Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time dispersion in acute myocardial infarction

lodine-123 metaiodobenzylguanidine (MIBG) uptake was reported to be reduced compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an area, degrees of both sympathetic neural function and ischemic myocardial cell damage are considered to be greatly dispersed. These kinds of damage were reported to effect reporalization time in myocardial cells, and we evaluated our hypothesis that extension of the discordant MIBG uptake area correlates with recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated in 9 segments of SPECT by using four-point scoring. The total score was the sum of scores in 9 SPECT segments. ATI-MIBG was calculated by subtracting the total MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal-averaged ECG. RTc dispersion was defined as the difference between maximal and minimal RTc. The patients were assigned to two groups (group A; < or = Lown 4a, group B; > or = Lown 4b) according to the results of 24-hour Holter monitoring. A positive correlation between RTc dispersion and ATI-MIBG was found. ATI-MIBG and RTc dispersion in group B were greater than those in group A. These results suggested that ATI-MIBG could be used to predict the development of malignant ventricular arrhythmias.     

Detection of denervated but viable myocardium in cardiac sarcoidosis with I-123 MIBG and Tl-201 SPECT imaging

A 58-year-old man, who had biopsy-proven cardiac sarcoidosis, underwent TI-201 and I-123 MIBG cardiac scintigraphy. Although no perfusion defect was identified by Tl-201, mild heterogeneity of I-123 MIBG uptake was present in the myocardium. The denervated but viable myocardium was demonstrated in the heart with sarcoidosis. Cardiac sympathetic nerve function was impaired in cardiac sarcoidosis, slightly improved with steroid therapy. I-123 MIBG scintigraphy may be useful to assess extent of myocardial involvement and response to therapy.     

Role of P-Glycoprotein in Ocular Clearance of Rhodamine 123 in Rabbits

Pharmaceutical Research -     

Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography

Iodine-123 metaiodobenzylguanidine (mIBG) is taken up by sympathetic nerve endings, allowing scintigraphic imaging of myocardial sympathetic innervation. We investigated the denervated but viable canine myocardium after acute myocardial infarction by serial mIBG and thallium-201 chloride (²⁰¹TIC1) single photon emission tomography (SPET). In 12 dogs, acute myocardial infarction was produced by ligation of the left circumflex coronary artery. Images of mIBG and thallium SPET were obtained 6 h, 1, 4 and 6 weeks later. The defect size was calculated in percentage points from short axial views, and the ¹²³I-mIBG/²⁰¹TlCl ratio was determined. The uptake ratio was high at 1 week but gradually decreased. Three dogs were killed at each time point, and tissue samples were obtained from infarcted (both ²⁰¹TICl and ¹²³I-mIBG defects), peri-infarcted (¹²³I-mIBG defect and ²⁰¹TICl normal) and normal myocardium (both mIBG and ²⁰¹TIC1 normal). The changes in tissue content of noradrenaline in these lesions were measured. Noradrenaline tissue content gradually recovered in the peri-infarcted area. However, no recovery was noted in the infarcted area at 6 weeks. We conclude that sympathetic denervation and re-innervation occur following acute myocardial infarction, and the denervated but viable myocardium could be detected non-invasively by combined mIBG and thallium SPET. Offprint requests to: T. Nishimura     

Dosimetry of iodine-123 iodobenzamide in healthy volunteers

The distribution of the dopamine D₂-receptor specific ligand iodine-123 (S)-(–)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl)methyl]-benzamide (1231-IBZM) was investigated in human adults from whole-body scans, blood samples and urine collected up to 48 h after injection. Results from the present study performed in six healthy volunteers were combined with those of five volunteers from a previous study. Using the brain, liver, lungs and spleen as source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The thyroid (despite blockage), gall-bladder wall, large intestinal walls and spleen received the highest absorbed doses. The average effective dose equivalent of ¹²³I-IBZM for adults was estimated to be 0.034 mSv/MBq. The absorbed dose to the thyroid may be a limiting factor for 1231-IBZM studies in children.     

Cis-trans position effect in cancer translocations

Translocations of chromosomes occurring in human cancer cells appear specific to the type of cell from which the cancer arises. To explain the action of these translocations, we propose dual position effect: Position effect of the cis type transforms the cell to malignancy, while position effect of the trans type permits the normal homologous chromosome to express a normal gene product. Thus, the translocation itself has to do with malignant transformation, while the normal homologous chromosome performs its normal function. This dual concept is illustrated by t(8;14) in Burkitt's lymphoma. The concept can be tested with t(2;18) and t(8;22) in lymphoid malignancies and with other translocations and chromosome rearrangements marking human cancer cells.     

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

Purpose The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [¹²³I]FP-CIT.Methods [¹²³I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [¹²³I]FP-CIT scans with bone metabolism and perfusion scans obtained with ^99mTc-DPD and ^99mTc-tetrofosmin, respectively. As these tracers do not pass the blood–brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [¹²³I]FP-CIT scans with images of brain perfusion obtained with ^99mTc-HMPAO.Results Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V₃) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (t test, two-tailed, p<0.0001). Cortical V₃ values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [¹²³I]FP-CIT accumulation.Conclusion The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [¹²³I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinsons and Huntingtons disease, may be feasible using SPECT radioligands and small animal imaging systems.     

Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: a SPECT validation study

Purpose Serotonergic brain regions play a crucial role in the modulation of emotion, and serotonergic dysfunction may contribute to several neurological disorders. [¹²³I]ADAM is a novel SPECT tracer which binds with high affinity to serotonin transporters (SERT). The objective of this study was to compare different methods for the quantification of tracer binding and to develop a simplified single-scan protocol for this tracer, as well as to investigate its potential for characterisation of the transporter occupancy versus plasma concentration curve of a selective serotonin re-uptake inhibitor (SSRI).Methods Dynamic SPECT scans were performed on 16 healthy volunteers after administration of 150 MBq [¹²³I]ADAM. Data were acquired from the time of injection until 5.5 h after injection in 30- or 45-min sessions. Each subject was scanned twice: with and without pre-treatment with the SSRI citalopram in various dosage regimens. The plasma concentration of citalopram (C_p) was determined from venous samples. Images were reconstructed by filtered back-projection with scatter and attenuation correction. Tracer binding was quantified for midbrain, striatum and thalamus using cerebellum as a reference region. Quantification was done by kinetic modelling, graphical analysis and multi-linear regression, as well as by the ratio method, with binding potential (BP₂) as the outcome measure. The SERT occupancy by citalopram was determined relative to the baseline scan for each subject, and the occupancy versus C_p curve was fitted with the E_max model.Results The highest binding of [¹²³I]ADAM was in midbrain (mean baseline BP₂±SD=1.31±0.29), with lower binding in thalamus (0.79±0.16) and striatum (0.66±0.13). There was good agreement between BP₂ values obtained by different quantification methods. Using the ratio method, the best agreement with kinetic modelling was obtained with data from the time interval [200,260] min after injection. The fitting of the midbrain occupancy curve yielded a maximum occupancy of 84% and a plasma concentration required to reach 50% of the maximum of 2.5 ng/ml, with a goodness-of-fit variability of 13% (SD).Conclusion Binding of [¹²³I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.     

Respiratory frequencies of sleeping infants during the first months of life: Correlations between values in different sleep states

This study was carried out on 57 normal infants: 22 full-term newborns, examined in the hospital laboratory, and 35 2–18-wk-old infants, examined in two resident nurseries. Polygraphic records, including 1–3 complete sleep cycles, were performed during the morning. The tracings were analyzed by 20-sec epochs.Three to 10% of active sleep states (AS) and 0.8-4% of quiet sleep states (QS) included ?3 sec respiratory pauses. There were minimal, non-significant differences between respiratory frequencies (RF) in total and in no-pause tracings.Our results confirmed that RF was higher in AS in all ages, when compared with QS (P < 0.02). During the transition (TS) from one to another well-defined sleep state, the respiratory rate showed an intermediate level (AS > TS > QS): the transition from AS to QS showed progressive slowing of RF, while the transition from QS to AS occurred abruptly, with sudden acceleration of RF. There was a significant slowing of RF during the course of QS, while the RF in AS was more variable without significant differences between the beginning, the middle and the end of AS state. In this material, RF was higher in 2–5-wk and 6–10-wk age groups, compared to newborns and to 11-18-wk-old infants. At all ages, there was a high degree of correlation (P < 0.01) between RF found in different sleep states for given individuals: some infants breathed more rapidly and others more slowly in all sleep states.A review of the literature showed that the differences between normal RF     

Imaging of dopamine transporters and D2 receptors in vascular parkinsonism: a report of four cases

Summary. The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism (VP) has been addressed by only few studies up to now. Most previous reports suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in four patients with VP, reported here, the combined DAT and D2 receptor SPECT showed highly unusual changes in the pre- and/or postsynaptic dopaminergic system. The possible value of combined DAT/D2 receptor SPECT imaging should be investigated by future prospective studies. These two authors contributed equally