Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine

Purpose

⁶⁸Ga-DOTA-Tyr³-octreotide positron emission tomography (⁶⁸Ga-DOTA-TOC PET) has proven to be superior to ¹¹¹In-DTPA-D-Phe¹-octreotide (¹¹¹In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard.

Methods

Three male and eight female patients (age range 3 to 68?years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with ⁶⁸Ga-DOTA-TOC?PET and ¹²³I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis.

Results

On a per-patient basis, both ⁶⁸Ga-DOTA-TOC and ¹²³I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of ⁶⁸Ga-DOTA-TOC was 91.7% and that of ¹²³I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of ⁶⁸Ga-DOTA-TOC was 97.2% and that of ¹²³I-MIBG was 90.7%. Overall, in this patient cohort, ⁶⁸Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and ¹²³I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of ⁶⁸Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of ¹²³I-MIBG was 76.9% (McNemar p<0.0001).

Conclusion

Our analysis in this relatively small patient cohort indicates that ⁶⁸Ga-DOTA-TOC PET may be superior to ¹²³I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.     

Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents.

BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance-abuse disorders. Studies in nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (BOLD) responses in these regions during functional magnetic resonance imaging (fMRI) paradigms; however, no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related fMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in psychiatrically healthy children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum and lateral and medial orbital-frontal cortex; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related fMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth.     

Homocysteine and serum markers of immune activation in primary dystonia.

The cause of primary dystonia remains unknown. Several reports point to immune system disturbances in primary dystonia and a recent study demonstrated hyperhomocysteinemia in cervical dystonia. Homocysteine (HCY) is an amino acid and elevated HCY concentrations were shown to be associated with immune system activation and increased neopterin serum concentrations. We examined HCY serum concentrations together with serum markers of immune activation in patients with different types of primary dystonia. Eighty-three patients with different types of primary dystonia were included and investigated at least 3 months following botulinum toxin treatment. Thirty-six healthy volunteers with similar age and sex distribution served as controls. Total serum HCY, kynurenine, and tryptophan concentrations were determined by high-performance liquid chromatography; neopterin, folate, and vitamin B12 concentrations were measured by immunoassays. Routine blood analysis, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood count (WBC), was performed. Patients with primary dystonia had significantly higher HCY concentrations compared to controls. Among the dystonia subtypes, no significant difference of HCY serum concentrations was observed. CRP and ESR were within the normal range in >90% of the patients and all had normal WBC. Neopterin, kynurenine, and tryptophan serum concentrations were similar in patients and controls and not correlated with HCY serum concentrations. The results provide evidence against enhanced cellular immune activation in patients with primary dystonia. However, hyperhomocysteinemia was present in all dystonia subtypes and unrelated to immune activation in this study. HCY is a neuronal excitotoxic amino acid and hyperhomocysteinemia is considered an independent vascular risk factor. Further studies are required to define the background of hyperhomocysteinemia in primary dystonia.     

Synthesis and pharmacological study of new N-methyl 1,2,3-triazole derivatives of 2-cyano chromones

The reaction of various 2-cyano chromones with diazomethane generated a series of 21 N-methyl triazoles, with a benzopyrone moiety and divided into three isomeric groups. The anti-inflammatory, psychotropic and anti-allergic effects of these new compounds were evaluated. The results obtained did not confirm their expected potentialities.     

The role of endothelial nitric oxide synthase (eNOS) genetic variants in European patients with intracranial aneurysms.

The endothelial nitric oxide synthase (eNOS) gene harbors three well-characterized genetic variants, which have been reported to be associated with various vascular diseases. Recently, conflicting results have been published relating to the role of these genetic variants in the pathogenesis of intracranial aneurysms (IA). Therefore, we analyzed these variants in a large European population of IA patients and controls. In all, 142 patients with IA and 190 controls were enrolled in our study. The -786T>C and 894G>T single-nucleotide polymorphisms (SNPs) were analyzed by direct sequencing of the corresponding sections in the genomic DNA. A variable number tandem repeat (VNTR) located in intron 4 of the gene and consisting of either four or five 27-base pair (bp) repeats was analyzed by polymerase chain reaction amplification and electrophoresis using ALF sequencertrade mark equipment. Genotype and allele frequencies were determined, and the frequencies in cases and controls were compared. In addition, haplotypes were constructed. There were no deviations from Hardy-Weinberg equilibrium. Genotype and allele frequencies did not differ significantly between cases and controls in any sample group or after stratification for multiple IA or aneurysm size. No single haplotype was significantly associated with the phenotype of an IA. The -786T>C, 894G>T, and 27-bp VNTR genetic variants of the eNOS gene are not associated with IA in the European population.     

Indications for surgery in upper cervical spine injury

20% of all spine injuries are cervical spine injuries. Surgical treatment of these injuries must take into account the great mobility of this part of the spinal column. Therefore, biomechanical aspects must be considered, especially in the upper cervical spine — C1 and C2. Describing our own therapeutical regimen in 35 patients with unstable upper cervical spine injuries we explain the biomechanical background and review the literature. It becomes evident that ventral approaches are superior to dorsal techniques for decompression, reposition, and stabilization with minimal loss of mobility.     

1-Aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants

A series of 1-aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives were synthesized and evaluated as potential antidepressants. Compounds with the Z configuration were synthesized from 1-aryl-2-oxo-3-oxabicyclo[3.1.0]hexane and those with the E configuration from (E)-1-phenyl-2-(hydroxymethyl)cyclopropanecarboxylic acid. The compounds were evaluated in animal tests designed to reveal potential antidepressant activity and the existence of undesirable side effects. Several derivatives were more active than imipramine and desipramine. On the basis of its activity in pharmacological animal tests of antidepressant activity and its potential lack of side effects, 1-phenyl-1-[(diethylamino)carbonyl]-2- (aminomethyl)cyclopropane hydrochloride, midalcipran (INN), was selected for further development. This compound is currently in phase III clinical evaluation.     

Importance of response to neoadjuvant chemotherapy in potentially curable colorectal cancer liver metastases

Background  

Surgical resection of liver metastases arising from colorectal cancer is considered the only curative treatment option. However, many patients subsequently experience disease recurrence. We prospectively investigated whether neoadjuvant chemotherapy reduces the risk of recurrence following potentially curative liver resection. Special emphasis was directed to the importance of response.