Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: Comparison with brain perfusion SPET and FDG PET

Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of¹²³I-IMZ (167 MBq). Parametric images of the ligand transport (K ₁) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.     

Benzodiazepine receptors and cerebral blood flow in partial epilepsy

It was the aim of this study to compare benzodiazepine (Bz) receptor binding and cerebral perfusion in patients with partial epilepsy. Single photon emission tomography (SPET) studies with the flow-marker technetium 99m hexamethylpropylene amine oxine (^99mTc-HMPAO) and with the¹²³I-labelled Bz-receptor ligand Ro 16-0154 (¹²³I-Iomazenil) were performed in 12 patients with partial epilepsy, all with normal magnetic resonance imaging (MRI) and computed tomography (CT) scans. The SPET studies with¹²³I-Iomazenil were carried out 5 min and 2 h after injection. At 2 h the distribution of activity was very similar to the expected distribution of Bz-receptors in the human brain, known from positron emission tomography (PET) work and post-mortem studies. Early images showed a significantly higher tracer accumulation in the area of the basal ganglia, cerebellum, and naso-pharyngeal space. This finding is caused by non-specific binding and the contribution of the tracer in the blood pool in this phase. Also after 2 h p.i. of¹²³I-Iomazenil, 9 of the 12 patients showed a focal decrease of of Bz-receptor binding. Ten patients had focal flow abnormalities with^99mTc-HMPAO SPET. In 8 subjects impairment of flow was seen in sites of reduced¹²³I-Iomazenil uptake.¹²³I-Io-mazenil is suitable for Bz-receptor mapping. In this series of patients, Bz-receptor mapping with SPET seems to offer no advantage over^99mTc-HMPAO in the detection of epileptic foci. Offprint requests to: P. Bartenstein     

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography

IPT [N-(3-iodopropen-2-yl)-2-carbome-thoxy-3-(4-chlorophenyl) tropane] is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1–2 h post injection. In the present study [¹²³I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40–79 years) and eight age-matched controls were studied. SPET imaging was performed 90–120 min after injection of 160–185 MBq [¹²³I]IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I]IPT binding was significantly correlated with disease duration (r=–0.7,P<0.0001) but not with the age of PD patients (r=–0.10,P=0.61). Specific [¹²³I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [¹²³I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [¹²³I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.     

Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: comparison with brain perfusion SPET and FDG PET

. Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15rmin (early) and 3rh (late) after intravenous injection of ¹²³I-IMZ (167rMBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers’ input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.     

[I/F] N-(2-aminoethyl)-5-halogeno-2-pyridinecarbox-amides, site specific tracers for MAO-B mapping with SPET and PET

After the successful ¹²³I-labelling of Ro 43-0463 the new radiopharmaceutical was tested in animals and humans. Both investigations proved the binding of the labelled compound to cerebral MAO-B. SPET investigations resulted in an imaging of the MAO-B distribution in the human brain. This prompted us to develop the labelling of this type of MAO-B inhibitor with ¹⁸F enabling us to transfer our results to PET.     

Non-invasive grading of primary brain tumours: Results of a comparative study between SPET with123I-α-methyl tyrosine and PET with18F-deoxyglucose

Use of iodine-123--methyl tyrosine (¹²³I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of¹²³I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (¹⁸F-FDG);¹²³I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3.¹⁸F-FDG and¹²³I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71,P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for¹⁸F-FDG uptake and 1.8 for¹²³I-IMT uptake, the accuracy values of¹⁸F-FDG PET and¹²³I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of¹²³I-IMT SPET on the therapeutic management of patients with brain tumours.     

Upregulation of putaminal dopamine D2 receptors in early Parkinson's disease: a comparative PET study with [11C] raclopride and [11C]N-methylspiperone.

Dopamine D2 receptor function was assessed in a PET study with 2 dopamine D2 receptor PET ligands, [11C]raclopride (RAC) and [11C]N-methylspiperone (NMSP), in early Parkinson's disease. METHODS: Seven patients with early Parkinson's disease and 5 healthy volunteers were studied. Each underwent PET both with reversible [11C]RAC and with irreversible [11C]NMSP. RESULTS: Upregulation of dopamine D2 receptors in the putamen contralateral to the predominant symptoms of Parkinson's disease was confirmed using both [11C]RAC and [11C]NMSP. Uptake of [11C]RAC in the contralateral putamen was 105% of uptake in the opposite putamen (P = 0.020). For [11C]NMSP, uptake in the contralateral putamen was 105% of uptake in the ipsilateral putamen (P = 0.011). No significant differences between Parkinson's disease patients and healthy volunteers were detected in any of the studied brain regions using either [11C]RAC or [11C]NMSP. No significant differences between [11C]RAC and [11C]NMSP uptake were detected in the striatum, whereas in the extrastriatal regions, [11C]NMSP showed significantly higher uptake than [11C]RAC both in healthy volunteers and in Parkinson's disease patients. CONCLUSION: This study confirms an increase in dopamine D2 receptors in the putamen contralateral to the predominant symptoms, compared with the ipsilateral putamen, in early Parkinson's disease. This increase was seen both with reversible ligand [11C]RAC and with irreversible ligand [11C]NMSP and thus does not seem a consequence of depleted endogenous dopamine.     

Temporal lobe epilepsy: Correlation of proton magnetic resonance spectroscopy and 18F-fluorodeoxyglucose positron emission tomography

Proton magnetic resonance spectroscopy (MRS) has demonstrated reduction of N-acetylaspartate (NAA) in the epileptogenic temporal lobe. However, the correlation of NAA reduction with cerebral metabolic abnormalities is unknown in temporal lobe epilepsy (TLE). Proton MRS and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG/PET) were used to study 12 unilateral TLE patients with medically intractable seizures and 26 age-matched healthy volunteers. The epileptogenic temporal lobe of each patient was determined by both electroencephalography and FDG/PET. The NAA/choline-plus-creatine (NAA/(Cho+Cr)) ratio correlated significantly with the interictal glucose metabolism (r = 0.54, P 0.01) in 12 TLE patients. The mean NAA/(Cho + Cr) ratio in the epileptogenic temporal lobe was significantly less than that in the contralateral side (P < 0.01), and less than that in normal control temporal lobes (P < 0.0001). These results suggest that quantitative MRS abnormalities reflect underlying metabolic pathology in TLE.     

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.     

Benzodiazepine receptors and cerebral blood flow in partial epilepsy.

It was the aim of this study to compare benzodiazepine (Bz) receptor binding and cerebral perfusion in patients with partial epilepsy. Single photon emission tomography (SPET) studies with the flow-marker technetium 99m hexamethylpropylene amine oxine (99mTc-HMPAO) and with the 123I-labelled Bz-receptor ligand Ro 16-0154 (123I-Iomazenil) were performed in 12 patients with partial epilepsy, all with normal magnetic resonance imaging (MRI) and computed tomography (CT) scans. The SPET studies with 123I-Iomazenil were carried out 5 min and 2 h after injection. At 2 h the distribution of activity was very similar to the expected distribution of Bz-receptors in the human brain, known from positron emission tomography (PET) work and post-mortem studies. Early images showed a significantly higher tracer accumulation in the area of the basal ganglia, cerebellum, and naso-pharyngeal space. This finding is caused by non-specific binding and the contribution of the tracer in the blood pool in this phase. Also after 2 h p.i. of 123I-Iomazenil, 9 of the 12 patients showed a focal decrease of of Bz-receptor binding. Ten patients had focal flow abnormalities with 99mTc-HMPAO SPET. In 8 subjects impairment of flow was seen in sites of reduced 123I-Iomazenil uptake. 123I-Iomazenil is suitable for Bz-receptor mapping. In this series of patients, Bz-receptor mapping with SPET seems to offer no advantage over 99mTc-HMPAO in the detection of epileptic foci.     

Sequential 123I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18F-FDG PET imaging)

Purpose Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with ¹²³I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci.Methods We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation.Results The 6-h IDEX scan (92%; =0.83, p=0.003) was superior to the 0-h (36%; =0.01, p>0.05), 3-h (55%; =0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; =0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy.Conclusion The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.     

Differential distribution of striatal [123I]β-CIT in Parkinson’s disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([¹²³I]β-CIT) is important for the assessment of disease severity and progression in patients with Parkinson’s disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [¹²³I]β-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24±2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3′′). ANOVA revealed a global reduction of V3′′ in all ROIs of PD and PSP patients compared with normal controls (P<0.0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3′′ caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [¹²³I]β-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP. Received 1 February and in revised form 7 May 1998     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy

Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [¹²³I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.     

Initial human studies with single-photon emission tomography using iodine-123 labelled 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]-benzodiazepine (NNC 13-8241)

The iodine-123 labelled ligand 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5-methyl-6oxo-4H-imidazo[1,5-a][1,4]-benzodiazepine ([¹²³I]NNC 13-8241) was evaluated as a probe for in vivo imaging of benzodiazepine receptor sites in the human brain. Four healthy volunteers were imaged with a high-resolution single-photon emission tomography (SPET) scanner. The metabolism of [¹²³I]NNC 13-8241 in plasma was slow. The total brain uptake was about 1.5-fold higher than that of [¹²³I]iomazenil. The specific binding in the cortical areas was high and less intense in the thalamus. The most intense uptake was seen in the occipital cortex. The peak cortical uptake of [¹²³I]NNC 13-8241 was observed 6–10 h after the injection of tracer. The radiation burden to the patient was moderate, being 2.5·10^–2 mSv/MBq (effective dose equivalent). A slow metabolism together with favourable kinetics indicates that [¹²³I]NNC 13-8241 is a specific and promising SPET ligand for imaging benzodiazepine receptor sites in the living human brain.     

Iterative reconstruction with correction of the spatially variant fan-beam collimator response in neurotransmission SPET imaging

The dopamine transporter (DAT) has been shown to be a sensitive indicator of nigrostriatal dopamine function. Although visual inspection is often sufficient to assess DAT imaging, quantification could improve the diagnostic accuracy of single-photon emission tomography (SPET) studies of the dopaminergic system. The aim of this study was to assess the accuracy of quantification of the striatal/background uptake ratio when correction for attenuation, scatter and spatially variant fan-beam collimator response is performed in technetium-99m and iodine-123 SPET imaging. A numerical striatal phantom was implemented, and simulated projections of low-energy photons were obtained by using the SimSET Monte Carlo code. High-energy contamination in ¹²³I studies was modelled from experimental measurements with ^99mTc and ¹²³I. The ordered subsets expectation maximisation (OSEM) algorithm was employed in reconstruction. Mean improvements of 8% and 16% were obtained in the calculated striatal/background uptake ratio in the putamen and the caudate, respectively, when the spatially variant point spread function was included in the transition matrix. Ideal scatter correction resulted in improvements in the putamen and caudate of 9% for ^99mTc agents and 19% for ¹²³I agents. Improvements averaged 31% in the putamen and 43% in the caudate when correction for attenuation, scatter and spatially variant collimator response was included in the reconstruction.     

Sympathetic innervation of the left ventricle is impaired in arrhythmogenic right ventricular disease

Arrhythmogenic right ventricular disease (ARVD) is a disease of unknown origin that primarily affects the right ventricle and is characterized by ventricular tachyarrhythmias which may lead to syncope and even, though rarely, sudden cardiac death. In 25 patients with ARVD, sympathetic innervation of the left ventricle was assessed by iodine-123 metaiodobenzylguanidine single photon emission tomography (1231-MIBG SPET). In addition, thallium-201 SPET was performed. The diagnosis of ARVD was made by an electrophysiological study and right and left heart catheterization including right ventricular endomyocardial biopsy. Ischaemic heart disease was excluded by coronary angiography. A group of seven patients without any evidence of heart disease served as a control group. Twenty-two of the 25 patients showed reduced uptake of ¹²³I-MIBG. The abnormal areas were located predominantly in posterior and posteroseptal segments of the heart. No focus of increased ¹²³I-MIBG activity could be demonstrated. No patient had signs of left ventricular involvement on left ventricular angiography. In contrast to the results of the ¹²³I-MIBG SPET, those of ²⁰¹TI SPET were normal in 16 patients. The remaining nine patients showed areas of slight hypoperfusion not correlated with the reduced ¹²³I-MIBG uptake. ¹²³I-MIBG scintigraphy allows detection of left ventricular adrenergic dysinnervation in ARVD patients without morphological or functional abnormalities of the left ventricle. Correspondence to: H. Lerch     

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with123I-BMIPP and201TI

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method JEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included.²⁰¹T1 cross-talk into the¹²³I acquisition window (group 1,n = 30) and¹²³I cross-talk into the²⁰¹Tl window (group 2,n = 41) were studied. In group 1,¹²³I images were first obtained (single-isotope images), followed by²⁰¹Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual¹²³I-BMIPP/²⁰¹Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.     

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and ¹²³I-IBZM SPET for the in vivo imaging of dopamine D₂ receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of ¹²³I-epidepride, but only one showed specific binding of ¹²³I-IBZM. Specific binding of ¹²³I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of ¹²³I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of ¹²³I-epidepride in the pituitary region was consistently higher than that of ¹²³I-IBZM. None of the patients who showed absence of uptake of ¹²³I-epidepride in the pituitary area showed uptake of ¹²³I-IBZM in this area. In conclusion: ¹²³I-epidepride SPET is superior to ¹²³I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, ¹²³I-epidepride should replace ¹²³I-IBZM for future D₂ receptor SPET studies of pituitary adenomas. ¹²³I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy. Received 11 July and in revised form 25 September 1998     

123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects

5-HT_2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT_2A receptors, ¹²³iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of ¹²³I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23–60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT_2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42%±7% was found. These results are in agreement with in vitro and positron emission tomography findings of a decline in 5-HT_2A receptor binding with age. The findings confirm the suitability of ¹²³I-5-I-R91150 for SPET imaging of 5-HT_2A receptors, and highlight the necessity for age-matched controls in clinical studies. Received 21 March and in revised form 18 August 1998