Modeling Considerations for <i>In Vivo</i> Quantification of the Dopamine Transporter using [<sup>11</sup>C]PE2I and Positron Emission Tomography

DeLorenzo, Christine; Kumar, JS Dileep; Zanderigo, Francesca; Mann, J. John; Parsey, Ramin V.

doi:10.1038/jcbfm.2009.49

Cited by 34 publications

(39 citation statements)

References 38 publications

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“…Quantification of 123 I-PE2I binding to DAT is possible using kinetic or graphical analysis after bolus injection of the tracer and SPECT for 90 min or as a combination of bolus and constant infusion, for which unvarying levels in plasma and brain tissue are achieved after approximately 2 h (10,11). PE2I has also proven suitable as an 11 C-labeled PET probe (12). In 123 I-labeled form, neither PE2I nor FP-CIT gives rise to radiolabeled metabolites that can permeate the blood-brain barrier (13,14).…”

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confidence: 99%

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Ziebell

Holm-Hansen²,

Thomsen³

et al. 2010

J Nucl Med

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Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared the SPECT radioligands 123 I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ( 123 I-FP-CIT) and 123 I-N-(3-iodoprop-2E-enyl)-2-b-carbomethoxy-3b-(4-methylphenyl) ( 123 I-PE2I). 123 I-FP-CIT has a 10-fold higher selectivity than 123 I-FP-CIT for DAT versus SERT. Methods: Sixteen healthy individuals were scanned in random order with both radioligands. The radioligands were administered according to standard recommendations: 123 I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. 123 I-PE2I was administered in a bolus-infusion setup, and the nondisplaceable binding potential (BP ND ) was measured after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT was blocked by intravenous citalopram in 6 of the individuals. Results: The striatum-to-reference ratio 2 1 of 123 I-FP-CIT was on average 18% higher than the striatal BP ND of 123 I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for 123 I-FP-CIT than for 123 I-PE2I, both in target and in reference brain regions. Citalopram infusion led to significant reductions in both striatal (22.8% 6 20.4%, P , 0.05) and thalamic (63.0% 6 47.9%, P , 0.05) 123 I-FP-CIT binding ratios, whereas BP ND of 123 I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% 6 30.1%, P , 0.001) plasma 123 I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma 123 I-PE2I remained stable. Conclusion: 123 I-FP-CIT and 123 I-PE2I had approximately the same targetto-background ratios, but per injected megabecquerel, 123 I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that 123 I-FP-CIT, but not 123 I-PE2I, brain images have a highly interindividual but significant signal contribution from SERT. Whether the SERT signal contribution is of clinical importance needs to be established in future patient studies.

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Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Ziebell

Holm-Hansen²,

Thomsen³

et al. 2010

J Nucl Med

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“…Although 11 C-PE2I is a suitable DAT radioligand, there are potential limitations for robust in vivo quantification. First, because of the slow kinetics and late peak equilibrium, accurate quantification requires imaging for longer than 90 min (5). For patients with Parkinson disease, it could be difficult to lie still in the PET scanner for such a long time, and a tracer with faster kinetics could be more advantageous for wide clinical applications.…”

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confidence: 99%

“…Kinetic analysis with a 2-tissuecompartment model (2-TCM) and the parent input function is the reported quantification method for 11 C-PE2I (2,4,5). Therefore, this method (method 1) was applied to the quantification of 11 C-PE2I and 18 F-FE-PE2I.…”

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confidence: 99%

Kinetic Analysis and Quantification of the Dopamine Transporter in the Nonhuman Primate Brain with ¹¹C-PE2I and ¹⁸F-FE-PE2I

Varrone¹,

Tóth²,

Steiger³

et al. 2010

J Nucl Med

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nortropane ( 18 F-FE-PE2I) is a novel radioligand for dopamine transporter (DAT) PET. As compared with 11 C-N-(3-iodoprop-2E-enyl)-2b-carbomethoxy-3b-(4-methylphenyl)nortropane ( 11 C-PE2I), 18 F-FE-PE2I shows faster kinetics and more favorable metabolism, with less production of a radiometabolite with intermediate lipophilicity (M1), which-in the case of 11 C-PE2I-has been shown to enter the rat brain. In this study, we compared DAT quantification with 11 C-PE2I and 18 F-FE-PE2I in nonhuman primates, using kinetic and graphical analysis with the input function of both the parent and the radiometabolite, to assess the potential contribution of the radiometabolite. Methods: Three rhesus monkeys were examined with 11 C-PE2I and 18 F-FE-PE2I using the HRRT system. Arterial input functions of the parent and radiometabolite M1 were measured. Kinetic and graphical analyses were applied using either the parent input (methods 1 and 3) or the parent plus radiometabolite input (methods 2 and 4). Outcome measures were distribution volumes (V T and V ND ), specific-to-nondisplaceable tissue radioactivity ratio at equilibrium (BP ND ; parent input), and specific-to-nondisplaceable tissue radioactivity ratio at equilibrium in the presence of metabolites (R T ; parent plus radiometabolite input). Results: 11 C-PE2I showed higher distribution volumes than 18 F-FE-PE2I calculated with methods 1 and 3 (striatal V T , ;300%; V ND in cerebellum, ;30%). With methods 2 and 4, V T in the striatum was approximately 60% higher in the case of 11 C-PE2I, whereas no difference in V ND was found in the cerebellum. For each radioligand, BP ND estimated with methods 1 and 3 tended to be higher than R T estimated with methods 2 and 4. However, the bias of BP ND , compared with R T , was much larger for 11 C-PE2I (40%-60% in the caudate and putamen) than for 18 F-FE-PE2I (,10% in the caudate and putamen). Conclusion: The direct comparison between the radioligands confirmed that 18 F-FE-PE2I shows faster kinetics and more favorable metabolism than 11 C-PE2I. The kinetic and graphical analyses with the input function of the parent and radiometabolite showed that the bias in BP ND was much lower for 18 F-FE-PE2I than for 11 C-PE2I and suggested that the lower production of the radiometabolite M1 would make 18 F-FE-PE2I more suitable for the DAT quantification. Further studies in humans are necessary to confirm these findings.

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“…Four previously acquired test-retest datasets were considered: 12 scans with CUMI, 14 20 with DASB, 15 14 with PE2I, 16 and 10 with WAY. 17 The studies were performed in accordance with the Declaration of Helsinki and The Institutional Review Boards of Columbia University Medical Center and New York State Psychiatric Institute approved the protocol.…”

Section: Materials and Methods Subjectsmentioning

confidence: 99%

Model-Free Quantification of Dynamic PET Data Using Nonparametric Deconvolution

Zanderigo

Parsey

Ogden

2015

J Cereb Blood Flow Metab

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Dynamic positron emission tomography (PET) data are usually quantified using compartment models (CMs) or derived graphical approaches. Often, however, CMs either do not properly describe the tracer kinetics, or are not identifiable, leading to nonphysiologic estimates of the tracer binding. The PET data are modeled as the convolution of the metabolite-corrected input function and the tracer impulse response function (IRF) in the tissue. Using nonparametric deconvolution methods, it is possible to obtain model-free estimates of the IRF, from which functionals related to tracer volume of distribution and binding may be computed, but this approach has rarely been applied in PET. Here, we apply nonparametric deconvolution using singular value decomposition to simulated and test-retest clinical PET data with four reversible tracers well characterized by CMs (

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Modeling Considerations for In Vivo Quantification of the Dopamine Transporter using [¹¹C]PE2I and Positron Emission Tomography

Cited by 34 publications

References 38 publications

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Kinetic Analysis and Quantification of the Dopamine Transporter in the Nonhuman Primate Brain with ¹¹C-PE2I and ¹⁸F-FE-PE2I

Model-Free Quantification of Dynamic PET Data Using Nonparametric Deconvolution

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Modeling Considerations for In Vivo Quantification of the Dopamine Transporter using [11C]PE2I and Positron Emission Tomography

Cited by 34 publications

References 38 publications

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands 123I-FP-CIT and 123I-PE2I

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands 123I-FP-CIT and 123I-PE2I

Kinetic Analysis and Quantification of the Dopamine Transporter in the Nonhuman Primate Brain with 11C-PE2I and 18F-FE-PE2I

Model-Free Quantification of Dynamic PET Data Using Nonparametric Deconvolution

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Modeling Considerations for In Vivo Quantification of the Dopamine Transporter using [¹¹C]PE2I and Positron Emission Tomography

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands ¹²³I-FP-CIT and ¹²³I-PE2I

Kinetic Analysis and Quantification of the Dopamine Transporter in the Nonhuman Primate Brain with ¹¹C-PE2I and ¹⁸F-FE-PE2I