Learning Objectives: On successful completion of this activity, participants should be able to describe (1) the radiopharmaceuticals used to evaluate nigrostriatal dopamine imaging; (2) the pattern of uptake of these radiopharmaceuticals in parkinsonian syndromes; and (3) the role of these radiopharmaceuticals in the evaluation of parkinsonian syndromes.Financial Disclosure: Dr. Tatsch is a meeting participant/lecturer for GE Healthcare. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, participants can access this activity through the SNMMI Web site (http:// www.snmmi.org/ce_online) through August 2016.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.
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.
abbreviatioNs AA = anaplastic astrocytoma; ALA = 5-aminolevulinic acid; CTC = Common Toxicity Criteria; GBM = glioblastoma multiforme; HR = hazard ratio; IDH1 = isocitrate dehydrogenase; KPS = Karnofsky Performance Scale; mAB = monoclonal antibody; MGMT = O 6 -methylguanine-DNA methyltransferase; OS = overall survival; RC = resection cavity; RIT = radioimmunotherapy; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group. submitted September 16, 2014. accepted December 12, 2014. iNclude wheN citiNg Published online July 3, 2015; DOI: 10.3171/2014.12.JNS142168. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. This work was supported by grants from the German research foundation DFG (GO998/1-1), the Deutsche Krebshilfe (10-1782-GO2), and a fund of the MMW Foundation (Verein zur Förder-ung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München e.V.). * Drs. Reulen and Poepperl contributed equally to this work. 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% CI 18-30) for those 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. Long
Schizophrenia is a complex dynamic disorder comprising a wide range of neurobiological alterations including dopaminergic dysfunction. The aim of the study was to investigate dynamic changes of dopaminergic neurotransmission in patients with schizophrenia (n=8, mean age 25.4 ± 5.8 years) in early stages of the disorder, compared to healthy control subjects (n=7, mean age 23.6 ± 2.7 years). A dynamic IBZM SPECT protocol was used to assess the endogenous dopamine release following an amphetamine challenge. Subjects received a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed 2 h after bolus injection, and 1 h following the amphetamine challenge (0.3 mg/kg). Striatal IBZM binding to dopamine D2 receptors was assessed with a volume-of-interest (VOI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. At baseline, patients showed higher mean striatal IBZM binding compared to controls (0.77 ± 0.09 vs. 0.68 ± 0.07, p=0.07). There was a statistically significant difference in IBZM binding between patients, with a predominance of negative vs. positive symptoms (0.84 ± 0.08 vs. 0.71 ± 0.04, p<0.05). Upon amphetamine challenge, mean IBZM binding decreased by about 4.9 ± 7.6% in controls (n=7) compared to a mean of 12.4 ± 5.8% in subjects with schizophrenia (p<0.05). In patients, paranoid symptoms showed a significant negative correlation with IBZM baseline binding, whereas there was a trend towards positive correlation with the decrease of IBZM binding under challenge. Negative symptoms showed positive associations with baseline IBZM binding. The data are in line with previous reports and contribute to the notion of a dynamic instability of the dopaminergic system in patients with schizophrenia, taking into account the psychopathology with respect to positive or negative symptoms.
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