AMPT-induced monoamine depletion in humans: evaluation of two alternative [<Superscript>123</Superscript>I]IBZM SPECT procedures

PURPOSE: Acute monoamine depletion paradigms using alpha-methyl-para-tyrosine (AMPT) combined with single photon emission computed tomography (SPECT) have been used successfully to evaluate disturbances in central dopaminergic neurotransmission. However, severe side effects due to relatively high doses (4,500 to 8,000 mg) of AMPT have been reasons for study withdrawal. Thus, we assessed the effectiveness and tolerability of two alternative procedures, using lower doses of AMPT. METHODS: Six healthy subjects underwent three measurements of striatal dopamine D(2) receptor (D(2)R)-binding potential (BP(ND)) with SPECT and the selective radiolabeled D(2)R antagonist [(123)I]IBZM. All subjects were scanned in the absence of pharmacological intervention (baseline) and after two different depletion procedures. In the first depletion session, over 6 h, subjects were administered 1,500 mg of AMPT before scanning. In the second depletion session, over 25 h, subjects were administered 40 mg AMPT/kg body weight. We also administered the Subjective Well-being Under Neuroleptic Treatment Scale, a self-report instrument designed to measure the subjective experience of patients on neuroleptic medication. RESULTS: We found no change of mean D(2)R BP(ND) after the first and short AMPT challenge compared to the baseline. However, we found a significant increase in striatal D(2)R BP(ND) binding after the AMPT challenge adjusted for bodyweight compared to both other regimen. Although subjective well-being worsened after the prolonged AMPT challenge, no severe side effects were reported. CONCLUSIONS: Our results imply a low-dosage, suitable alternative to the common AMPT procedure. The probability of side effects and study withdrawal can be reduced by this procedure.     

Usefulness of <Superscript>201</Superscript>TlCl/<Superscript>123</Superscript>I-BMIPP dual-myocardial SPECT for patients with non-ST segment elevation myocardial infarction

OBJECTIVE: Earlier studies suggested that elevated cardiac troponin T (cTnT) might be useful for detecting less severe types of myocardial injury (i.e., non-ST segment elevation myocardial infarction). The objective of this study is to elucidate the usefulness of (201)thallous chloride ((201)TlCl) and (123)I-betamethyl-p-iodophenyl-pentadecanoic acid ((123)I-BMIPP) dual-single-photon emission computed tomography (SPECT) imaging for patients with myocardial infarction (MI) without ST segment elevation. METHODS: Consecutive 86 patients (56 men and 30 women; mean age 66 +/- 12 years) clinically diagnosed with acute myocardial infarction (AMI) were divided into two groups according to serum creatine kinase MB (CK-MB) and cTnT levels. Group A consisted of 53 patients with increased serum CK-MB and cTnT levels, and Group B, 33 patients with increased serum cTnT without increased serum CK-MB. All patients underwent (201)TlCl and (123)I-BMIPP dual-SPECT about 8 days following the onset. The left ventricular myocardium was divided into 20 segments on each SPECT image, and tracer accumulation in those segments was scored on a five-point scoring system. The total defect scores (TDS) were calculated by summing the scores for all 20 segments, and compared between groups A and B. Group B patients were subdivided into two groups according to the TDS on (123)I-BMIPP images as groups B(S) (severe; TDS > or = 8) and B(M) (mild; TDS < or = 7), and we compared the prognosis over a period of 2 years from the onset between the three groups. RESULTS: The TDS of group A derived from (201)TlCl and (123)I-BMIPP images was significantly higher than those of group B (14.5 +/- 10.8 vs. 1.5 +/- 2.4 and 20.8 +/- 13.3 vs. 9.1 +/- 6.2, respectively; P < 0.0001). The sensitivities of (201)TlCl and (123)I-BMIPP images were 94.3% (50/53) and 96.2% (51/53) to detect the culprit coronary lesions in group A (no significant difference). In contrast, the sensitivity of (123)I-BMIPP images (72.7%, 24/33) was higher than that of (201)TlCl images (27.3%, 9/33) in group B (P < 0.05). At 2 years of follow-up, the incidence of hard cardiac events in groups A, B(S), and B(M) was 24.5%, 27.8%, and 6.7%, respectively. The rate of group BS, as well as that of group A, was significantly higher than that of group B(M) (P < 0.05). CONCLUSIONS: Of those with a clinical diagnosis of AMI accompanied by increased cTnT, the CK-MB negative patients accounted for 38% (33/86) of all patients as having non-ST segment elevation myocardial infarction such as NTMI. For such patients, (123)I-BMIPP imaging is useful not only for the detection of the culprit lesions but also for the prediction of the prognosis.     

Reproducibility of [<Superscript>123</Superscript>I]PE2I binding to dopamine transporters with SPECT

Purpose The iodinated cocaine derivative [¹²³I]PE2I is a new selective ligand for in vivo studies of the dopamine transporter (DAT) with SPECT. Recently, a bolus/infusion (B/I) protocol for [¹²³I]PE2I measurements of DAT density was established [Pinborg LH et al. J Nucl Med 2005;46:1119–271]. The aims of this study were, firstly, to evaluate the test–retest variability using the B/I protocol and, secondly, to evaluate the B/I approach in a new group of healthy subjects using two outcome parameters, BP₁ (C_ROI/C_plasma) and BP₂ (C_ROI/C_REF). Methods Seven healthy subjects were subjected to [¹²³I]PE2I SPECT scanning twice. For both studies, the two outcome parameters BP₁ and BP₂ were calculated based on two different methods for region of interest (ROI) delineation, namely manual delineation and probability map-based automatic delineation with MRI co-registration. Results With manual delineation, striatal test–retest variability (absolute difference between first and second scan as a percentage of the mean) of BP₁ and BP₂ was 13.9% (range 1.8–35.7%) and 4.1% (range 0.5–9.7%) respectively. The probability map-based automatic delineation resulted in striatal test–retest variability of 17.2% (range 4.3–40.5%) and 5.2% (range 0.1–10.9%) respectively. The B/I approach provided stable brain activity from 120 to 180 min post injection in both high- and low-count regions with a mean % change/hour in striatal BP₂ of 10.6. Conclusion [¹²³I]PE2I SPECT with the B/I approach yields a highly reproducible measure of striatal dopamine transporter binding. The appropriateness of a B/I protocol with a B/I ratio of 2.7 h (i.e. with a bolus worth 2.7 h of infusion) was confirmed in an independent sample of healthy subjects.     

Dopamine transporter density of basal ganglia assessed with [<Superscript>123</Superscript>I]IPT SPET in obsessive-compulsive disorder

It has been suggested that dopamine, as well as serotonin, is associated with the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies have been performed on brain regions associated with dopamine in patients with OCD. In the present study, we investigated the DAT density of the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2-carbomethoxy-3-(4-chlorophenyl) tropane ([¹²³I]IPT) single-photon emission tomography (SPET) and evaluated the activity of the presynaptic dopamine function in patients with OCD. Fifteen patients with OCD and 19 normal control adults were included in the study. We performed brain SPET 2 h after the intravenous administration of [¹²³I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific dopamine transporter (DAT) binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia. Compared with normal control adults, patients with OCD showed a significantly increased specific/non-specific DAT binding ratio in the right basal ganglia and a tendency towards an increased specific/non-specific DAT binding ratio in the left basal ganglia. No significant correlation was found between the total scores on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia in patients with OCD could be involved in the pathophysiology of OCD.     

Two phase imaging of<Superscript>99m</Superscript>Tc-SESTAMIBI and<Superscript>123</Superscript>I-BMIPP for patients with angina pectoris

We saw three cases of angina pectoris in which 99mTc-SESTAMIBI delayed images at rest were useful in diagnosing ischemia risk areas. These findings indicated that delayed 99mTc-SESTAMIBI images may be more sensitive to slight ischemia than 123I-BMIPP images, and suggested that imaging with 99mTc-SESTAMIBI twice at rest may be more effective. The addition of 123I-BMIPP SPECT was considered to be useful in making an evaluation of the severity of ischemia.     

Evaluation of cerebral perfusion in patients with neuropsychiatric systemic lupus erythematosus using <Superscript>123</Superscript>I-IMP SPECT

Objective In the course of systemic lupus erythematosus (SLE), central nervous system (CNS) complications occur at a high frequency. An accurate diagnosis of CNS lupus, differentiated from secondary CNS involvement, is difficult. CNS lupus is indicative of advancing primary disease and is treated by steroid pulse therapy or increased dosage of steroids. In contrast, if symptoms are caused by secondary CNS complications, it is possible to observe or treat these complications using symptomatic therapy. We examined whether quantitative cerebral blood flow (CBF) measured using cerebral perfusion single photon emission computed tomography (SPECT) can be used to differentiate CNS lupus from secondary CNS involvement. Methods We divided 18 SLE patients with CNS symptoms into a CNS lupus group and a non-CNS lupus group, and then compared the mean cerebral blood flow (mCBF) of each group of patients. SPECT was performed with N-isopropyl-p-[¹²³I] iodoamphetamine (IMP), with quantitation carried out by table look-up and autoradiographic methods. Results The mCBF of both groups was decreased; however, the mCBF of patients with CNS lupus was significantly lower than that of non-CNS lupus patients. Conclusion Quantitative CBF may provide a useful tool to distinguish CNS lupus from non-CNS lupus.     

Effects of anesthetic agents on cellular <Superscript>123</Superscript>I-MIBG transport and in vivo <Superscript>123</Superscript>I-MIBG biodistribution

Objectives Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution. Methods SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for ¹²³I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with ¹²³I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed. Results Cellular ¹²³I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 μM Ke, Xy, and Ke/Xy decreased uptake to 46.0 ± 1.6, 24.8 ± 1.5, and 18.3 ± 1.6% of controls. This effect was completely reversed by fresh media, and there was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ uptake. Conclusion In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG. Bong-Ho Ko and Jin-Young Paik equally contributed to this work. This work was supported by the Korea Research Foundation Grant KRF-2005-202-E00116. Presented in part at the fifth Annual Meeting of the Society for Molecular Imaging, Hawaii, August 30–September 2, 2006.     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Prediction of cardiac events in patients with dilated cardiomyopathy using <Superscript>123</Superscript>I-BMIPP and <Superscript>201</Superscript>Tl myocardial scintigraphy

Objective Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, ¹²³I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using ¹²³I-BMIPP and ²⁰¹TI (Tl) myocardial scintigraphy. Methods Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. Results The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 × 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (χ² test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). Conclusions These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.     

The dopamine D<Subscript>2</Subscript> receptor ligand <Superscript>18</Superscript>F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinsons disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D₂ receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D₂ receptor antagonist fluorine-18 desmethoxyfallypride (¹⁸F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180–200 MBq ¹⁸F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of ¹⁸F-DMFP PET. We found the striatal ¹⁸F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44±0.42) compared with the healthy control subjects (3.61±0.43) and the IPS patients (3.21±0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate ¹⁸F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider ¹⁸F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than ¹¹C-labelled D₂ radioligands.     

<Superscript>123</Superscript>I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after rotational atherectomy

Background During rotational atherectomy (RA), the coronary atherosclerotic plaque is largely pulverized into microdebris, which may cause serious hemodynamic instability owing to significant segmental left ventricular asynergy embolization of the distal microvasculature by atheromatous debris and associated vasospasm. Objective To evaluate the usefulness of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) in the examination of microvascular embolization after RA. Methods and results Nineteen patients with stable effort angina pectoris who had undergone RA were evaluated in this study. Left ventricular ejection fraction (LVEF) was determined by left ventriculography immediately before and after RA. The serum concentration of creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CPK-MB) isozyme, and cardiac troponin-T was determined after RA. ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) and ¹²³I-MIBG scintigraphic examinations were also performed 1 day after RA. The regional defect score (RDS) was determined from ^99mTc-MIBI scintigraphic findings, while early and delayed RDS, heart-to-mediastinum count ratios (H/M ratios), and washout rate (WR) were determined from ¹²³I-MIBG scintigraphy. After RA, the left ventriculographic LVEF mildly decreased by ≤10% in ten patients (group A), but it decreased by >10% in the remaining nine patients (group B). There were no differences in baseline clinical characteristics between the two groups. The CPK, CPK-MB isozyme, troponin-T, RDS by ^99mTc-MIBI, H/M ratios, and WR after RA were similar in the two groups. However, the RDSs determined from early and delayed ¹²³I-MIBG in group A were significantly lower than those in group B (4.5 ± 3.8 vs. 13.4 ± 10.8, P < 0.05; 9.0 ± 6.3 vs. 17.7 ± 10.0, P < 0.05, respectively). Moreover, there were significant correlations between delta LVEF and troponin-T (r = 0.54, P < 0.05) and RDSs of early and delayed ¹²³I-MIBG (r = 0.46, P < 0.05; r = 0.64, P < 0.05, respectively). Conclusions These findings suggest that ¹²³I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after RA.     

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.     

Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

Background [¹²³I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([¹²³I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Discussion Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [¹²³I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient’s care and taking into account the pros and cons of doing so.     

Homocysteine levels are associated with the results of <Superscript>123</Superscript>I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

Purpose Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. Methods The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58±5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels (≤15 mmol/l, age 58±9 years, normal tHcy group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy. Results Early and delayed ¹²³I-MIBG myocardial uptake values were lower (p<0.005 and p<0.01, respectively) and the percent washout rate of ¹²³I-MIBG was higher (p<0.001) in the high tHcy group than in the normal tHcy group. The fasting plasma insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index values (p<0.0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis revealed that the level of tHcy was independently predicted by the HOMA index values and the myocardial uptake of ¹²³I-MIBG at the delayed phase. Conclusion Our results demonstrate that high levels of tHcy are associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus.     

New semiquantitative assessment of123I-FP-CIT by an anatomical standardization method

We evaluated a new semiquantitative procedure to more easily and objectively estimate the striatal uptake of 123I-FP-CIT in patients with Parkinsonian syndrome (PS) and essential tremor (ET), using an anatomical standardization method, the Neurostat. METHODS: Eleven patients with PS and 8 with ET were examined by clinical assessment and 123I-FP-CIT SPECT imaging. The modified Hoehn and Yahr Staging Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess the stage and severity of the disease. The co-registered MR and SPECT images were created with fusion software included in Neurostat. On the cross section, which shows the largest area of striate, irregular shaped regions of interest corresponding to the striate and occipital cortex were drawn. Then the ratio of specific striatal uptake to non-specific occipital cortex, V3"(F), was calculated. Another calculation was done by VOIClassic, which is a software included in Neurostat to estimate the counts per voxel of anatomically defined regions such as caudate nucleus, putamen, occipital cortex, and total cortex. Using these count data, the ratio of specific striatal uptake to non-specific occipital cortex, V3"(OC), and total cortex, V3"(TC), was calculated. RESULTS: A fair linear correlation was observed between V3"(OC) and V3"(F) (y = 1.53x + 1.40; r = 0.756; p < 0.01), as well as between V3"(TC) and V3"(F) (y = 1.24x + 1.43; r = 0.713; p < 0.01). Both V3"(OC) and V3"(TC) yielded similar tendencies. Concerning discrimination between ET and PS, there was a significant difference between the mean V3" of PS and ET (p < 0.01). Concerning the correlation between V3" value and the severity of PS, the UPDRS motor score significantly correlated with the V3"(F) value (rs = -0.816). However, V3"(OC) and V3"(TC) correlated less with UPDRS (rs = -0.667 and -0.645, respectively). CONCLUSIONS: Semiquantitative parameters, V3"(OC) and V3"(TC), calculated by VOIClassic including the Neurostat system are useful and easily calculable parameters as well as V3"(F) for the differential diagnosis of PS from ET.     

Increasing myocardial<Superscript>123</Superscript>I-BMIPP uptake in non-ischemic area in a patient with acute myocardial ischemia

The subject was a 65-year-old woman with chest pain. An electrocardiogram revealed T-wave-inversion in leads III, aVF, V1-V5. 99mTc-tetrofosmin myocardial SPECT showed mildly reduced uptake in the anteroseptal wall and the apex. These findings suggested acute myocardial ischemia. Coronary angiography did not show any stenotic lesions, but diffuse coronary ectasia was noted in three vessels. Coronary flow velocity was remarkably reduced on coronary angiography. Epicardial coronary spasm was not provoked by ergonovine loading test. Left ventriculography showed diffuse hypokinesis. 123I-BMIPP myocardial SPECT showed mildly reduced uptake in the anteroseptal wall and the apex on the early images. But 4-hour delayed images showed an increase of 8% in myocardial 123I-BMIPP uptake. We treated this patient with ticlopidine and nicorandil. After drug therapy her symptoms and left ventriculography improved. 123I-BMIPP myocardial SPECT findings on the early images improved, whereas delayed images showed a decrease of 28% in myocardial 123I-BMIPP uptake after two weeks and 36% after four weeks. These dynamic changes in 123I-BMIPP findings might be a reflection of myocardial fatty acid metabolism in patients with acute myocardial ischemia. Delayed 123I-BMIPP myocardial SPECT images are useful for the assessment of fatty acid metabolism.     

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by<Superscript>123</Superscript>I-BMIPP SPECT and<Superscript>99m</Superscript>Tc-tetrofosmin electrocardiographically gated SPECT

Objective: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).Methods: Thirty-nine patients with cardiomyopathies (58±14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with¹²³I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and^99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis.Results: BMIPP uptake was decreased (p<0.05), and its washout was increased (p<0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p>0.05), but showed a significant correlation with H/M-TF (p<0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p<0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p>0.05) but had a significant correlation with regional perfusion (p<0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p<0.005) and perfusion (p<0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively.Conclusion: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.     

Incremental predictive value of myocardial scintigraphy with<Superscript> 123</Superscript>I-BMIPP in patients with acute myocardial infarction treated with primary percutaneous coronary intervention

Purpose It is unclear whether ¹²³I-labelled -methyl iodophenyl pentadecanoic acid (¹²³I-BMIPP) myocardial scintigraphy adds further predictive value for future cardiac events compared with the variables obtained during cardiac catheterisation in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). We therefore investigated whether ¹²³I-BMIPP imaging in patients with AMI treated by primary PCI was useful in predicting future cardiac events.Methods One hundred and fifty-nine patients with AMI who were treated with primary PCI and underwent left ventriculography (LVG) on admission underwent ²⁰¹Tl and ¹²³I-BMIPP myocardial scintigraphy. Scintigrams were visually classified, and the total defect score (TDS) was calculated. Major adverse cardiac events (MACE) were defined as cardiac death including sudden death, congestive heart failure and recurrence of acute coronary syndrome. Patients were followed up for a mean of 34.5 months (12–63 months).Results Twenty-six patients had MACE. Kaplan-Meier analysis indicated that patients with the top 50% of ¹²³I-BMIPP TDSs had a significantly higher rate of MACE (P=0.007). Patients with mismatch between ²⁰¹Tl and ¹²³I-BMIPP images also had significantly more MACE (P=0.02). In the prediction of MACE, the global chi-square value was 5.2 (P=0.001) based on LVEF (<45%) and the number of diseased vessels (two or three). Adding ¹²³I-BMIPP TDS and the mismatch improved the global chi-square value ( ²=7.2)Conclusion Myocardial scintigraphy using ²⁰¹Tl and ¹²³I-BMIPP predicts future cardiac events in patients with AMI treated with primary PCI, and provides additional predictive value compared with the variables obtained with cardiac catheterisation alone.     

<Superscript>123</Superscript>I-FP-CIT SPECT findings and its clinical relevance in prodromal dementia with Lewy bodies

Purpose

Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the ¹²³I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance.

Methods

We enrolled subjects into a prodromal DLB group (PRD-DLB) (n?=?20) and clinical DLB group (CLIN-DLB) (n?=?18) and compared these groups with an Alzheimer’s disease control group (AD) (n?=?10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in ¹⁸F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of ¹²³I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups.

Results

Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB.

Conclusion

¹²³I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.