Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy.

OBJECT: The aim in this study was to present long-term results regarding overall survival (OS), adverse effects, and toxicity following fractionated intracavitary radioimmunotherapy (RIT) with iodine-131- or yttrium-90-labeled anti-tenascin monoclonal antibody ((131)I-mAB or (90)Y-mAB) for the treatment of patients with malignant glioma. METHODS: In 55 patients (15 patients with WHO Grade III anaplastic astrocytoma [AA] and 40 patients with WHO Grade IV glioblastoma multiforme [GBM]) following tumor resection and conventional radiotherapy, radioimmunoconjugate was introduced into the postoperative resection cavity. Patients received 5 cycles of (90)Y-mAB (Group A, average dose 18 mCi/cycle), 5 cycles of (131)I-mAB (Group B, average dose 30 mCi/cycle), or 3 cycles of (131)I-mAB (Group C, 50, 40, and 30 mCi). RESULTS: Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8-25.3), and median OS was 25.3 months (95% CI18-30) forthose patients treated with the (131)I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responding well to steroids. CONCLUSIONS: Median OS of GBM and AA patients treated with (131)I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeding that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen.

Nigrostriatal dopamine terminal imaging with dopamine transporter SPECT: an update.

This article gives an update on nigrostriatal dopamine terminal imaging, with emphasis on SPECT performed with the presynaptic dopamine transporter (DAT) ligand (123)I-FP-CIT. The paper covers the rational use of this technique in the diagnostic work-up of patients with known or suspected parkinsonian syndromes. In detail, it addresses the impact of the method for the proof or exclusion of neurodegenerative parkinsonism, for its early and preclinical diagnosis, and for the evaluation of disease progression. The importance of normal DAT binding for differentiating symptomatic parkinsonism and relevant tremor syndromes from neurodegeneration is highlighted. Particularly emphasized is the role of DAT SPECT for diagnosing Lewy body dementia and its separation from Alzheimer dementia. Finally, some remarks deal with the economic aspects of the use of these imaging techniques in the clinical setting.

Mid-term results in otherwise treatment refractory primary or secondary liver confined tumours treated with selective internal radiation therapy (SIRT) using (90)Yttrium resin-microspheres.

The purpose was to determine the response and survival and to analyse the feasibility of single-session, whole-liver SIRT in patients with non-resectable, otherwise non-responding liver cancer. Thirty-nine patients qualified for SIRT. Eighteen patients suffered from colorectal-cancer metastases (CRC), breast-cancer metastases (MBC, 7), HCC (5) and other tumours (9). Response was assessed by tumour-markers and CT-imaging. At 2-4, 5-7 and 8-9 months follow-up in 3/17, 5/15 and 5/10 of CRC-patients CEA-levels were higher than before. In the MBC group 1-3 and 4-6 months after SIRT tumour-marker-levels were higher in 2/6 and 3/3 patients, respectively. In all HCC-patients AFP-levels dropped 1-3 months after SIRT. Using RECIST, in the CRC-group progressive liver disease (PD) was found in 4/17, 2/12, 2/10 and 2/5 patients at 2-4, 5-8, 9-10 and 12-14 months follow-up. Concerning MBC, after 3 months 7/7 patients presented with stable-disease (SD) or partial-response (PR). At 5-6 months, 1/5 patients showed PD. All HCC-patients showed SD/PR at 2-3 months with no PD at 5-8 months. In the mixed-group 5/6 patients presented with SD/PR at 3-4 months and with SD in 2/3 patients at 5-6 months. The median time-to-PD was 6.5, 8.5 and 8 months for the CRC-, MBC- and mixed-group, respectively. SIRT is a promising, liver-targeted approach for patients with otherwise treatment-refractory liver tumours.

SERT and DAT availabilities under citalopram treatment in obsessive-compulsive disorder (OCD).

Serotonin and dopamine transporter (SERT, DAT) availabilities have prospectively been investigated using [123I]beta-CIT and single photon emission computed tomography in subjects with obsessive-compulsive disorder under treatment with the selective serotonin reuptake inhibitor citalopram. SERT availability decreased by a mean 36.5%, whereas DAT availability increased by about 40%. The data point at a citalopram induced modulation of both serotonergic and dopaminergic activity and support the notion of functional interactions of monoaminergic systems in the human brain.

Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically induced disconnection in CADASIL: an 18F-FDG PET study.

UNLABELLED: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic lesions are largely confined to subcortical structures, whereas the cortex is spared. CADASIL, therefore, may serve as a model to study subcortically induced remote effects. The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection. METHODS: Eleven CADASIL patients (7 women, 4 men; mean age, 55.8 +/- 6.7 y) without cortical lesions on brain MR images underwent PET after intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according to a previously published method. For further processing, patient studies were registered to a template of a healthy control group and region-of-interest-based and voxelwise comparisons were performed. RESULTS: In CADASIL patients, mean rCMRglc was significantly reduced in all cortical and subcortical structures, compared with the values in healthy volunteers. In the subcortical gray matter, metabolic rates, given as the percentage of the mean of healthy volunteers, were 49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively. Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the frontal, parietal, temporal, and occipital lobes, respectively. On an individual level, most patients showed marked asymmetry and inhomogeneities of cortical glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed cerebellar diaschisis. CONCLUSION: This study showed that cortical glucose metabolism is significantly lower in CADASIL patients than in healthy volunteers. The observed decrease in rCMRglc may in part be explained by a reduction of cerebral blood flow and neuronal loss. In addition, our data provide evidence of remote effects secondary to the functional disruption of subcortical fiber tracts in this particular type of small-vessel disease.