Clinical usefulness of iodine-123-MIBG scintigraphy for patients with neuroblastoma detected by a mass screening survey

The purpose of this study was to evaluate the usefulness in a clinical setting of iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy, planar and single photon emission computed tomography (SPECT) images, in patients with neuroblastoma as detected by a mass screening survey. METHODS: 123I-MIBG planar whole body images, and regional SPECT images of patients with neuroblastoma in 51 studies were reviewed. They were all detected by a mass screening survey performed in the 6th month after birth using vanil mandelic acid (VMA), and homovanillic acid (HVA) and the neuroblastoma had been confirmed by surgery. Scintigraphy was performed 24 hours after injection of 111 MBq of 123I-MIBG. We assessed the accuracy of the planar whole body images in order to demonstrate the extent of the lesion and the correlation between the degree and extent of the lesions of 123I-MIBG accumulation and clinical staging with tumor markers, such as urinary VMA, urinary HVA, serum neuron specific enolase (NSE) and serum lactate dehydrogenase (LDH). Additionally, we evaluated SPECT how useful supplemental SPECT might be in a clinical setting as compared with planar whole body images. RESULTS: 123I-MIBG planar whole body images revealed all 33 (100%) primary lesions, 4 of the 5 cases (80%) with liver metastasis, 3 of the 13 (23%) with lymph nodes metastasis and 1 of 3 (33%) with bone marrow infiltration. The extent and degree of accumulation correlated with the values of urinary VMA, urinary HVA and serum NSE. SPECT images helped to understand the positional relation in all cases and provided useful additional information for clinical staging in 7 cases. CONCLUSION: 123I-MIBG scintigraphy with planar and SPECT images is useful for evaluating patients with neuroblastoma, following detection by a mass screening survey.     

Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT4 receptors with SPET

Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT₄) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT₄ receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT₄ receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT₄ receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [¹²³I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT₄ receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT₄ receptor antagonist, SB 204070, at 20 min before [¹²³I]SB 207710 injection. Radioactivity in all brain regions was reduced almost to the level in cerebellum by 176 min after radioligand injection. These findings show that [¹²³I]SB 207710 is an effective radioligand for imaging brain 5-HT₄ receptors in vivo.For preliminary accounts of this work, see Pike VW et al., J Nucl Med 1998; 39 (Suppl):185; Eur J Nucl Med 1999; 26:991.     

ETA receptor-mediated Ca2+ mobilisation in H9c2 cardiac cells

Expression and pharmacological properties of endothelin receptors (ETRs) were investigated in H9c2 cardiomyoblasts. The mechanism of receptor-mediated modulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) was examined by measuring fluorescence increase of Fluo-3-loaded cells with flow cytometry. Binding assays showed that [125I]endothelin-1 (ET-1) bound to a single class of high affinity binding sites in cardiomyoblast membranes. Endothelin-3 (ET-3) displaced bound [125I]ET-1 in a biphasic manner, in contrast to an ET(B)-selective agonist, IRL-1620, that was ineffective. The ET(B)-selective antagonist, BQ-788, inhibited [125I]ET-1 binding in a monophasic manner and with low potency. An ET(A)-selective antagonist, BQ-123, competed [125I]ET-1 binding in a monophasic manner. This antagonist was found to be 13-fold more potent than BQ-788. Immunoblotting analysis using anti-ET(A) and -ET(B) antibodies confirmed a predominant expression of the ET(A) receptor. ET-1 induced a concentration-dependent increase of Fluo-3 fluorescence in cardiomyoblasts resuspended in buffer containing 1mM CaCl(2). Treatment of cells with antagonists, PD-145065 and BQ-123, or a phospholipase C-beta inhibitor, U-73122, abolished ET-1-mediated increases in fluorescence. The close structural analogue of U-73122, U-73343, caused a minimal effect on the concentration-response curve of ET-1. ET-3 produced no major increase of Fluo-3 fluorescence. Removal of extracellular Ca(2+) resulted in a shift to the right of the ET-1 concentration-response curve. Both the L-type voltage-operated Ca(2+) channel blocker, nifedipine, and the ryanodine receptor inhibitor, dantrolene, reduced the efficacy of ET-1. Two protein kinase C inhibitors reduced both potency and efficacy of ET-1. Our results demonstrate that ET(A) receptors are expressed and functionally coupled to rise of [Ca(2+)](i) in H9c2 cardiomyoblasts. ET-1-induced [Ca(2+)](i) increase is triggered by Ca(2+) release from intracellular inositol 1,4,5-trisphosphate-gated stores; plasma membrane Ca(2+) channels and ryanodine receptors participate in sustaining the Ca(2+) response. Regulation of channel opening by protein kinase C is also involved in the process of [Ca(2+)](i) increase.     

Regional serotonin transporter availability and depression are correlated in Wilson’s disease

Summary. In patients with Wilsons disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [¹²³I]-2-carbomethoxy-3-(iodophenyl)tropane ([¹²³I]-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [¹²³I]-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients.Received December 10, 2001; accepted March 24, 2003 Published online June 10, 2003     

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease

Objective: One of the most frequent psychiatric symptoms in patients with Wilson's disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. Methods: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus–hypothalamus and the midbrain–pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2β-carbomethoxy-3β-(4 [¹²³I]iodophenyl)tropane ( [¹²³I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. Results: A significant negative correlation was found between HAMD and SERT density in the thalamus–hypothalamus region (r = −0.49, p = 0.02), but not in the midbrain–pons (r = −0.31, p = 0.15). Conclusions: We conclude that depression in patients with Wilson's disease is correlated with alterations of serotonergic neurotransmission in the thalamus–hypothalamus region. Received: 24 July 2002, Received in revised form: 20 November 2002, Accepted: 28 November 2002 Correspondence to Wieland Hermanns, MD     

Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study

RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine.     

内皮素及其A受体在兔颅脑创伤后脑血流量变化中的作用及意义

目的:了解内皮素(ET)及其A受体在颅脑创伤后脑血流量变化中的作用及意义.方法:130只家兔致以左额顶叶为着力部位的加速性撞击伤,动态观察脑组织内皮素含量变化、内皮素A受体mRNA表达和定位变化,内皮素A受体拮抗剂BQ123的作用及上述变化对脑血流量变化的影响.结果:脑创伤后血浆、脑脊液和局部脑组织内皮素含量显著升高;内皮素A受体mRNA主要分布于脑血管内皮细胞,表达显著增强;创伤后局部脑血流量显著降低,应用BQ123治疗的动物,血流量下降被明显抑制.结论:内皮素通过其A受体的调节在颅脑创伤后脑缺血的形成中有重要作用;应用内皮素A受体拮抗剂可以防治颅脑创伤后脑缺血.     

种植材料生物学特性对牙种植体生物相容性的影响

牙种植体材料主要分为：钛及其合金、生物活性陶瓷、碳和高分子材料。文章从这几种材料的生物学特性入手，介绍了这几种材料的优点及存在的问题；探讨了种植体表面形态、种植体的长度和直径对应力分布的影响；证实了种植体表面的涂层、种植体的生物力学对种植体材料的生物相容性都发挥着不同程度的作用。     

Effects of cigarette smoking on iodine 123 N-isopropyl-p-iodoamphetamine clearance from the lung

Iodine 123 N-isopropyl p-iodoamphetamine (¹²³I-IMP), originally developed as a brain scanning agent, is also taken up by the lung. To evaluate the effects of cigarette smoking on the kinetics of IMP in the lung, we studied ¹²³I-IMP clearance from the lung in 18 volunteers (8 non-smokers and 10 smokers). After the injection of 111 MBq of ¹²³I-IMP into the medial cubital vein, the time-activity curve for 60 min and the regional activity using 1 frame per minute and a 64 × 64 matrix were obtained. The ¹²³I-IMP clearance curve was described as follows: C (t) = A ₁e^–k ₁ t+ A ₂e^–k ₂ t (A1, A ₂: intercepts, and k ₁, k ₂: slopes of the exponential components). ¹²³I-IMP clearance was delayed in smokers, and k ₂ was smaller in smokers. Also, a correlation between k ₁, k ₂, and the number of cigarettes smoked per day was found (r = –0.65, r = –0.74, respectively, P<0.01). In conclusion, this study suggests that the delayed clearance and retention of ¹²³I-IMP in the lung indicate lung metabolic disorders due to cigarette smoking.Offprint requests to: K. Kato     

193 nm氟化氩激光应用于屈光性角膜切削的精确性及预测性

1975年有学者发现了准分子激光并将它应用于角膜屈光性手术，使屈光手术有了重大突破，成为现代眼科学中发展最快的领域之一。波长为193 nm的氟化氩激光可以使角膜组织分子气化，故准确度非常高，而且对于被照射部位旁边的组织不产生热效应，对角膜的构造不会产生不良的效应。目前准分子激光已成功应用于角膜放射状切开术、准分子激光屈光角膜切削术、准分子激光原位角膜磨镶术、准分子激光角膜上皮瓣下磨镶术及机械法准分子上皮下角膜磨镶术等。随着对准分子激光认识的不断深入，以及临床经验的不断积累，新的、精确度高的、预测性好的准分子激光屈光性角膜手术方式将不断涌现。