Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D₂ receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism

[123I]FP-CIT (N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several "presynaptic parkinsonian" syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [123I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with "presynaptic parkinsonism" from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [123I]FP-CIT SPET. Using [123I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [123I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases, and in three cases no conclusive diagnosis was established, but presynaptic parkinsonism was excluded clinically. A clinical diagnosis of presynaptic parkinsonism was established in two cases: one case of multiple system atrophy (in this patient loss of dopamine D2 receptors was found with [123I]iodobenzamide SPET performed 2 weeks after [123I]FP-CIT imaging) and one case of Parkinson's disease. Our data suggest that the positive predictive value of [123I]FP-CIT imaging is very high, and although the negative predictive value is lower, dopamine transporter imaging offers the prospect of a quick, objective method to confirm or exclude presynaptic parkinsonism in inconclusive cases.     

Imaging of dopamine transporters in rats using high-resolution pinhole single-photon emission tomography

To date, the vast majority of investigations on the dopaminergic system in small animals have been in vitro studies. In comparison with in vitro studies, single-photon emission tomography (SPET) or positron emission tomography (PET) imaging of the dopaminergic system in small animals has the advantage of permitting repeated studies within the same group of animals. Dopamine transporter imaging is a valuable non-invasive tool with which to investigate the integrity of dopaminergic neurons. The purpose of this study was to investigate the feasibility of assessing dopamine transporter density semi-quantitatively in rats using a recently developed high-resolution pinhole SPET system. This system was built exclusively for imaging of small animals. In this unique single-pinhole system, the animal rotates instead of the collimated detector. The system has proven to have a high spatial resolution. We performed SPET imaging with [(123)I]FP-CIT to quantify striatal dopamine transporters in rat brain. In all seven studied control rats, symmetrical striatal binding to dopamine transporters was seen 2 h after injection of the radiotracer, with striatal-to-cerebellar binding ratios of approximately 3.5. In addition, test/retest variability of the striatal-to-cerebellar binding ratios was studied and found to be 14.5%. Finally, in unilaterally 6-hydroxydopamine-lesioned rats, striatal binding was only visible on the non-lesioned side. Quantitative analysis revealed that striatal-to-cerebellar SPET ratios were significantly lower on the lesioned (mean binding ratio 2.2 +/- 0.2) than on the non-lesioned (mean ratio 3.1 +/- 0.4) side. The preliminary results of this study indicate that semi-quantitative assessment of striatal dopamine transporter density using our recently developed high-resolution single-pinhole SPET system is feasible in living rat brain.     

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.     

Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand

The diagnosis of Parkinson's disease is based on clinical features with pathological verification. However, autopsy has been found to confirm a specialist diagnosis in only about 75% of cases. Especially early in the course of the disease, the clinical diagnosis can be difficult. Imaging of presynaptic dopamine transporters (DAT receptors) has provided a possible diagnostic probe in the evaluation of Parkinson's disease. The cocaine analogue [(123)I]-2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane ([(123)I]-beta-CIT) is one of several radioligands that have been developed for single-photon emission tomography (SPET). The purpose of this study was to evaluate the impact of [(123)I]-beta-CIT SPET on the diagnosis and clinical management of patients with a primary, tentative diagnosis of parkinsonism. We undertook a retrospective evaluation of the clinical records of 90 consecutive patients referred to [(123)I]-beta-CIT SPET from the neurological department, Bispebjerg Hospital. In 58 subjects the scans revealed altered tracer uptake consistent with Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. A significant change in the management or treatment because of the scan was found in 25 patients (28%). The sensitivity of the examination was 97% and the specificity 83%. In conclusion, a significant clinical impact of DAT receptor SPET imaging was found. DAT receptor imaging is a useful diagnostic probe in patients with a possible diagnosis of parkinsonism.     

Performance comparison of a state-of-the-art neuro-SPET scanner and a dedicated neuro-PET scanner

The physical performances of two current state-of-the-art scanners dedicated to functional imaging of the brain, one a single-photon emission tomography (SPET) scanner and the other a positron emission tomography (PET) scanner, have been compared under identical conditions. The aim of the study was to compare the capabilities of the devices under conditions resembling the routine clinical environment, as well as to consider other issues such as radiation burden for some common investigations. Both systems have slightly less than 11-cm axial fields of view. The PET system can be operated in a septa-less (3D) mode as well as conventionally with septa (2D). The spatial resolution of both devices was less than 8 mm in all dimensions in scattering media. On average, the PET scanner's resolution was approximately 10%–15% better than the SPET system. Energy resolution on the SPET system was superior due the scintillator used [Nal(Tl)]. Sensitivity in air with a line source on the PET system was found to be 150 times greater in 3D and 25 times greater in 2D than with the SPET system. A normal subject was studied on each system in an attempt to obtain the highest quality data possible for a subjective comparison. It is clear that, while PET retains the advantages of more desirable radiopharmaceuticals and higher sensitivity, the quality obtainable from SPET devices has improved markedly. SPET may prove as useful for many clinical investigations.     

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.     

Is there still a place for SPET in the era of PET brain imaging?

Although positron emission tomography (PET) may be credited with providing the impetus for the new clinical interest in functional neuroimaging and currently is an increasingly important imaging tool for noninvasive assessment of brain tumors, single-photon emission tomography (SPET) has offered an alternative technique with the relative advantages of lower price and wide availability. Brain SPET has been proven useful in the differentiation of tumor recurrence from radiation necrosis, in the non-invasive assessment of gliomas and meningiomas aggressiveness, in differentiating neoplastic from non neoplastic intracerebral haemorrhage, in monitoring treatment response and estimating patients' prognosis. Thus, SPET may still have a role in the diagnosis and characterization of brain tumors. Future comparative studies between SPET and PET or latest magnetic resonance based neuroimaging techniques are warranted.     

Transmission scanning in emission tomography

Attenuation correction in single-photon (SPET) and positron emission (PET) tomography is now accepted as a vital component for the production of artefact-free, quantitative data. The most accurate attenuation correction methods are based on measured transmission scans acquired before, during, or after the emission scan. Alternative methods use segmented images, assumed attenuation coefficients or consistency criteria to compensate for photon attenuation in reconstructed images. This review examines the methods of acquiring transmission scans in both SPET and PET and the manner in which these data are used. While attenuation correction gives an exact correction in PET, as opposed to an approximate one in SPET, the magnitude of the correction factors required in PET is far greater than in SPET. Transmission scans also have a number of other potential applications in emission tomography apart from attenuation correction, such as scatter correction, inter-study spatial co-registration and alignment, and motion detection and correction. The ability to acquire high-quality transmission data in a practical clinical protocol is now an essential part of the practice of nuclear medicine. Received: 19 February 1998 / Accepted: 19 March 1998     

Imaging of the dopaminergic system in differential diagnosis of dementia

Neurodegenerative dementia is an increasingly common disorder with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) accounting for most cases. Due to the overlap in clinical symptoms, their differential diagnosis may be challenging. As clinical classification is not completely satisfying, there is a need to improve the diagnostic accuracy by complementary methods such as functional single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. The latter may be helpful to address one distinct biological difference between DLB and AD, the severe nigrostriatal degeneration which occurs in DLB, but not to any significant extent in AD. Based on this principle, autoradiographic studies targeting presynaptic dopaminergic functions have consistently demonstrated the ability to distinguish DLB from AD in postmortem series. At the same time, several single-site and one multicentre study have independently confirmed--no matter what technique was used (SPECT or PET) and which presynaptic function was addressed (dopamine turnover, dopamine transporter, vesicular monoamine transporter)--significantly compromised scan results in DLB subjects, whereas AD patients maintained almost normal findings. Even more important, in vivo findings of presynaptic dopaminergic imaging correlated well with neuropathological findings at autopsy, suggesting a remarkable sensitivity of 88% and a specificity of 100% for the imaging procedure to distinguish between DLB and AD. Taken together, imaging of presynaptic dopaminergic terminal functions with SPECT and PET has currently the greatest evidence base to support its use, and therefore, may be highly recommended to help in the discrimination between DLB and AD. Compared to presynaptic functions, corresponding data targeting postsynaptic dopamine receptors are comparatively rare, less conclusive and suggest a very limited role for this purpose. This review discusses the findings of studies specifically dealing with imaging of the dopaminergic system in the differential diagnosis of dementia.     

The role of SPET and PET in monitoring tumour response to therapy

Positron emission tomography (PET) and single-photon emission tomography (SPET) are cross-sectional, quantitative functional imaging modalities in routine use in oncology for the initial staging of cancer, the assessment of patients with recurrent or residual disease and, more recently, for monitoring tumour response to therapy. Both PET and SPET can track tumour biological and metabolic changes caused by therapy or by disease progression, which usually precede the anatomical alterations conventionally detected by anatomical imaging methods. These highly sensitive functional imaging modalities have been used for the early assessment of subclinical tumour response, the evaluation of therapy after its completion and the detection of viable recurrent or relapsing tumour. Timely assessment of response to treatment using PET and SPET may result in modifications in treatment planning and individualisation of therapy and may have prognostic value for the long-term outcome. This review attempts to summarise the current data available on the expanding role of SPET and PET, using a variety of tracers, in monitoring tumour response to therapy in a wide range of malignancies, with emphasis on their clinical impact.     

PET measurements of dopaminergic pathways in the brain.

Positron emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow or metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways. Measurements of radioligand binding in vivo with PET reveals abnormalities associated with specific diseases and the actions of various drugs that affect the dopaminergic system. Finally, PET measurements of the uptake of analogues of levodopa provide clues to the function of dopamine pathways potentially important for diagnosis and treatment of disease like PD.     

Where have we got to with neuroreceptor mapping of the human brain?

In the past two decades, tritiated radioligand receptor binding, a tool commonly used to investigate the site of action of drugs in laboratory animals, has provided a vast body of information on neuropharmacology and neurobiology. Several neurological and psychiatric diseases have been related to neurotransmitter and receptor disorders. In order to study ligand interactions with receptors in vivo in humans, new tracers capable of carrying a gamma-emitting radionuclide to the receptor have been designed. Emission computerized tomography (ECT) techniques such as positron (PET) or single photon emission tomography (SPET) allow monitoring of the time-course of regional tissue concentration of these radiolabelled ligands. PET and SPET each have their inherent advantages and drawbacks. The cyclotron-based technology of PET is a demanding and expensive technique that, to date, is still mainly reserved for research purposes. It is hoped that once the scientific basis of a physiopathological study is established using PET, diagnostic information might be provided by the more readily available SPET technology. The purpose of this article is to review the current state of receptor-binding gamma-emitting radioligands and to present the clinical potential of these new kinds of radiopharmaceuticals in clinical investigation.     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.     

Quantification of dopamine transporters in the mouse brain using ultra-high resolution single-photon emission tomography

Functional imaging of small animals, such as mice and rats, using ultra-high resolution positron emission tomography (PET) and single-photon emission tomography (SPET), is becoming a valuable tool for studying animal models of human disease. While several studies have shown the utility of PET imaging in small animals, few have used SPET in real research applications. In this study we aimed to demonstrate the feasibility of using ultra-high resolution SPET in quantitative studies of dopamine transporters (DAT) in the mouse brain. Four healthy ICR male mice were injected with (mean+/-SD) 704+/-154 MBq [(99m)Tc]TRODAT-1, and scanned using an ultra-high resolution SPET system equipped with pinhole collimators (spatial resolution 0.83 mm at 3 cm radius of rotation). Each mouse had two studies, to provide an indication of test-retest reliability. Reference tissue kinetic modeling analysis of the time-activity data in the striatum and cerebellum was used to quantitate the availability of DAT. A simple equilibrium ratio of striatum to cerebellum provided another measure of DAT binding. The SPET imaging results were compared against ex vivo biodistribution data from the striatum and cerebellum. The mean distribution volume ratio (DVR) from the reference tissue kinetic model was 2.17+/-0.34, with a test-retest reliability of 2.63%+/-1.67%. The ratio technique gave similar results (DVR=2.03+/-0.38, test-retest reliability=6.64%+/-3.86%), and the ex vivo analysis gave DVR=2.32+/-0.20. Correlations between the kinetic model and the ratio technique ( R(2)=0.86, P<0.001) and the ex vivo data ( R(2)=0.92, P=0.04) were both excellent. This study demonstrated clearly that ultra-high resolution SPET of small animals is capable of accurate, repeatable, and quantitative measures of DAT binding, and should open up the possibility of further studies of cerebral binding sites in mice using pinhole SPET.     

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. Received 3 August and in revised form 1 October 1997     

Occupancy of dopamine D2 receptors in the mouse brain measured using ultra-high-resolution single-photon emission tomography and [123]IBF

Functional imaging of small animals, such as mice and rats, using ultra-high-resolution positron emission tomography (PET) and single-photon emission tomography (SPET) should be a valuable tool in studies of drug occupancy of cerebral binding sites. In this study we aimed to demonstrate the feasibility of using ultra-high-resolution SPET to measure the occupancy of dopamine D2 receptors by a competing drug, using the dopamine D2 receptor-specific radioligand iodine-123 5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl) methyl] carboxamido-2,3-dihydrobenzofuran ([123I]IBF). Fourteen normal male mice (CD-1) were jugular vein-cannulated and a bolus infusion protocol was used to deliver 360 MBq [123I]IBF into the mouse (bolus-to-infusion ratio 1.8:1). The mice were scanned using an ultra-high-resolution triple-headed SPET system equipped with pinhole collimators. After sustained equilibrium had been achieved, varying doses of raclopride, a potent dopamine D2 receptor antagonist, were injected through the tail vein and the tracer was allowed to regain equilibrium. A simple equilibrium ratio of striatum to cerebellum provided a measure of D2 receptor binding both before and after injection of raclopride. Following raclopride administration, the system returned to equilibrium with lower specific binding in the striatum, while the counts in the cerebellum were unaffected. Receptor occupancy was 5.2% +/- 2.9% (control), 52.1% +/- 11.1% (0.3 mg/kg), 79.3% +/- 4.8% (1.0 mg/kg), and 94.7% +/- 2.2% (3.0 mg/kg), which gave an ED50=0.26 +/- 0.03 mg/kg using a single receptor site saturation model. This study has demonstrated clearly that ultra-high-resolution SPET of small animals is capable of measuring displacement and occupancy of dopamine D2 receptors by competing ligands.     

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D₂ receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using ¹²³I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90°), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21–0.46 GBq of ¹²³I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to ¹²³I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a ¹²³I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC+AT) and (SC+CBC+AT) corrected images were compared. PET acquisitions using 0.11–0.44 GBq of ¹¹C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (%ID/100 ml) obtained after (SC+CBC+AT) in SPET are in good agreement with those obtained with PET and ¹¹C-epidepride. A method for the in vivo absolute quantitation of ¹²³I-epidepride uptake using SPET has been developed which can be directly applied to other ¹²³I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.     

18FDG PET and acetazolamide-enhanced99mTc-HMPAO SPET in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. Measurements of cerebral blood flow and metabolism by means of positron emission tomography (PET) and single-photon emission tomography (SPET) can contribute to the diagnostic assessment of the involvement of the central nervous system (CNS) in SLE. Functional imaging has been proven to be more sensitive than morphological imaging (magnetic resonance imaging and computed tomography). In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) and a PET scan with fluorine-18 deoxyglucose (¹⁸FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that preclinical CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE.     

99mTc-TRODAT-1 SPECT in healthy and 6-OHDA lesioned parkinsonian monkeys: comparison with 18F-FDOPA PET

Parkinson's disease (PD) is a degeneration of the nigrostriatal dopaminergic pathway, leading to a selective loss of dopamine in the striatum. 99mTc-TRODAT-1 is a recently developed radiotracer that selectively binds to the dopamine transporters, which are significant because loss of these transporters corresponds with a loss of dopaminergic neurons. The present investigation compared 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) with 18F-FDOPA positron emission tomography (PET) in the evaluation of PD using a primate model. Three monkeys, including one 6-hydroxydopamine lesioned PD model and two controls, were examined by both 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. For the PD monkey, expression of parkinsonian behaviour and 18F-FDOPA PET were used to evaluate the severity of the lesion. 99Tc-TRODAT-1 was prepared from a lyophilized kit. After intravenous injection of the radiotracer, SPECT was acquired over 4 h using a dual-head camera equipped with ultra-high resolution fan-beam collimators. Both uptake measurement and visual assessment were performed. Data were compared with motor behaviour and PET imaging. The striatal uptake in both healthy and PD monkeys increased continuously during the study, although the gradient of increase was less prominent in the diseased monkey. The increased uptake in the controls appeared to become blunt around 4 h after injection. A profound decrease of 99Tc-TRODAT-1 uptake was found in the striatum of the PD monkey compared with the controls (0.91 vs 2.16). In the PD monkey, the decrease of striatal uptake contralateral to the more affected side of the body was more prominent compared to the ipsilateral side (0.77 vs 1.06). In addition, greater loss occurred in the contralateral side of the putamen (0.54 vs 1.04). Changes of uptake ratios in the striatum and its subnuclei of the PD monkey were significantly correlated with those measured from PET. The loss of striatal uptake appeared greater in SPECT than the corresponding PET with both visual and uptake analyses. In conclusion, our data in a limited series of cases indicate that 99Tc-TRODAT-1 with a conventional nuclear medicine camera system may provide a suitable tool in evaluating parkinsonism in a primate model.