.001, and P=0.021, respectively). In multivariate analysis, absence of global dysfunction (P<0.001, OR=10.338, 95%CI: 3.937-27.405) and SSS (P<0.001, OR=1.208, 95%CI: 1.090-1.339) were the independent predictors of ischemic HF. Absence of global dysfunction had 58.3% sensitivity and 86.7% specificity for diagnosis of ischemic HF at gSPET imaging in patients presenting with newly diagnosed HF and exertional dyspnea without concomitant chest pain (AUC=0.705, 95%CI: 0.632-0.771, P<0.001), whereas SSS>8 had 65.4% sensitivity and 75.0% specificity (AUC=0.732, 95%CI: 0.661-0.795, P<0.001). Absence of global dysfunction and SSS on SPET imaging were the independent predictors of ischemic etiology of HF presenting with dyspnea without concomitant chest pain. These findings had a low sensitivity, but acceptable specificity.

SPET–CT in thyroid cancer: a systematic review

The purpose of this study was to systematically review the utility of single-photon emission tomography–computed tomography (SPET–CT) fusion imaging in the investigation of thyroid cancer. We performed a systematic search of the world literature on radionuclide SPET–CT imaging of thyroid cancer using the medical databases Medline (OVID) and PubMed. The following search terms were used to identify relevant studies: (a) thyroid, combined with (b) SPECT/CT or SPECT–CT or SPET/CT or SPET–CT. The electronic searches returned citations for 1,189 potentially eligible articles and 98 abstracts were reviewed for relevance by two co-authors. Thirty-one peer-reviewed full articles reporting the utility, value and diagnostic performance of radioiodine SPET–CT for the imaging of well-differentiated thyroid cancer were selected. The quality of these studies was assessed using the quality assessment of diagnostic accuracy studies-2 tool. As there was heterogeneity in the studies, a systematic review analysis was conducted as our chosen research synthesis method. A total of 31 studies published between 2003 and 2014 report the utility of radioiodine SPET–CT. These studies uniformly found incremental diagnostic value of I-123 and I-131 SPET–CT over SPET and/or planar imaging. SPET–CT allows accurate characterization of radioiodine uptake in the neck and at distant sites, clarifies equivocal foci of radioactivity, improves specificity for disease, and evaluates benign physiological etiologies. Additional pilot uses of SPET–CT have been reported, e.g., for thyroid nodule evaluation, medullary thyroid cancer work-up, and investigation of lingual thyroid. Radioiodine SPET–CT fusion imaging of thyroid cancer has incremental utility, improving image interpretation as compared to planar and SPET imaging. It is likely to see more widespread application in the future.

An alternative approach to histopathological validation of PET imaging for radiation therapy image-guidance: A proof of concept

PurposeIn radiotherapy, PET images can be used to guide the delivery of selectively escalated doses to biologically relevant tumour subvolumes. Validation of PET for such applications requires demonstration of spatial coincidence between PET tracer uptake pattern and the histopathologically confirmed target. This study introduces a novel approach to histopathological validation of PET image segmentation for radiotherapy guidance. Methods and materialsSequential tissue sections from surgically excised whole-tumour specimens were used to acquire full 3D-sets of both histopathological images (microscopy) and PET tracer distribution images (autoradiography). After these datasets were accurately registered, a full 3D autoradiographic distribution of PET tracer was reconstructed and used to obtain synthetic PET images (sPET) by simulating the image deterioration induced by processes involved in PET image formation. To illustrate the method, sPET images were used in this study to investigate spatial coincidence between high FDG uptake areas and the distribution of viable tissue in two small animal tumour models. ResultsThe reconstructed 3D autoradiographic distribution of the PET tracer was spatially coherent, as indicated by the high average value of the normalised pixel-by-pixel correlation of intensities between successive slices (0.84±0.05 and 0.94±0.02). The loss of detail in the sPET images versus the 3D autoradiography was significant as indicated by Dice coefficient values corresponding to the two tumours (0 and 0.1 at 70% threshold). The maximum overlap between the FDG segmented volumes and the extent of the viable tissue as indicated by Dice coefficient values, was 0.8 for one tumour (for the image thresholded at 22% of max intensity) and 0.88 for the other (threshold of 14% of max intensity). ConclusionIt was demonstrated that the use of synthetic PET images for histopathological validation allows for bypassing a technically challenging and error-prone step of registering non-invasive PET images with histopathology.

123I]FP‐CIT SPET imaging in drug‐induced Parkinsonism

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug-induced parkinsonism (DIP). We performed [(123)I]FP-CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS-III was used to assess clinical severity. Twenty-six age- and sex-matched healthy subjects served as control group. Putamen [(123)I]FP-CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco-linguo-masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals.

Regional cerebral blood flow in childhood autism: a SPET study with SPM evaluation

To establish a link between rCBF assessed with Tc-ECD SPET and the clinical manifestation of the disease. We performed the study on 11 patients (five girls and six boys; mean age 11.2 years) displaying autistic behaviour and we compared their data with that of an age-matched reference group of eight normal children. A quantitative analysis of rCBF was performed calculating a perfusion index (PI) and an asymmetry index (AI) in each lobe. Images were analysed with statistical parametric mapping software, following the spatial normalization of SPET images for a standard brain. A statistically significant (P=0.003) global reduction of CBF was found in the group of autistic children (PI=1.07+/-0.07) when compared with the reference group (PI=1.25+/-0.12). Moreover, a significant difference was also observed for the right-to-left asymmetry of hemispheric perfusion between the control group and autistic patients (P=0.0085) with a right prevalence greater in autistic (2.90+/-1.68) with respect to normal children (1.12+/-0.49). Our data show a significant decrease of global cerebral perfusion in autistic children in comparison with their normal counterparts and the existence of left-hemispheric dysfunction, especially in the temporo-parietal areas devoted to language and the comprehension of music and sounds. We suggest that these abnormal areas are related to the cognitive impairment observed in autistic children, such as language deficits, impairment of cognitive development and object representation, and abnormal perception and responses to sensory stimuli. Tc-ECD SPET seems to be sensitive in revealing brain blood flow alterations and left-to-right asymmetries, when neuroradiological patterns are normal.

Comparative evaluation of 99mTc-depreotide and 201Tl chloride single photon emission tomography in the characterization of pulmonary lesions

To compare (99m)Tc-depreotide and (201)Tl chloride SPET in the characterization of pulmonary lesions. Fifty-seven pulmonary lesions from 33 patients suspected of malignancy in computed tomography, were assessed by (99m)Tc-depreotide and (201)Tl early and delayed SPET imaging. Images were visually assessed and the tumour-to-normal (T/N) lung activity ratio for early (ER) and delayed (DR) scans and the retention index (RI), were calculated in every lesion. A final diagnosis was reached for all lesions, based either on histology or prolonged clinical and radiological follow-up. Twenty-three lesions were characterized as malignant and 34 benign. In visual analysis, all malignant lesions accumulated both tracers resulting in sensitivity and negative predictive values of 100%. However, false positive interpretations resulted in a specificity of 64.7% and 67.6% for (99m)Tc-depreotide and (201)Tl, respectively. ER and DR of both agents and the RI of (99m)Tc-depreotide were significantly higher in malignant, compared to benign lesions. In defining thresholds of abnormality from ROC analysis, a significant increase in specificity was observed for both tracers in both scan phases (91.2% for all), as compared to visual analysis (P<0.01). There was no significant difference in the diagnostic performance between (99m)Tc-depreotide DR and (201)Tl DR, although the former provided the highest T/N ratio. This study demonstrates that (99m)Tc-depreotide and (201)Tl SPET are equally effective and may be useful in the non-invasive determination of lung malignancy. The specificity of both techniques is significantly improved by quantifying radiopharmaceutical accumulation in pulmonary lesions.

Comparative analysis of visual and semi-quantitative assessment of striatal [123I]FP-CIT-SPET binding in Parkinson's disease

We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.

Ce doped lanthanum tri-bromide SPET scanner for molecular imaging

The availability of LaBr 3:Ce crystals from St. Gobain has started various investigations in the field of medical imaging, in particular in PET, SPECT and Compton camera systems. At present LaBr 3:Ce crystals are available in a continuous shape covering up to 10×10 cm 2 with a thickness of 1 cm, in contrast, serious concerns are arising in pixellated manufacturing. With the aim of verifying the potentials introduced by LaBr 3:Ce for SPET imaging, two small γ cameras based on Anger camera principle have been assembled and imaging performances were compared. Two crystals of LaBr 3:Ce and NaI(Tl) with the same detection area (5×5 cm 2) and thickness of 5 and 1.5 mm, respectively were been integrally assembled with a H8500 Hamamatsu flat panel PMT. Through the thicker crystal, the LaBr 3:Ce camera showed superior imaging and detection performances at 140 keV compared with the NaI(Tl) one, with 0.9 mm FWHM intrinsic spatial resolution, 8% FWHM energy resolution and 80% intrinsic detection efficiency.

Technetium Tc 99m–Labeled Red Blood Cells in the Preoperative Diagnosis of Cavernous Hemangioma and Other Vascular Orbital Tumors

To evaluate technetium Tc 99m (99mTc) red blood cell scintigraphy as a diagnostic tool for orbital cavernous hemangioma and to differentiate between orbital masses on the basis of their vascularization. We performed 99mTc red blood cell scintigraphy on 23 patients (8 female and 15 male; mean age, 47 years) affected by an orbital mass previously revealed with computed tomography (CT) and magnetic resonance imaging (MRI) and suggesting cavernous hemangioma. In our diagnosis, we considered the orbital increase delayed uptake with the typical scintigraphic pattern known as perfusion blood pool mismatch. The patients underwent biopsy or surgical treatment with transconjunctival cryosurgical extraction when possible. Single-photon emission tomography (SPET) showed intense focal uptake in the orbit corresponding to radiologic findings in 11 patients who underwent surgical treatment and pathologic evaluation (9 cavernous hemangiomas, 1 hemangiopericytoma, and 1 lymphangioma). Clinical or histologic examination of the remaining 22 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the lacrimal gland, 1 astrocytoma, 1 ophthalmic vein thrombosis, and 1 orbital varix. The confirmation of the preoperative diagnosis by 99mTc red blood cell scintigraphy shows that this technique is a reliable tool for differentiating cavernous hemangiomas from other orbital masses (sensitivity, 100%; specificity, 86%) when ultrasound, CT, and MRI are not diagnostic. Unfortunately, 99mTc red blood cell scintigraphy results were positive in 1 patient with hemangiopericytoma and 1 patient with lymphangioma, which showed increased uptake in the lesion on SPET images because of the vascular nature of these tumors. Therefore, in these cases, the SPET images have to be integrated with data regarding clinical preoperative evaluation and CT scans or MRI studies. On the basis of our study, a complete diagnostic picture, CT scans or MRI studies, and scintigraphic patterns can establish the preoperative diagnosis of vascular orbital tumors such as cavernous hemangioma, adult-type lymphangioma, and hemangiopericytoma.

Diagnostic performance of 18F-FDG PET and ictal 99mTc-HMPAO SPET in pediatric temporal lobe epilepsy: Quantitative analysis by statistical parametric mapping, statistical probabilistic anatomical map, and subtraction ictal SPET

We investigated the diagnostic performance of 18F-FDG PET and ictal (99m)Tc-HMPAO SPET in pediatric temporal lobe epilepsy (TLE). Twenty-one pediatric TLE patients were enrolled in this study. Their diagnoses were confirmed by histology and post-surgical outcome (Engel class I or II). The patients' ages were 18 or younger (15+/-3 years). Of the 21 patients, 21 patients underwent 18F-FDG PET scan and 15 underwent ictal (99m)Tc-HMPAO SPET. Preoperative PET and/or ictal SPET images were reviewed by simple visual assessment and by statistical parametric mapping (SPM). Asymmetric indices (AI) were calculated using statistical probabilistic anatomical map (SPAM) on 18F-FDG PET. In nine patients who underwent both ictal and interictal SPET, SISCOM (subtraction ictal SPET coregistered to MR template) was performed. PET correctly localized epileptogenic zones in 20 of 21 (95%) by visual assessment. SPM analysis of PET correctly localized epileptogenic zones in 18 of 21 (86%). Ictal SPET correctly localized epileptogenic zones in 12 of 15 (80%) by visual assessment. SPM analysis of ictal SPET correctly localized epileptogenic zones in 12 of 15 (80%). SISCOM correctly localized 8 of 9 (89%), which was equal to that of visual assessment of ictal SPET. The AIs of the temporal lobes by PET were -15+/-8.4 in the left and 9.9+/-8.9 in the right TLE (normal control: -2.9+/-2.8), and correctly localized epileptogenic zones in all cases. As is found in adult TLE, PET and ictal SPET efficiently localized epileptogenic zones in pediatric TLE. SPM analysis of PET or ictal SPET could be used as an aid to visual assessment. Moreover, SISCOM was equal visual assessment of ictal SPET images in terms of lesion localizations.

SPET imaging of central muscarinic receptors with ( R, R)[ 123I]-I-QNB: methodological considerations

Investigations on the effect of normal healthy ageing on the muscarinic system have shown conflicting results. Also, in vivo determination of muscarinic receptor binding has been hampered by a lack of subtype selective ligands and differences in methods used for quantification of receptor densities. Recent in vitro and in vivo work with the muscarinic antagonist ( R, R)-I-QNB indicates this ligand has selectivity for m 1 and m 4 muscarinic receptor subtypes. Therefore, we used ( R, R)[ 123I]-I-QNB and single photon emission tomography to study brain m 1 and m 4 muscarinic receptors in 25 healthy female subjects (11 younger subjects, age range 26–32 years and 14 older subjects, age range 57–82 years). Our aims were to ascertain the viability of tracer administration and imaging within the same day, and to evaluate whether normalization to whole brain, compared to normalization to cerebellum, could alter the clinical interpretation of results. Images were analyzed using the simplified reference tissue model and by two ratio methods: normalization to whole brain and normalization to cerebellum. Significant correlations were observed between kinetic analysis and normalization to cerebellum, but not to whole brain. Both the kinetic analysis and normalization to cerebellum showed age-related reductions in muscarinic binding in frontal, orbitofrontal, and parietal regions. Normalization to whole brain, however, failed to detect age-related changes in any region. Here we show that, for this radiotracer, normalizing to a region of negligible specific binding (cerebellum) significantly improves sensitivity when compared to global normalization.

Synthesis and evaluation of iodinated TZTP-derivatives as potential radioligands for imaging of muscarinic M 2 receptors with SPET

A series of iodinated thiadiazolyltetrahydro-1-methyl-pyridine (TZTP) compounds was synthesized and evaluated in vitro and in vivo as potential radioligands for imaging of the muscarinic M 2 receptor subtype with SPET. One of these compounds, 5-(E)-iodopentenylthio-TZTP, has high in vitro affinity (K i = 4.9 nM) and moderate selectivity for the muscarinic M 2 receptor subtype. Although the uptake pattern in the biodistribution studies in rats is consistent with muscarinic M 2 receptor disribution, specific in vivo binding to these receptors could not be demonstrated. The usefulness of this tracer in human SPET imaging may therefore be limited.

Potential Biological Markers for Cerebrovascular Disease

Cerebrovascular diseases can causes cognitive impairment and dementia by loss of neurons and synaptic connections, destruction of axons, and demyelinization. Biological markers including genetic tests, brain imaging techniques, and biochemical assays in the CSF are valuable for the identification and quantification of cerebrovascular diseases. Genetic tests may be used to detect mutations that cause hereditary cerebral amyloid angiopathies or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Structural CT and MR imaging is routinely used to visualize and quantify infarcts and white-matter changes. Functional SPET and PET imaging can demonstrate focal and remote effects of vascular lesions on cerebral blood flow and metabolism. Biochemical imaging using proton MRS is a nonspecific marker for neuronal and axonal damage. Among biochemical markers in the CSF, tau protein, phospho-tau, and beta amyloid protein are helpful to differentiate vascular dementia from Alzheimer's disease.

Evaluation of cerebral neurotransmitter physiology and pathophysiology with pet and spet imaging modalities in animal models

Evaluation of cerebral neurotransmitter physiology and pathophysiology with pet and spet imaging modalities in animal models

Measurement of left ventricular volumes and ejection fraction by quantitative gated SPET, contrast ventriculography and magnetic resonance imaging: a meta-analysis.

All previous validation studies of quantitative gated single-photon emission tomography (QGS) have examined relatively few patients, and the accuracy of QGS thus remains uncertain. We performed a meta-analysis of data from 301 participants in ten studies that compared QGS using technetium-99m-labelled tracers with contrast left ventriculography (LVG), and from 112 participants in six studies that compared QGS with magnetic resonance imaging (MRI). Linear regression and Bland-Altman analyses were used to evaluate pooled data from individuals across the studies. The correlation between QGS and LVG for end-diastolic volume (EDV) (r=0.81, SEE=27 ml), end-systolic volume (ESV) (r=0.83, SEE=18 ml) and ejection fraction (EF) (r=0.79, SEE=8.3%) was good, as was that between QGS and MRI for EDV (r=0.87, SEE=34 ml), ESV (r=0.89, SEE=27 ml) and EF (r=0.88, SEE=7.2%). However, Bland-Altman plots indicated that LVG minus QGS differences for EDV generated a systematic and random error of 32+/-58 ml (mean+/-2SD), and that MRI minus QGS generated an error of 13+/-73 ml. In the subgroup of patients in whom ECG gating was set at eight intervals, QGS significantly underestimated EF by 7.6%+/-17.4% (mean+/-2SD) compared with LVG and by 6.3%+/-14.6% compared with MRI; no such underestimation was observed in the subgroup in whom ECG gating was set at 16 intervals. We conclude that in patients with ECG gating set at eight intervals, QGS systematically underestimates LV volumes and EF compared with both LVG and MRI. Since QGS also shows considerable variations around the systematic deviations, there remains uncertainty over whether an individual value determined with QGS approximates the true LV volumes and EF.

46. Assessment of clinical outcome in neuroendocrine tumours using functional volumes on SPET imaging and correlation with CT scan and clinical outcome

s of the 31st Annual Meeting of the British Nuclear Medicine Society, Manchester, UK, 29 April to 1 May 2003 - ONCOLOGY II

Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography

Normal aging is associated with a decrease in number and size of neurons, loss of synapses and neuronal branching and with a reduced functioning neurotransmitter systems, such as the serotonergic system. These structural and functional alterations have important impact on the behavioural, cognitive and affective status of the individual. With the introduction of functional brain imaging in veterinary medicine, the canine brain can be examined in vivo, evaluating changes in perfusion, metabolism and neurotransmitter systems. Since cognitive decline is recognised in the aging dog, it was our aim to investigate whether age related changes concerning cerebral perfusion and binding index of the selective 5-HT2A receptor ligand 123I-5-I-R91150 could be found in the canine brain. A group of twelve normal, aging dogs, older than 96 months, was compared to a normal reference group ( n=12), younger than 96 months. SPET images were obtained, using the radiopharmaceutical 99mTc- N, Nʺ-1,2-ethylene-diylbis- l-cysteine diethylester dihydrochloride ( 99mTc-ECD) for evaluation of the regional perfusion and the selective radioligand 123I-5-I-R91150 for visualization of the 5-HT2A receptor. Regional decrease of cerebral blood-flow was noted in the fronto- and temporocortical area and in the subcortical region. Age was negatively correlated with perfusion in the left and right fronto-cortical region. The binding index of the neuroreceptor radioligand was decreased in the fronto-cortical region, with a significant negative correlation with age in the right fronto-cortical area. No correlation was found between alteration of perfusion and binding index of the receptor ligand, suggesting that age related perfusion differences do not influence the binding of this radioligand. These results suggest that age related effects should be considered in functional canine brain imaging.

Comparative distribution of binding of the muscarinic receptor ligands pirenzepine, AF-DX 384, (R,R)-I-QNB and (R,S)-I-QNB to human brain

Quinuclidinyl benzilate (QNB) and its derivatives are being developed to investigate muscarinic receptor changes in vivo in Alzheimer's disease and dementia with Lewy bodies. This is the first study of [ 125I]-(R,R)-I-QNB and [ 125I]-(R,S)-I-QNB binding in vitro in human brain. We have compared the in vitro binding of the muscarinic ligands [ 3H]pirenzepine and [ 3H]AF-DX 384, which have selectivity for the M1 and M2/M4 receptor subtypes, respectively, to the binding of [ 125I]-(R,R)-I-QNB and [ 125I]-(R,S)-I-QNB. This will provide a guide to the interpretation of in vivo SPET images generated with [ 123I]-(R,R)-I-QNB and [ 123I]-(R,S)-I-QNB. Binding was investigated in striatum, globus pallidus, thalamus and cerebellum, and cingulate, insula, temporal and occipital cortical areas, which show different proportions of muscarinic receptor subtypes, in post-mortem brain from normal individuals. M1 receptors are of high density in cortex and striatum and are relatively low in the thalamus and cerebellum, while M4 receptors are mainly expressed in the striatum, and M2 receptors are most evident in the cerebellum and thalamus. [ 125I]-(R,R)-I-QNB and [ 125I]-(R,S)-I-QNB density distribution patterns were consistent with binding to both M1 and M4 receptors, with [ 125I]-(R,R)-I-QNB additionally binding to a non-cholinergic site not displaceable by atropine. This distribution can be exploited by in vivo imaging, developing ligands for both SPET and PET, to reveal muscarinic receptor changes in Alzheimer's disease and dementia with Lewy bodies during the disease process and following cholinergic therapy.