18F-DOPA PET Research Articles

La TEP dans les tumeurs malignes cérébrales

Normal biodistribution of FDG includes intense physiologic uptake in the brain, which consumes glucose. The high background therefore makes it difficult to detect the foci taking up glucose, which correspond to malignant lesions. FDG PET is nevertheless clinically useful for detecting high-grade gliomas, cerebral lymphomas and, in some cases, unexpected brain metastases in whole-body PET examinations. As an adjunct to CT and MRI, FDG-PET can make stereotactic radiosurgery more precise in targeting primary or secondary brain cancers and can differentiate necrotic fibrosis from viable cancer tissue during follow-up in cases of abnormal or equivocal MRI results. When available, methionine-(11C) PET delineates low grade gliomas accurately. Several fluorine (18F)-labeled radiopharmaceuticals have been proposed in this setting, with FET and FDOPA apparently the most effective. Four original clinical cases illustrating performances of FET and FDOPA PET in this setting are presented.

La TEP dans le cancer de la glande thyroïde

FDG PET can detect thyroid cancer in patients referred for exploration of a different cancer. Because of its lack of specificity, however, this modality is not indicated for examination of thyroid nodules: ultrasonography and fine needle biopsy with cytology allow histological diagnosis, which can be completed by iodine-123 scintigraphy when an autonomous nodule is suspected. No information is currently available about the utility of FDG PET in preoperative staging. In follow-up of patients undergoing thyroidectomy for adenocarcinoma, FDG PET is useful for detecting recurrence in cases where serum thyroglobulin levels rise and iodine-131 scintigraphy is negative: surgical resection may be appropriate. Nonetheless FDG PET should be performed more widely and earlier: the initial presence of foci positive for FDG is a major predictor of shorter survival, and most cancer lesions take up either iodine or FDG. In follow-up of medullary carcinoma, FDG PET detects residual tissue better than any other scintigraphic procedures, especially when serum levels of CEA (carcinoembryonic antigen) are rising rapidly. FDOPA PET seems to have better sensitivity than FDG-PET and may be useful in occult recurrence, as three case reports indicate.

Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study

To assess individual treatment options for patients with carcinoid tumours, accurate knowledge of tumour localisation is essential. We aimed to test the diagnostic sensitivity of 6-[fluoride-18]fluoro-levodopa ((18)F-DOPA PET), compared with conventional imaging methods, in patients with carcinoid tumours. In a prospective, single-centre, diagnostic accuracy study, (18)F-DOPA PET with carbidopa pretreatment was compared with somatostatin-receptor scintigraphy (SRS), CT, and combined SRS and CT in 53 patients with a metastatic carcinoid tumour. The performance of all imaging methods was analysed for individual patients, for eight body regions, and for the detection of individual lesions. PET and CT images were fused to improve localisation. To produce a composite reference standard, we used cytological and histological findings; all imaging tests, including secondary assessments for newly found lesions; follow-up; and biochemical data. Sensitivities were calculated and compared. In patient-based analysis, we recorded sensitivities of 100% (95% CI 93-100) for (18)F-DOPA-PET, 92% (82-98) for SRS, 87% (75-95) for CT, and 96% (87-100) for combined SRS and CT (p=0.45 for (18)F-DOPA PET vs combined SRS and CT). However, (18)F-DOPA PET detected more lesions, more positive regions, and more lesions per region than combined SRS and CT. In region-based analysis, sensitivity of (18)F-DOPA PET was 95% (90-98) versus 66% (57-74) for SRS, 57% (48-66) for CT, and 79% (70-86) for combined SRS and CT (p=0.0001, PET vs combined SRS and CT). In individual-lesion analysis, corresponding sensitivities were 96% (95-98), 46% (43-50), 54% (51-58), and 65% (62-69; p<0.0001 for PET vs combined SRS and CT). If the improved tumour localisation seen with (18)F-DOPA-PET compared with conventional imaging is confirmed in future studies, this imaging method could replace use of SRS, help improve prediction of prognosis, and be used to assess patients' response to treatment for carcinoid tumours.

Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study

We analyzed (18)F-dopa PET data from 11 members of kindreds with familial progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic dysfunction. Three clinically-affected PSP patients showed reduced (18)F-dopa uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic subject exhibited progressive putamen dopaminergic dysfunction. 60% of subjects with abnormal (18)F-dopa scans developed PSP subsequently. This is the first in vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal (18)F-dopa uptake in susceptible relatives may predict later clinical disease.

The SCA17 phenotype can include features of MSA-C, PSP and cognitive impairment

Spinocerebellar ataxia (SCA) 17 is a dominant neurodegenerative disorder characterized by ataxia, cognitive decline, dystonia, and parkinsonism. The disease is caused by unstable cytosine–adenine–guanine (CAG) trinucleotide expansion mutation coding for polyglutamine tracts in the TATA box-binding protein (TBP), a general transcription initiation factor. Herein, we report a SCA17 case with a phenotype not previously reported, which consisted of progressive ataxia, autonomic dysfunction, parkinsonism, supranuclear palsy and cognitive impairment. Cerebrospinal fluid study and 18F-dopa PET scanning demonstrated dopamine deficiency and nigrostrital degeneration. This case expands the current phenotype associated with SCA17. SCA17 should be considered in the differential diagnosis of cases resembling multiple system atrophy, especially those with atypical features.

Localization of residual disease in medullary thyroid carcinoma by integrated 18F-DOPA PET / CT

Localization of residual disease in medullary thyroid carcinoma by integrated 18F-DOPA PET / CT

18F]FDOPA PET and Clinical Features in Parkinsonism Due to Manganism

18F]FDOPA PET and Clinical Features in Parkinsonism Due to Manganism

Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation

We read with interest the article by Khan et al.1 The authors studied asymptomatic parkin heterozygotes by 18F-dopa PET and found a significant reduction of uptake in putamen, caudate, dorsal and ventral midbrain. An interesting observation relates to the subtle extrapyramidal symptoms in four of these “asymptomatic” carriers. The authors recommended follow-up to verify whether they develop parkin disease. One of our patients with a single parkin mutation developed parkin disease 23 years after the manifestation of tremor …

PET imaging of disease progression in Parkinson's disease with deep brain stimulation of the subthalamic nucleus

Recently, neurosurgical interventions experienced a renaissance in the treatment of motor complications in advanced PD. In particular, deep brain stimulation of the subthalamic nucleus (STN-DBS) has become a highly effective neurosurgical treatment option. Hyper-active STN neurons occuring as a result of striatal dopamine depletion in PD exert a strong glutamatergic outflow on their projection sites, such as the dopaminergic neurons of the substantia nigra. Therefore, some authors proposed neuroprotective properties of STN over-activity blockade by the DBS technique. In order to investigate this hypothesis, our groups performed a prospective serial 18-Fluorodopa (FDOPA) PET study which determinated disease progression during the first years after STN-DBS implantation in 30 patients with advanced PD patients. FDOPA PET has been proven as a reliable measure of PD progression. Dependent on the PET data analysis approach, annual progression rates relative to baseline were 9.5 to 12.4% in the caudate and 10.7 to 12.9% in the putamen. This is the first functional imaging study demonstrating a continuous decline of dopaminergic function in advanced PD patients under clinically effective bilateral STN stimulation. The progression rates in patients with STN-DBS are within the range of previously reported data from longitudinal imaging studies in PD. Therefore, neuroprotective properties of DBS in the STN target could not be confirmed.

Comparison of FP-CIT SPECT with F-DOPA PET in patients with de novo and advanced Parkinson’s disease

Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system. Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage). Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r = 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r = 0.84, both p < 0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (rho = -0.52 for both techniques), UPDRS-III (rho = -0.38 for F-DOPA; rho = -0.45 for FP-CIT) and disease duration (rho = -0.59 for F-DOPA; rho = -0.49 for FP-CIT, all p < 0.05). FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.

Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson’s disease

Objectives: The aetiology of the cognitive changes seen in Parkinson’s disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This...

A comparative F-dopa and FDG PET study of parkinsonian subjects without evidence of dopaminergic dysfunction

A comparative F-dopa and FDG PET study of parkinsonian subjects without evidence of dopaminergic dysfunction

F-18 FDG and F-18 FDOPA PET Brain Imaging in Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis (SSPE), originally described by Dawson in 1933, is today recognized as a progressive neurodegenerative disease caused by latent infection with mutated measles virus. Its threat is higher in underdeveloped nations and is expected to increase in the United States because of the measles epidemic in 1988-1990. Concomitant F-18 FDG PET and F-18 FDOPA PET brain images in SSPE appear to be unusual.

18F-DOPA PET superior for staging of neuroendocrine tumors

4085 Background: The aim of the study was to assess the value of whole body 18-fluoro-L-DOPA positron emission tomography (F-DOPA PET) for staging and restaging of patients with neuroendocrine tumo...

Striatal dopamine during sensorial stimulations: A [ 18F]FDOPA PET study in human and cats

Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsilateral striatum and to decrease it in the homologous contralateral structure. Using positron emission tomography in both humans and cats, the present study shows that such sensory stimulations greatly reduce [ 18F]FDOPA accumulation ipsilateral to the stimulation (by 40.4% and 26.4% in the human caudate and putamen, respectively, and by 33.3% in the cat striatum). This decrease in striatal [ 18F]FDOPA uptake suggests a reduced DA storage resulting from the increased amine release. No change was observed in the contralateral striatum in neither human or cat suggesting, in contrast, that [ 18F]FDOPA accumulation is not facilitated by decreased DA release. These results support the hypothesis that sensory stimulations activate a non-synaptic mode of dopamine release.

Early-onset Parkinson's disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study

Early Onset Parkinson's Disease (EOPD) is characterized by selective degeneration of nigrostriatal dopaminergic neurons and a marked response to levodopa. However, at present, few methods are available as diagnostic tools for EOPD except for 18F-DOPA PET. In addition, little is known about the correlation between clinical severity, neuroimaging grading and genetic susceptibility. In the present study, 99mTc-TRODAT-1 SPECT and brain MRI were used to identify 30 cases of non-familial EOPD from a Chinese cohort of 230. All 30 PD patients had an age of onset of less than 55 years (mean age at onset, 41.5±9.3 years). Each of the 30 EOPD cases was sub-classified into one of five stages based on the 99mTc-TRODAT-1 SPECT findings. In the early stages of PD (stages 1 and 2), a lower uptake of 99mTc-TRODAT-1 in the putamen was found, while uptake in the caudate nucleus was normal. In the latter stages (stages 3, 4, 5), 24 patients revealed a diffuse and uniform loss of 99mTc-TRODAT-1 uptake in the putamen and the caudate nucleus. Further, in conventional genetic studies of the 30 patients, six novel mutations were found in the Parkin gene, and these included five heterozygous point mutations (C441R, Q311H, V258M, C212G, and S193I) and one homozygous deletion (exon 10-12). Known polymorphisms (Ser167Asn, Val380Leu) were also found in a number of patients. However, gene dosage analysis did not reveal any compound heterozygous mutations in these 30 patients using quantitative duplex PCR. This is the first study to examine EOPD patients of Chinese ethnic background (not exhibiting a definite familial trait), to offer a complete genetic analysis of the Parkin gene, and to correlate clinical stages of the disease with dopamine re-uptake.

18F]FDOPA PET and clinical features in parkinsonism due to manganism

Manganese exposure reportedly causes a clinically and pathophysiologically distinct syndrome from idiopathic Parkinson's disease (PD). We describe the clinical features and results of positron emission tomography with 6-[18F]fluorodopa ([18F]FDOPA PET) of a patient with parkinsonism occurring in the setting of elevated blood manganese. The patient developed parkinsonism associated with elevated serum manganese from hepatic dysfunction. [18F]FDOPA PET demonstrated relatively symmetric and severely reduced [18F]FDOPA levels in the posterior putamen compared to controls. The globus pallidum interna had increased signal on T1-weighted magnetic resonance imaging (MRI) images. We conclude that elevated manganese exposure may be associated with reduced striatal [18F]FDOPA uptake, and MRI may reveal selective abnormality within the internal segment of the pallidum. This case suggests that the clinical and pathophysiological features of manganese-associated parkinsonism may overlap with that of PD.

Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation

Parkin disease is usually autosomal recessive; however, two studies have shown that asymptomatic heterozygotes have nigrostriatal dysfunction and even manifest subtle extrapyramidal signs. The authors used 18F-dopa PET to study 13 asymptomatic parkin heterozygotes and found a significant reduction of (18)F-dopa uptake in caudate, putamen, ventral, and dorsal midbrain compared with control subjects. Four had subtle extrapyramidal signs. Parkin heterozygosity is a risk factor for nigrostriatal dysfunction and in some may contribute to late-onset Parkinson disease.

Visualization of the Gall Bladder on F-18 FDOPA PET Imaging: A Potential Pitfall

Abstract: The ability to label dihydroxyphenylalanine (DOPA) with the positron-emitting isotope F-18 has helped to identify the deficiency of dopamine synthesis and storage within presynaptic striatal nerve terminals. FDOPA PET, therefore, has been used in the diagnosis of early Parkinson disease and the differentiation of a parkinsonian syndrome from other movement disorders. Furthermore, the uptake and metabolism of amino acids by tumors makes F-18 FDOPA PET a suitable alternative to F-18 FDG PET imaging, although the experience in this situation is very limited. Because the main indication for FDOPA PET imaging in the past has been the brain in suspected Parkinson disease, there is a paucity of information on normal whole-body distribution of FDOPA. The author reports a case in which intense uptake of the tracer in the gall bladder mimicked a large liver metastasis from a neuroendocrine primary, but correlative CT and knowledge of the normal biliary route of excretion of the radiopharmaceutical helped to avoid a diagnostic pitfall.

PET neuroimaging and mutations in the DJ-1 gene

Mutations in the DJ-1 gene lead to autosomal recessive early-onset parkinsonism. We performed F-DOPA and FDG PET neuroimaging in two parkinsonism patients homozygous for DJ-1 mutations, three relatives heterozygous for a DJ-1 mutation and one non-carrier, all from the originally described kindred from The Netherlands. Their characteristics were compared to those of typical Parkinson's disease patients and healthy controls. Both parkinsonism patients had reduced F-DOPA uptake concordant with typical Parkinson's disease. In the, clinically unaffected, heterozygous relatives, F-DOPA metabolism was unremarkable, thus not suggesting a dosage effect of the DJ-1 gene.