Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([¹²³I]IBZM), a D₂ receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [¹²³I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [¹²³I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: –1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [¹²³I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.     

In vivo effects of olanzapine on striatal dopamine D2/D3 receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D₂/D₃ receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [¹²³I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [¹²³I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [¹²³I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D₂/D₃ receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR–BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D₂/D₃ receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR–BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D₂/D₃ receptor availability revealed an exponential dose-response relationship (r=–0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D₂/D₃ availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D₂/D₃ striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D₂/D₃ receptor affinity and a similar 5HT₂ receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D₂/D₃ receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D₂/D₃ and 5HT₂ receptor antagonism. Received 6 March 1999 / in revised form 11 April 1999     

A simplified method for quantitation of iodine-123 iodobenzamide in human plasma: a technical note

To establish a quantitative single-photon emission tomography (SPET) procedure for imaging CNS D₂ dopamine receptors, measurement of unchanged iodine-123 iodobenzamide (¹²³I-IBZM) (a selective D₂ ligand) in human plasma was investigated. There are three possible radioactive components in human plasma: hydrophilic compounds (iodide ion, etc.), lipophilic metabolites, and unchanged IBZM. Based on the difference in lipophilicity of IBZM and its lipophilic metabolites (LM), a new quantitative method of analysis of ¹²³I-IBZM using a simple solvent extraction was developed. The selective extraction was achieved with n-octane/phosphate buffer (0.1 M, pH 7.4). Extraction efficiency was 93.2% ± 0.3% (n=15) for IBZM from plasma, while 99.3% ± 0.2% (n =12) of LM remained in the aqueous plasma fraction. Twenty-one confirmation tests with plasma containing known ratios of IBZM/LM, ranging between 0.39 and 7.60, were performed. The experimental results were very close to the values of the true ratios over the wide range (accuracy 99%, relative standard error 6.6%). The data from this simplified method are comparable to those obtained by the high-performance liquid chromatography method. This improved method provides an easy and accurate way to quantify unchanged IBZM in human plasma. With appropriate kinetic modeling and in conjunction with a dedicated SPET imaging device for measuring quantitative information, it may be possible to develop a practical method for measuring D₂ receptor density in vivo. Correspondence to: Mei-Ping T. Kung     

A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography

Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K ₁, influx rate constant;k ₂, efflux rate constant;V _T (=K ₁/k ₂), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function ofk ₂, and a table lookup procedure provides the correspondingk ₂ value, from whichK ₁ andV _T values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age±SD, 56.0±12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of theV _T value of Iomazenil. Good correlations were observed betweenV _T values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations:r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use.     

In vivo imaging of GABAA receptors using sequential whole-volume iodine-123 iomazenil single-photon emission tomography

Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABA_A receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8±3.9 years). The patterns obtained were largely compatible with the known distribution of GABA_A receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest¹²³I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific¹²³I-iomazenil binding in neocortical and cerebellar regions from 60–75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume¹²³I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia.     

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     

Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography

The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D₂ receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91±0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45–60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [¹²³I]epidepride can be used for imaging striatal and extrastriatal dopamine D₂ receptor sites in the living human brain.     

Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D₂ receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D₂ receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD.The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0.002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0.001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D₂ receptor density can be detected with ¹²³I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD. Received 1 May and in revised form 29 June 1999     

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [¹²³I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [¹²³I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intea-observer variability was 3.6% and inter-observer results showed consistent differences in [¹²³I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [¹²³I]4-iododexetimide binding is reduced in patients with mild probable. Alzheimer's disease in areas of temporal and temporoparietal cortex.     

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.     

Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine single-photon emission tomography in patients with Joseph disease

Regional cerebral blood flow (rCBF) was measured in five Japanese patients who were clinically diagnosed as having Joseph disease, also called Machado-Joseph disease or Azorean disease, using N-isopropyl p-[¹²³I]iodoamphetamine (IMP) and single-photon emission tomography (SPET). Cerebellar atrophy was evaluated by a five-step rating scale as defined on X-ray computed tomography (X-CT). Compared with ten age-matched normal controls (mean cerebellar CBF ± SD: 66.9 ± 6.6 ml/100 g/min), rCBF in patients with Joseph disease was significantly decreased in the cerebellum (mean ± SD: 50.2 ± 7.3 m1/100 g/min). No significant relationship, however, was found between the decrease in rCBF in the cerebellum and the degree of cerebellar atrophy on X-CT. rCBF in the cerebellum was minimally decreased in one patient who had severe cerebellar atrophy and in two patients with moderate atrophy. These data may support the findings that Purkinje cells in the cerebellum are almost normal in Joseph disease, and that the granular and molecular layers remain intact in spite of cortical atrophy of the cerebellum. It is concluded that [¹²³I]-IMP SPET is able to identify pathological and metabolic changes in the cerebellum that do not appear on X-CT or magnetic resonance imaging, and thus is useful for the diagnosis of Joseph disease. Correspondence to: N. Takahashi     

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     

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time

Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [¹²³I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.     

Iodine-123 α-methyl-l-tyrosine single-photon emission tomography for the visualization of head and neck squamous cell carcinomas

The uptake of iodine-123 α-methyl-l-tyrosine (IMT) in the primary tumours and metastatic lymph nodes of squamous cell carcinoma of the head and neck was examined with single-photon emission tomography (SPET). Eleven patients with biopsy-proven carcinomas were studied prior to any therapeutic action. The evaluation of cervical lymph node involvement was based on the findings of physical examination, computed tomography and magnetic resonance imaging, and in six patients on the histological data relating to tissue samples obtained by fine-needle lymph node aspiration or surgical intervention. SPET imaging was performed 10 min after the injection of 130–170 MBq IMT using a triple-head gamma camera equipped with medium-energy collimators. High-quality IMT SPET depicted the primary tumour in 10 of 11 patients (sensitivity: 91%). Tumours located in the larynx were visualized more clearly than those located in the mouth or oropharynx. The mean tumour-to-background ratio was 2.35 (range: 1.6–3.1) for laryngeal tumours and 1.67 (range: 1.2–2.2) for mouth and oropharyngeal tumours. Metastatic cervical lymph nodes were involved to various degrees in 8 of the 11 patients. Among these eight patients there were 16 sites, nine of which were detected by IMT SPET (sensitivity: 56%). If the IMT SPET findings were recorded per side of the neck, the sensitivity was 64%. Five of the seven missed metastatic lymph nodes were smaller than 15 mm. The mean tumour-to-background ratio of the scintigraphically visualized lymph nodes was 1.81±0.51 (range: 1.39–2.77). Asymmetric physiological submandibular salivary gland IMT uptake led to false-positive lymph node assessment in three patients. This study indicates the potential use of IMT SPET as a metabolic imaging modality in patients with head and neck squamous cell carcinoma. Received 28 August and in revised form 25 October 1997     

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [¹²³I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [¹²³I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [¹²³I]MIBG planar and single-photon emission tomography (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the¹²³I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31±0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4±2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [¹²³I]MIBG uptake.     

A method to quantitate cerebral blood flow using a rotating gamma camera and iodine-123 iodoamphetamine with one blood sampling

A method has been developed to quantitate regional cerebral blood blow (rCBF) using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique requires only two single-photon emission tomography (SPET) scans and one blood sample. Based on a two-compartment model, radioactivity concentrations in the brain for each scan time (early: t _e ; delayed: td) aredescribed as: % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGLbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadwga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGLbaabeaaaaa!4D64!\[C_t \left( {t_e } \right) = fC_a \left( {t_e } \right) \otimes e\frac{f}{{V_d }}t_e \] and % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGKbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadsga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGKbaabeaaaaa!4D61!\[C_t \left( {t_d } \right) = fC_a \left( {t_d } \right) \otimes e\frac{f}{{V_d }}t_d \] respectively, where denotes the convolution integral; C _a (t), the arterial input function; f rCBF; and V _d , the regional distribution volume of IMP. Calculation of the ratio of the above two equations and a table look-up procedure yield a unique pair of rCBF and V _d for each region of interest (ROI). A standard input function has been generated by combining the input functions from 12 independent studies prior to this work to avoid frequent arterial blood sampling, and one blood sample is taken at 10 min following IMP administration for calibration of the standard arterial input function. This calibration time was determined such that the integration of the first 40 min of the calibrated, combined input function agreed best with those from 12 individual input functions (the difference was 5.3% on average). This method was applied to eight subjects (two normals and six patients with cerebral infarction), and yielded rCBF values which agreed well with those obtained by a positron emission tomography H₂ ¹⁵O autoradiography method. This method was also found to provide rCBF values that were consistent with those obtained by the non-linear least squares fitting technique and those obtained by conventional microsphere model analysis. The optimum SPET scan times were found to be 40 and 180 min for the early and delayed scans, respectively. These scan times allow the use of a conventional rotating gamma camera for clinical purposes. V _d values ranged between 10 and 40 ml/g depending on the pathological condition, thereby suggesting the importance of measuring V _d for each ROI. In conclusion, optimization of the blood sampling time and the scanning time enabled quantitative measurement of rCBF with two SPET scans and one blood sample.     

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     

Cardiac <Superscript>123</Superscript>I-metaiodobenzylguanidine imaging allows early identification of dementia with Lewy bodies during life

PURPOSE: Differential diagnosis between dementia with Lewy bodies (DLB) and other neurodegenerative diseases with cognitive impairment represents a clinical challenge. Due to the overlapping of symptoms, the clinical diagnosis can be modified during the prolonged follow-up of these diseases. The purpose of this study was to assess the ability of cardiac metaiodobenzylguanidine (MIBG) imaging for early identification of DLB. MATERIALS AND METHODS: Since January 2003, all patients with neurodegenerative diseases with cognitive impairment at their first visit at the Memory Unit and clinical criteria of DLB were consecutively recruited and underwent a cardiac (123)I-MIBG study. The heart-to-mediastinum ratio (HMR) and the washout rate (WR) of cardiac MIBG uptake were obtained. RESULTS: Sixty-five patients were included. After a clinical follow-up of 4 years, the progress of the disease procured a definite diagnosis in 44 (68%) patients: 19 DLB, 12 Alzheimer disease (AD), and 13 other neurodegenerative diseases with cognitive impairment. HMR was significantly decreased in DLB with respect to the other neurodegenerative diseases. WR was only significantly different between DLB and AD. The HMR cut off point of 1.36 differentiated DLB from the other dementias with a sensitivity of 94% and a specificity of 96% with an accuracy of 95%. CONCLUSIONS: Cardiac MIBG imaging performed at the time of the first clinical diagnosis of DLB can help early clinical identification or exclusion of this disease.     

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus²⁰¹TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of²⁰¹TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (²=8.5) followed by the number of coronary stenoses on angiography (²=3.9). These preliminary data suggest that decreased BMIPP uptake relative to²⁰¹TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.Presented in part at the 40th Annual Meeting of Society of Nuclear Medicine at Orlando, Florida, June 1994     

Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia

This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D₂ receptor concentrations measured by iodine-123 iodobenzamide (¹²³I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D₂ receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand¹²³I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D₂ receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is −1.52 (95% CI −3.72−0.66) and for patients 4.04 (95% CI 1.07−7.01). Analysis of variance shows a caseby-sex-by-side interaction, withF=10.01,P=0.005. We can now demonstrate that the previously observed male sex-specific D₂ receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D₂ asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatallimbic circuits in schizophrenic males.