Single-photon Emission Tomography Studies Research Articles

Nuclear medicine: workplace monitoring and internal occupational exposure during a ventilation/perfusion single-photon emission tomography.

The administration of 99mTc-HDP to diagnose pulmonary thromboembolisms leads to the presence of 99mTc in the environment of a nuclear medicine department, which could pose a potential risk of internal contamination to medical staff. Therefore, air samples from the administration room, gamma camera room and corridor of such a department were taken for the purpose of performing a workplace monitoring program of the medical centre under study, with maximum activity values of 640 ± 30kBq/m3, 1.5 ± 0.1kBq/m3 and 54 ± 3kBq/m3, respectively, being obtained. These results correspond to committed effective doses received by exposed employees, via inhalation, when one ventilation/perfusion single-photon emission tomography study was performed, of 0.7μSv, 0.004μSv and 0.2μSv, respectively. As inhalation is the employees' main exposure pathway to radio-aerosols, the internal dose of the nuclear medicine department's medical staff was also evaluated via urine bioassay measurements. Nuclear medicine nurses showed the highest 99mTc activity in 24-h urine samples (2100 ± 130Bq/day), resulting in a committed effective dose of 21μSv for each diagnostic study performed. Even so, the performance of ventilation/perfusion diagnostic studies did not constitute a substantial radiological risk since the annual dose limit for exposed employees was not exceeded.

Nuclear medicine for the investigation of canine behavioral disorders

The aim of this review was to report the current literature concerning the use of nuclear imaging modalities for the investigation of the neurobiology of canine behavioral disorders. The conventionally used nuclear medicine modalities are positron emission tomography and single photon emission (computed) tomography. At this moment, information is scarce about their application in veterinary behavioral medicine and only present for single photon emission tomography studies in dogs, mainly using 99mTc-ethyl cysteinate dimer to assess brain perfusion (and indirectly neuronal function) and 123I-5-I-R91150 to evaluate the 5-hydroxytryptamine-2A receptor binding. Current results suggest that functional nuclear imaging provides useful noninvasive in vivo information about the neurobiology and therapeutic evaluation of canine behavioral disorders. Due to striking similarities with neurobiological alterations in human disorders, the dog also represents an interesting natural animal model for human neuropsychiatric diseases.

EPA-0409 – Depression, incidental lewy body disease and pure psychiatric presentation of the lewy body disease

Introduction Parkinson's disease (PD), PD dementia (PDD) and dementia with Lewy body (DLB), collectively termed Lewy body disease (LBD), characterize an array of emotional, neurobehavioral and cognitive symptoms. Pure psychiatric presentation (PPP) of LBD is the fourth subtype of LBD in which psychiatric symptoms lasted for many years in the absence of neurological disturbance. Aims The aim of this study is to localize the PPP and its clinical characteristics in subjects with low uptake of myocardial metaiodobenzylguanidine (MIBG) study. Methods Sixty MIBG-verified patients (28 women and 32 men) were grouped into three psychiatric pictures; depression (group D: 27 patients), isolated visual hallucinations (group V: 16 patients) and psychotic picture (group P: 17 patients). Fifty six cases were examined with cerebral single photon emission tomography study. Thirty-seven cases had hypoperfusion regions and 19 cases showed no abnormality. Final diagnoses of PD, PDD, DLB and PPP were evaluated with an aid of DSM-IV-TR, UPDRS part III, the Hoehn and Yahr Scale, MMSE and the movement disorder society task force diagnostic criteria. Results Three clusters, PDD and Group P, DLB and Group V, and Group D and PPP-PD were found significantly with correspondence analysis. UPDRS average score showed negative correlation with average MMSE scores. All patients with PPP and majority of patients with PD featured depression. Conclusions PPP subjects are considered to be incidental LBD or depression of pre-motor PD. Psychotic parkinsonian features contributed highly to dementia of LBD, and visual hallucination was closely associated with DLB.

Imaging the Role of GABA in Movement Disorders

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. This paper reviews the current knowledge derived from positron emission tomography and single photon emission tomography studies quantifying GABAA receptor binding in movement disorders of extrapyramidal origin, focusing on essential tremor (ET), Parkinsonism (idiopathic PD and atypical parkinsonian syndromes), dystonia, and Huntington's disease (HD). In ET, there is evidence to suggest a specific disturbance at the level of the GABAA receptor and impairment of GABAergic inhibition to be a driving force for the development of rhythmic overactivity in cerebello-thalamo-cortical networks. In dystonia, GABAA receptor binding studies have been relevant for unraveling pathophysiological mechanisms causing sensorimotor disinhibition leading to dystonic movements. The role of GABA in idiopathic PD and atypical parkinsonian syndromes is less clear, despite the fact that GABAA receptors are expressed on virtually all striatal neurons and that GABA exerts important inhibitory influences upon basal outflow pathways. In HD, reductions of GABAA receptor have been reported in the basal ganglia but were found to be less extensive compared with concomitant metabolic reductions.

Investigation of blood perfusion and metabolic activity of brain tumours in adults by using 99mTc-methoxyisobutylisonitrile

(i) To examine blood perfusion and metabolic activity of various brain tumours using radionuclide cerebral angiography (RCA) and single-photon emission tomography (SPET) after a single dose of Tc-methoxyisobutylisonitrile (MIBI). (ii) To examine if the inclusion of RCA can improve insight into the relative contribution of tumour perfusion to the uptake of MIBI shown by SPET, and to improve evaluation of tumour biology. (iii) To determine the value and the roles of MIBI in the management of brain tumour patients. Fifty adult patients (38 male, 12 female) with a total of 56 intracranial space-occupying lesions have been included prospectively, 37 of which were newly diagnosed and the remaining with signs of recurrence/rest of earlier resected and irradiated brain tumours. The control group consisted of nine volunteers with no evidence of organic cerebral disease. Scintigraphic examination consisted of a dynamic first-pass study lasting 60 s (3 s/frame) and two SPET studies (60 projections each, 25 s/projection), starting 15 min and 2 h after intravenous injection of MIBI. Regions of interest of the tumour and normal brain tissue were drawn on RCA and both early and delayed SPET slices. The following tumour/brain activity ratios have been calculated: (i) tumour perfusion index (P); (ii) early uptake index (E); (iii) delayed uptake index (D); and(iv) retention index (R). Analogous indices have been calculated from the same examinations performed in controls, reflecting maximal physiologic regional variations of perfusion and uptake in brain tissue. Mean P of various brain tumours (low-grade gliomas 0.98, anaplastic gliomas 1.14, glioblastoma multiforme 1.20, metastases 1.09, lymphomas 1.08) differ little from each other and do not exceed maximal physiologic regional variations of cerebral perfusion (1.33), with the exception of meningioma (1.87, F=2.83, P=0.015). The receiver operating characteristics curve analysis of P showed that for the cut-off value of 1.45 the sensitivity for distinguishing meningioma from other tumours is 75%, specificity 87%, positive predictive value 33% and negative predictive value 97%. Mean E of malignant brain tumours (8.3, n=31, 23 primary, eight secondary), except anaplastic gliomas (3.5, n=5), differed significantly (P=0.02) from those of benign gliomas (3, n=9) but not from that of meningioma (11.9, n=4). The cut-off value for distinguishing malignant from benign lesions on the basis of E set at 4.8 resulted in sensitivity 67%, specificity 75%, accuracy 70%, positive predictive value 80% and negative predictive value 60%. D and R showed tendency of wash-out of MIBI from meningiomas, but otherwise did not improve the results substantially. Integrated results of RCA and SPET with Tc-MIBI indicate that blood perfusion, blood-tumour barrier permeability and metabolic activity of the tumour are all very important for the resultant uptake shown by SPET. If the perfusion index is less than 1.45, then meningioma can be ruled out. Early SPET is recommendable for distinguishing glioblastoma from low-grade gliomas, as a complement to standard magnetic resonance imaging and/or computed tomography.

Does intravenous Δ9-tetrahydrocannabinol increase dopamine release? A SPET study

Intravenous (IV) Δ9-tetrahydrocannabinol (THC) induces transient psychotic symptoms in healthy subjects and in schizophrenic patients, but the psychotomimetic mechanism is unknown. One possibility is that THC stimulates dopamine (DA) release in the striatum. In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5 mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30 min following IV THC. There were no significant differences in binding index in the caudate or putamen under THC compared to placebo conditions. Positive psychotic symptoms and DA release were unrelated. THC did not lead to a significant increase in DA release even though the dose was sufficient for participants to have psychotic symptoms. These findings do not support a central role for striatal DA in THC-elicited psychosis.

Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin sisters, and healthy women: a SPET study

BackgroundBulimia Nervosa (BN) is believed to be caused by an interaction of genetic and environmental factors. Previous studies support the existence of a bulimia-related endophenotype as well as disturbances in serotonin (5-HT) transmission. We studied serotonin transporter (SERT) binding in BN, and to investigate the possibility of a SERT-related endophenotype for BN, did this in a sample of female twins. We hypothesized clearly reduced SERT binding in BN women as opposed to healthy women, and intermediate SERT binding in unaffected co-twins.MethodsWe studied 13 female twins with BN (9 with purging and 4 with non-purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients and 19 women from 10 healthy twin pairs. [123I]ADAM, a selective SERT radioligand for single photon emission tomography (SPET) imaging, was used to assess SERT availability in the midbrain and the thalamus.ResultsNo differences in SERT binding were evident when comparing the BN women, their unaffected co-twins and the healthy controls (p = 0.14). The healthy sisters of the BN patients and the healthy control women had similar SERT binding in both brain regions. In a post hoc subgroup analysis, the purging bulimics had higher SERT binding than the healthy women in the midbrain (p = 0.03), but not in the thalamus.ConclusionOur finding of increased SERT binding in the midbrain in the purging BN women raises the possibility that this subgroup of bulimics might differ in serotonergic function from the non-purging ones. The similarity of the unaffected co-twins and the healthy controls doesn't support our initial assumption of a SERT-related endophenotype for BN. Due to the small sample size, our results need to be interpreted with caution and verified in a larger sample.

Estrogen Therapy and brain muscarinic receptor density in healthy females: A SPET study

Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer's disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and ( R, R)[ 123I]-I-QNB, a novel ligand with high affinity for m 1/m 4 muscarinic receptors, to examine the effect of long-term ET and age on brain m 1/m 4 receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n = 2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, ( R, R)[ 123I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels.

Functional correlates of Apolipoprotein E genotype in Frontotemporal Lobar Degeneration

BackgroundIt has been recently demonstrated that in Frontotemporal Lobar Degeneration (FTLD) memory deficits at presentation are commoner than previously thought. Apolipoprotein E (ApoE) genotype, the major genetic risk factor in sporadic late-onset Alzheimer Disease (AD), modulates cerebral perfusion in late middle-age cognitively normal subjects. ApoE ε4 homozygous have reduced glucose metabolism in the same regions involved in AD.The aim of this study was to determine whether ApoE genotype might play a key-role in influencing the cerebral functional pattern as well as the degree of memory deficits in FTLD patients.MethodsFifty-two unrelated FTLD patients entered the study and underwent a somatic and neurological evaluation, laboratory examinations, a brain structural imaging study, and a brain functional Single Photon Emission Tomography study. ApoE genotype was determined.ResultsApoE genotype influenced both clinical and functional features in FTLD. ApoE ε4-carriers were more impaired in long-term memory function (ApoE ε4 vs. ApoE non ε4, 6.3 ± 3.9 vs. 10.1 ± 4.2, p = 0.004) and more hypoperfused in uncus and parahippocampal regions (x,y,z = 38,-6,-20, T = 2.82, cluster size = 100 voxels; -32,-12,-28, T= 2.77, cluster size = 40 voxels).ConclusionThe present findings support the view that ApoE genotype might be considered a disease-modifying factor in FTLD, thus contributing to define a specific clinical presentation, and might be of relevance for pharmacological approaches.

Mapping of the cardiac sympathetic nervous system by single photon emission tomography with technetium-99m-labelled fluorobenzylpiperidine derivative (99mTc-FBPBAT): result of a feasibility study in a porcine model and an initial dosimetric estimation in humans

Positron emission tomography (PET) and single photon emission tomography (SPET) offer the most promising tools for the in-vivo assessment of the cardiac autonomic nervous system in humans. However, the clinical application of PET and SPET on a routine basis is severely limited by the lack of widely available selective radiotracers. Technetium-99m-labelled 4-fluorobenzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2-mercapto-2-methyl-propylamino)-piperidine (99mTc-FBPBAT) is a recently developed radiotracer which exhibited marked adrenergic affinity in previous investigations in vascular smooth muscle cells and cardiac myocytes, and in rats. In this study, we have verified these findings in a porcine model, and evaluated the potential of SPET with 99mTc-FBPBAT to assess the adrenergic nervous system of the heart. Using a SPET camera, scintigraphic evaluations were carried out in pigs following intravenous injection of 99mTc-FBPBAT. The specificity of the cardiac uptake was determined by pharmacological intervention, using alpha- and beta-adrenoceptor antagonists and adrenergic re-uptake blocker. Whole-body kinetic and radiation absorbed doses were estimated from whole-body scintigraphies in two healthy volunteers. 99mTc-FBPBAT-SPET demonstrated a homogeneous distribution of radioactivity in myocardium of pigs and in humans. The cardiac uptake was specifically suppressed by previous treatment of the animals with metoprolol and prazosin, and was displaceable by norepinephrine. In contrast, the inhibition of radioactivity uptake into the heart was less pronounced after pretreatment with desipramine. The peak radioactivity in blood was determined after 1.5-2 min, followed by a plateau of nearly constant radioactivity from 25-30 min onwards. Within 6 h, more than 35% of the injected activity was excreted in the urine. The effective dose according to International Commission on Radiological Protection Publication 60 (ICRP 60) was 0.0064 mSv.MBq-1 for adults. In view of these findings, we conclude that the myocardial uptake of 99mTc-FBPBAT reflects the sympathetic adrenergic nervous system of the heart. The effective dose estimated indicates that the clinical use of 99mTc-FBPBAT results in an acceptable radiation dose in humans. Despite the relatively high radioactivity uptake into the lung and liver, 99mTc-FBPBAT appears to be the first promising Tc-based radiotracer for scintigraphic assessment of the cardiac adrenergic system. This result encourages further development of Tc-based agents for routine SPET studies in humans.

Imaging early-stage corticobasal degeneration with [99mTc]TRODAT-1 SPET.

The aim of this study was to investigate the nigrostriatal dopaminergic function in patients with corticobasal degeneration (CBD) using [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]-[99mTc]technetium ([99mTc]TRODAT-1) brain single-photon emission tomography (SPET). Five patients with probable CBD, 10 age- and duration-matched patients with idiopathic Parkinson's disease (IPD) and 10 age-matched healthy volunteers completed the SPET study. The images were obtained 4 h after intravenous injection of 925 MBq of [99mTc]TRODAT-1. Using a magnetic resonance imaging atlas of the striatum, the ratios of specific striatal binding to non-specific occipital binding were calculated. Clinical analysis showed that the CBD patients obtained significantly higher scores on the Unified Parkinson's Disease Rating Scale and a significantly worse score for activities of daily living. In the CBD and IPD groups, striatum-occipital/occipital, caudate nucleus-occipital/occipital and putamen-occipital/occipital ratios decreased significantly relative to those of healthy subjects. No statistical difference could be found between the CBD and IPD groups for these ratios, although relatively even, decreased uptakes in the caudate nucleus and putamen were found in the CBD group. On further analysis of the index of binding reduction, the differences between the caudate nucleus and putamen were significantly lower in the CBD group than in the IPD group. The striatal uptake of [99mTc]TRODAT-1 showed a distinct asymmetry in both the CBD and IPD patients. From this study, it can be concluded that early-stage CBD patients have a worse performance and more difficulties with daily activities than IPD patients. CBD patients demonstrated essentially similar patterns of [99mTc]TRODAT-1 binding as those with IPD. However, there was relatively more homogeneous involvement of the caudate nucleus and putamen in the CBD patients. This provides information about the differences between these patients in the early stages.

Air embolism: diagnosis with single-photon emission tomography and successful hyperbaric oxygen therapy

Venous air embolism may occur when the surgical field is above the level of the heart. We present a case of venous air embolism in a patient undergoing percutaneous nephrolithotripsy in the prone position and presenting with blindness and neurological deficits 8 h later. The clinical diagnosis of paradoxical air embolism was confirmed by early single-photon emission tomography (SPET), whereas magnetic resonance imaging including diffusion-weighted imaging (DW-MRI) was diagnostic only 30 h later. Hyperbaric oxygen therapy was successful. In this case, early DW-MRI scan was inconclusive, but a SPET study of the brain appeared to be useful in confirming the clinical diagnosis. Early hyperbaric oxygen was demonstrated to be a successful therapy.

Diazepam effects on the cerebral responses to tonic pain: a SPET study.

Pain is a complex phenomenon with a strong affective-emotional component in addition to a sensory-discriminative one. This causes the activation of multiple brain areas, which process different aspects of pain simultaneously. We investigated the effects of diazepam (DZ) on a well-known pattern of brain regions activated by cold, tonic pain stimuli. Quantitative cerebral blood flow (CBF) was assessed by single photon emission tomography (SPET) and the Xe-133 inhalatory method, at rest and during tonic pain activation in eight normal, right-handed, male volunteers. The cold pressor test (CPT) was performed by immersion of the left hand in cold water twice, first during CPT alone, and again 30 min after intravenous administration of diazepam (CPT+DZ). During CPT we observed a significant CBF increase in the right thalamus, primary sensory-motor cortex (S1/M1), frontal and temporal regions, and in the left temporal region and anterior cingulate cortex (ACC). During CPT+DZ, the average CBF was significantly lower than during the CPT state (-11%, P<0.05). After normalisation, during CPT+DZ we again observed a significant CBF increase in the right thalamus, S1/M1 and frontal regions, and in the left ACC, though not in the temporal regions. DZ administration first causes a global reduction in CBF, then modifies the pattern of brain activation. During CPT, activation of the temporal regions has been interpreted as part of the affective-emotional component of pain response. DZ seems to affect the "pain-related" pattern of activation by abolishing the CBF increase in the temporal regions, without, however, modifying the pain perception or determining a sedating effect.

Cerebral perfusion and haemodynamics measured by SPET in symptom-free patients with transient ischaemic attack: clinical implications.

Transient ischaemic attacks (TIAs) are heterogeneous from the clinical, physiopathological, aetiological and prognostic points of view. Single-photon emission tomography (SPET) may influence patient management by helping to define the vascular topography and by suggesting the probable mechanism (embolic or haemodynamic). However, the variables predicting focal regional cerebral blood flow (rCBF) and cerebrovascular reserve (CVR) abnormalities on SPET and their clinical correlation are poorly known. Our objective in this study was to assess the value of rCBF and CVR measured by SPET in a prospective series of 42 patients with recent (within the preceding 30 days) first-ever TIA Two SPET examinations [baseline and post-acetazolamide (ACZ)] were consecutively performed, and region/reference ratios were obtained using an irregular region of interest (ROI) method. Percentages of interhemispheric asymmetry between homologous brain regions were used to identify abnormalities on baseline SPET, and the percentage changes in asymmetry between the baseline and post-ACZ SPET studies were used to identify abnormal responses to the vasodilator stimulus. Mean baseline and test-retest values previously obtained in normals were used as a reference. The relationship of SPET findings with clinical data and results of complementary examinations was assessed. Most patients (98%) had abnormal findings on either baseline (43%), post-ACZ (19%) or both SPET studies (36%). Thus, 33 patients had hypoperfusion on baseline SPET (78.5%, symptom related in 45%). In 23 patients, a poor response to ACZ was found (55%, symptom related in 21.5%). No predictors for rCBF or CVR impairment were found. Most patients with a first-ever TIA episode present focal hypoperfusion on SPET, either with or without correlation with TIA symptoms. Post-ACZ SPET increases the probability of finding cerebrovascular abnormalities, and orients attention towards an haemodynamic compromise. Focal hypoperfusion on SPET should not be viewed as clinically insignificant because it probably reflects previous or ongoing clinical and/or subclinical episodes of cerebral ischaemia.

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.

A non-invasive, quantitative method to demonstrate the early effects of therapy in acute pulmonary embolism.

The objective of this study was to quantify the changes in pulmonary perfusion due to therapy for pulmonary embolism (PE). To this end, seven consecutive patients (five men, two women; mean age 64+/-10 years) were studied. After basal pulmonary arteriography had demonstrated the presence of massive PE, patients were injected intravenously with 4 mCi of technetium-99m-labelled human albumin microspheres and were treated soon thereafter with a 2-h infusion of either alteplase 100 mg (five patients) or heparin 1,750 IU/h (two patients). Then, a second pulmonary arteriography study was obtained, and soon afterwards a single-photon emission tomographic (SPET) perfusion scan was performed. Immediately thereafter, a second intravenous injection of 4 mCi of 99mTc-labelled microspheres was administered, followed by a second SPET scan. At the end of the study, the perfusion changes due to therapy were quantified by subtraction of the images of the two SPET studies; the reperfused areas could be visualised and the volumes of reperfusion quantified. This study demonstrates the validity of a newly devised, relatively rapid and non-invasive method for quantification of the early effects of therapy on pulmonary perfusion in patients presenting with acute PE.

Probing targets for antipsychotic drug action with PET and SPET receptor imaging.

The use of in vivo receptor imaging by positron emission tomography (PET) and single photon emission tomography (SPET) has permitted exploration of targets for antipsychotic drug action in living patients. Early PET and SPET studies focused on striatal D2 dopamine receptors. There is broad agreement that unwanted extrapyramidal (parkinsonian) side effects of antipsychotic drugs result from high striatal dopamine D2/D3 receptor blockade by these drugs. The dopamine hypothesis of antipsychotic drug action suggests that clinical response is directly related to the level of striatal D2/D3 receptor occupancy of antipsychotic drugs. This may be true for classical antipsychotic drugs, but recent evidence suggests that novel, atypical antipsychotic drugs produce efficacy in association with modest and transient striatal D2/D3 receptor occupancy levels. Furthermore, atypical antipsychotic drugs appear to show preferential occupancy of limbic cortical dopamine D2 receptors. Cortical dopamine D2/D2-like receptors may be a common site of action for all antipsychotic drugs. Data from receptor challenge paradigms has highlighted the need to explore the neurotransmitter systems involved in regulating or stabilising dopamine transmission, either via dopamine autoreceptors or non-dopaminergic pathways. These may be promising targets for drug development. In vivo PET and SPET imaging has produced unique data contributing to the design of better, less toxic drugs for schizophrenia.

Monitoring the chemotherapeutic response in primary lung cancer using (99m)Tc-MIBI SPET.

Prediction and evaluation of the response to chemotherapy (CTx) are important for the correct and cost-effective treatment of patients with primary lung cancer. Although fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is accepted as the most useful and accurate nuclear medicine technique for this purpose, its expense and limited availability restrict its use. Compared with PET agents, technetium-99m methoxyisobutylisonitrile (MIBI), which is used in nuclear oncology, is cheaper and available in any nuclear medicine clinic. With this in mind, in this study we aimed to evaluate the role of (99m)Tc-MIBI in monitoring the chemotherapeutic response in primary lung cancer. Twenty patients with primary lung cancer underwent (99m)Tc-MIBI single-photon emission tomography (SPET) at 15min (early) and 3-4h (delayed) after injection of the tracer. All patients underwent (99m)Tc-MIBI SPET study twice: before and after the 3rd cycle of CTx. Patients were divided into two groups, responders [R(+), n=10] and non-responders [R(-), n=10], according to the change in tumour size on CT scan taken 2 weeks after the last cycle of the CTx. From the SPET images early and delayed tumour/lung ratios (ER and DR) were obtained before and after CTx. In the R(+) group, ER and DR decreased significantly after CTx, from 3.28±1.55 to 1.78±0.72 (P<0.04) and from 3.23±1.55 to 2.0±0.88 (P<0.05), respectively. However, in the R(-) group, while ER showed a slight and statistically insignificant increase after CTx (from 2.51±1.23 to 2.65±1.86), DR increased significantly, from 2.74±1.37 to 3.27±2.31 (P<0.03). The percentage decreases in ER and DR in the R(+) group after CTx was significantly higher than that in the R(-) group: 34.36%±26.7% vs -13.78%±27.58% (P<0.0002) and 29.45%±25.23% vs -18.58%±20.51% (P<0.0005), respectively. Using a decrease of ≥10% as a threshold for monitoring the chemotherapeutic response, (99m)Tc-MIBI had a sensitivity of 90% and a specificity of 100%. We found a positive correlation in 14 patients between ER and DR and survival: r=0.6754 and P=0.008, and r=0.5755 and P=0.031, respectively. Our results suggest that (99m)Tc-MIBI might be used in routine practice to monitor the chemotherapeutic response in patients with primary lung cancer, especially when PET is not available.

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

Age- and gender-specific differences in left ventricular cardiac function and volumes determined by gated SPET.

The aim of this study was to determine normative volumetric data and ejection fraction values derived from gated myocardial single-photon emission tomography (SPET) using the commercially available software algorithm QGS (quantitative gated SPET). From a prospective database of 876 consecutive patients who were referred for a 2-day stress-rest technetium-99m tetrofosmin (925 MBq) gated SPET study, 102 patients (43 men, 59 women) with a low (<10%) pre-test likelihood of coronary disease were included (mean age 57.6 years). For stress imaging, a bicycle protocol was used in 79 of the patients and a dipyridamole protocol in 23. Left ventricular ejection fraction (LVEF) and end-diastolic and -systolic volumes (EDV and ESV) were calculated by QGS. EDV and ESV were corrected for body surface area, indicated by EDVi and ESVi. To allow comparison with previous reports using other imaging modalities, men and women were divided into three age groups (<45 years, > or =45 years but <65 years and > or =65 years). Men showed significantly higher EDVi and ESVi values throughout and lower LVEF values when compared with women in the subgroup > or =65 years (P<0.05, ANOVA). Significant negative and positive correlations were found between age and EDVi and ESVi values for both women and men and between LVEF and age in women (Pearson P< or =0.01). LVEF values at bicycle stress were significantly higher than at rest (P=0.000, paired t test), which was the result of a significant decrease in ESV (P=0.003), a phenomenon which did not occur following dipyridamole stress (P=0.409). The data presented suggest that LVEF and EDVi and ESVi as assessed by QGS are strongly gender-specific. Although the physiological significance of these results is uncertain and needs further study, these findings demonstrate that the evaluation of cardiac function and volumes of patients by means of QGS should consider age- and gender-matched normative values.