6-[<sup>18</sup>F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

Hoshi, Hiroaki; Kuwabara, Hiroto; Léger, Gabriel C.; Cumming, Paul; Guttman, Mark; Gjedde, Albert

doi:10.1038/jcbfm.1993.8

Cited by 103 publications

(65 citation statements)

References 38 publications

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“…The occipital cortex (OCC) contains scant dopaminergic innervation; one can quantify striatal DA deficiency from the PUT:OCC ratio of 6-[ 18 F]fluorodopa-derived radioactivity [2,3]. Spatial resolution of conventional PET scanning is inadequate to visualize the substantia nigra (SN) in individuals.…”

Section: Abstract or Phrasesmentioning

confidence: 99%

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Goldstein¹,

Holmes²,

Bentho³

et al. 2008

Parkinsonism & Related Disorders

146

115

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Objective-Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).Methods-In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2 hours after 6-[ 18 F]fluorodopa injection, septal myocardial radioactivity measured 8 minutes after 6-[ 18 F] fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities.Results-PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[ 18 F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p<0.0001, p<0.0001, p=0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p<0.0001 each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001). Myocardial 6-[ 18 F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension (NOH)). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity).Conclusions-PD and MSA feature low PUT:OCC ratios of 6-[ 18 F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:OCC ratios of Corresponding author: David S. Goldstein, MD PhD, Clinical Neurocardiology Section, NINDS, NIH, 10 Center Drive MSC-1620, Building 10 Room 6N252, Bethesda, MD 20892-1620 USA, Phone: 301-496-2103, Fax: 301-402-0180, Blackberry: 301-675-1110 goldsteind@ninds.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Loss of sense of smell in PD has been associated with neuroimaging evidence of both central DA deficiency [22] and cardiac noradrenergic denervation [23]. Decreased olfaction also can occur in MSA [24,25], and it has been unclear how efficiently olfactory testing separates PD from MSA. NIH Public AccessThe main purpose of this study was to identify biomarkers that detect central DA deficiency and distinguish PD from MSA. Because of the impo...

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Section: Abstract or Phrasesmentioning

confidence: 99%

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Goldstein¹,

Holmes²,

Bentho³

et al. 2008

Parkinsonism & Related Disorders

146

115

View full text Add to dashboard Cite

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“…The striatal-to-occipital ratio (SOR) and the influx constant calculated with a graphical tissue reference approach (K i ref ) are commonly used as quantitative parameters in 18 F-FDOPA PET studies. They have been measured noninvasively in the dynamic mode with region-of-interest (ROI)-based approaches (9)(10)(11)(12). Both SOR and K i have been used to quantify regional dopamine metabolism and to reflect disease severity in PD (5,(13)(14)(15)(16).…”

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confidence: 99%

Simple Ratio Analysis of ¹⁸F-Fluorodopa Uptake in Striatal Subregions Separates Patients with Early Parkinson Disease from Healthy Controls

Jokinen¹,

Helenius²,

Rauhala³

et al. 2009

J Nucl Med

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6-18 F-fluoro-L-dopa ( 18 F-FDOPA) is widely used to investigate dopaminergic hypofunction, for instance, in Parkinson disease (PD). Conventionally, a 90-min scan with either a graphical or a metabolite-purified plasma input approach has been used for quantification. In the clinical setting, to increase compliance, especially in patients with more advanced disease, and to increase the efficacy of tracer and scanner time use, a shorter acquisition and a simple quantitative analysis are desirable. Taking into account the asymmetry of clinical symptoms and the uneven distribution of striatal dopaminergic hypofunction may also improve the use of 18 F-FDOPA PET in early disease detection. Therefore, we compared subregional striatal 18 F-FDOPA PET data from a large group of nonmedicated patients with early PD and a set of healthy elderly volunteers to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. Methods: A total of 89 nonmedicated patients with early PD and 21 healthy volunteers were studied with 18 F-FDOPA PET, and both a region-to-reference (striatal-to-occipital) ratio (SOR) calculated from 75 to 90 min after injection and a graphical analysis of data calculated from 15 to 90 min after 18 F-FDOPA injection (yielding the influx constant [K i ref ]) were used. Results: Both SOR and K i ref values in the PD patients were lowest, relative to those in the healthy controls, in the posterior putamen contralateral to the side with predominant clinical symptoms. The contralateral posterior putamen showed the largest areas under the receiver operating characteristic (ROC) curve-0.994 for SOR and 0.998 for K i ref -indicating excellent separation of the PD and control groups. The caudate nucleus and the ventral striatum were less impressive in this respect. Conclusion: A single 15-min scan 75 min after tracer injection seems to be sufficient for separating patients with PD from healthy controls in a clinical research environment. This method represents a powerful and economical alternative for research on the disease mechanism and differential diagnosis.

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“…In addition, K occ has been proven by many investigators to provide a sensitive discrimination between brain uptake in healthy volunteers and patients with PD. Several studies have compared the disease-discriminating ability of K i and K occ (Vingerhoets et al, 1994(Vingerhoets et al, , 1996Morrish et al, 1998;Takikawa et al, 1994;Leenders et al, 1990;Hoshi et al, 1993), with K occ usually found to be the better discriminator. The conventional interpretation of K i and K occ is as markers of DA synthesis and storage.…”

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confidence: 99%

Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[¹⁸F]Fluoro-dopa on the Relation between the ¹⁸F-Fluorodopa Tissue Input Uptake Rate Constant K_occ and the [¹⁸F]Fluorodopa Plasma Input Uptake Rate Constant K_i

Sossi

Holden

Fuente‐Fernández

et al. 2003

J Cereb Blood Flow Metab

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Summary:Parkinson disease is characterized by the loss of dopaminergic neurons, thus decreasing the system's ability to produce and store dopamine (DA). Such ability is often investigated using 18 F-fluorodopa (FD) positron emission tomography. A commonly used model to investigate the DA synthesis and storage rate is the modified Patlak graphical approach. This approach allows for both plasma and tissue input functions, yielding the respective uptake rate constants K i and K occ . This method requires the presence of an irreversible compartment and the absence of any nontrapped tracer metabolite. In the case of K occ , this last assumption is violated by the presence of the FD metabolite 3-O-methyl-[18 F]fluoro-dopa (3OMFD), which makes the K occ evaluation susceptible to a downward bias. It was found that both K i and K occ are influenced by DA loss and thus are not pure measures of DA synthesis and storage. In the case of K occ , the presence of 3OMFD exacerbates the effect of DA egress, thus introducing a disease-dependent bias in the K occ determination. These findings imply that K i and K occ provide different assessments of disease severity and that, as disease progresses, K i and especially K occ become more related to DA storage capacity and less to the DA synthesis rate.

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6-[¹⁸F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

Cited by 103 publications

References 38 publications

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Simple Ratio Analysis of ¹⁸F-Fluorodopa Uptake in Striatal Subregions Separates Patients with Early Parkinson Disease from Healthy Controls

Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[¹⁸F]Fluoro-dopa on the Relation between the ¹⁸F-Fluorodopa Tissue Input Uptake Rate Constant K_occ and the [¹⁸F]Fluorodopa Plasma Input Uptake Rate Constant K_i

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6-[18F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

Cited by 103 publications

References 38 publications

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy

Simple Ratio Analysis of 18F-Fluorodopa Uptake in Striatal Subregions Separates Patients with Early Parkinson Disease from Healthy Controls

Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[18F]Fluoro-dopa on the Relation between the 18F-Fluorodopa Tissue Input Uptake Rate Constant Kocc and the [18F]Fluorodopa Plasma Input Uptake Rate Constant Ki

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6-[¹⁸F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

Simple Ratio Analysis of ¹⁸F-Fluorodopa Uptake in Striatal Subregions Separates Patients with Early Parkinson Disease from Healthy Controls

Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[¹⁸F]Fluoro-dopa on the Relation between the ¹⁸F-Fluorodopa Tissue Input Uptake Rate Constant K_occ and the [¹⁸F]Fluorodopa Plasma Input Uptake Rate Constant K_i