Combined Striatal Binding and Cerebral Influx Analysis of Dynamic <sup>11</sup>C-Raclopride PET Improves Early Differentiation Between Multiple-System Atrophy and Parkinson Disease

Laere, Koen Van; Clerinx, Kristien; Dhondt, Elisabeth; Groot, Tjibbe de; Vandenberghe, Wim

doi:10.2967/jnumed.109.070144

Cited by 41 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 The radionuclides most commonly used for PET are 18 F and 11 C, which are produced using an accelerator. [21][22][23] Other metallic positron emitters, such as, 86 Y, 64 Cu, and 68 Ga also can be used for PET, [24][25][26][27][28][29][30] and of these, 68 Ga is the most promising, because it can be obtained using a commercially available generator system consisting of an inorganic matrix immobilizing the parent radionuclide 68 Ge. 31 This availability has led to great interest in the development of 68 Ga-labeled agents, because of its cost and convenience benefits.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Hoigebazar

Jeong

Hong

et al. 2011

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Hoigebazar

Jeong

Hong

et al. 2011

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

“…However, as demonstrated for other ligands (19,20), pharmacokinetic analyses of 11 C-PIB studies may yield diagnostically valuable estimates of relative regional CBF: Invasive compartment models used for 11 C-PIB quantification (21,22) provided estimates of K 1 (i.e., the rate constant for ligand transfer from arterial plasma to tissue). In radiotracers with a high permeability-surface product and, consequently, a high level of first-pass extraction, K 1 is closely related to CBF.…”

mentioning

confidence: 98%

Dual-Biomarker Imaging of Regional Cerebral Amyloid Load and Neuronal Activity in Dementia with PET and ¹¹C-Labeled Pittsburgh Compound B

et al. 2011

View full text Add to dashboard Cite

PET studies with biomarkers of regional neuronal activity (cerebral glucose metabolism or blood flow [CBF]) and amyloid-b (Ab) depositions provide complementary information for the early diagnosis of dementia and follow-up of patients with dementia. We investigated the validity of relative regional CBF estimates (R 1 ) gained from pharmacokinetic analyses of 11 Clabeled Pittsburgh compound B ( 11 C-PIB) PET studies as a marker of neuronal activity and neurodegeneration. Methods: Twenty-two patients with cognitive impairment (16 patients with early Alzheimer disease) underwent 18 F-FDG and 11 C-PIB PET studies for the assessment of regional glucose metabolism and Ab load. Parametric images of R 1 (relative CBF) and binding potential (BP ND ; Ab load) were generated by 2-step simplified reference tissue model (SRTM2) analyses of dynamic 11 C-PIB data. Volume-of-interest and voxel-based statistical analyses were performed to investigate the association between normalized 18 F-FDG uptake and 11 C-PIB R 1 and the correlation of these measures with symptom severity (Mini-Mental State Examination [MMSE] scores) in patients with Alzheimer disease. Results: SRTM2 analyses provided high-quality 11 C-PIB R 1 images that were comparable to 18 F-FDG PET images. Regional 11 C-PIB R 1 values strongly correlated with normalized regional 18 F-FDG uptake when correlations were calculated separately for each patient (R 2 [mean 6 SD], 0.73 6 0.11) or across all regions of all patients (R 2 , 0.62). A regression model including 18 F-FDG uptake, subject identification, and region grouping (into cortical, subcortical, and limbic regions to allow for possible differences in flow/metabolism coupling) accounted for 86% of total 11 C-PIB R 1 variability. Voxel-based correlation analyses of 18 F-FDG uptake and 11 C-PIB R 1 with MMSE scores revealed similar core findings of positive correlations in the posterior cingulate gyrus/precuneus and negative correlations (preserved activity) in the bilateral sensorimotor cortex. There was no correlation between Ab load (BP ND ) and MMSE scores. Conclusion: These results strongly suggest that 11 C-PIB R 1 can serve as a complementary biomarker of neuronal activity and, thus, neurodegeneration in addition to Ab load given by 11 C-PIB BP ND . Further studies are needed to validate the diagnostic value of dual-biomarker 11 C-PIB PET studies in comparison with combined 18 F-FDG and 11 C-PIB PET studies. Compared with the latter, dual-biomarker 11 C-PIB PET greatly reduces costs and burden for patients.

show abstract

“…Once a workflow is established, kinetic analyses can be accomplished by a trained user within 10-15 min. Finally, though not addressed in the present study, kinetic analyses such as SRTM2 and MRTM2 also provide an estimate of relative ligand delivery (R 1 ) that is proportional to relative cerebral blood flow and may thus serve as a diagnostically useful marker of regional neuronal activity and neurodegeneration (23,24).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Striatal Dopamine D2/D3 Receptor Availability with PET and ¹⁸F-Desmethoxyfallypride: Comparison of Imaging Protocols Suited for Clinical Routine

et al. 2012

View full text Add to dashboard Cite

Assessment of striatal dopamine receptor availability with 18 F-desmethoxyfallypride PET is of high diagnostic utility in parkinsonism. The present study was undertaken to define the optimal clinical scan protocol with regard to quantification accuracy and scan time. Methods: Fourteen patients with parkinsonian syndromes underwent 18 F-desmethoxyfallypride PET over 90 min. Volume-of-interest analyses were performed after spatial normalization, with the right and left caudate nuclei and putamina as target regions and the cerebellum as reference region. The estimate of target region binding potential (relative to nondisplaceable radioligand in tissue) (BP ND ) provided by the 2-step simplified reference tissue model (SRTM2) served as the reference standard. Additional analyses included the multilinear reference tissue model 2 (MRTM2), noninvasive graphical analyses, and single-scan analyses (peak-equilibrium analysis at 35-65 min [PEA]; pseudoequilibrium analysis at 60-90 min [PsEA]). Results: SRTM2 and MRTM2 yielded virtually identical results (mean BP ND difference 5 0.1% 6 0.5%, r 2 5 1.0). Noninvasive graphical analyses with and without inclusion of the k 2 9 term were affected by a small BP ND bias (2.5% 6 3.6% and 25.0% 6 6.7%, respectively), although correlations with SRTM2 were still excellent (r 2 5 1.0 and 0.98, respectively). In turn, singlescan analyses suffered from limited precision (PEA, mean BP ND bias 5 0.7% 6 13.0%, r 2 5 0.90) or a considerable positive bias (PsEA, 19.2% 6 7.1%, r 2 5 0.98). Shortening scan time to 70 and 60 min resulted in an acceptable average BP ND change (,5% decline) for SRTM2/MRTM2 and graphical analysis with inclusion of the k 2 9 term, respectively. Conclusion: Kinetic reference tissue model analyses of 18 F-desmethoxyfallypride PET data offer the least biased results at a well-tolerable scan duration and should thus be pursued whenever possible. Single-scan analyses may be pragmatic alternatives that, however, suffer from a relevant positive bias (PsEA) or limited precision (PEA).

show abstract

Combined Striatal Binding and Cerebral Influx Analysis of Dynamic ¹¹C-Raclopride PET Improves Early Differentiation Between Multiple-System Atrophy and Parkinson Disease

Cited by 41 publications

References 30 publications

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Dual-Biomarker Imaging of Regional Cerebral Amyloid Load and Neuronal Activity in Dementia with PET and ¹¹C-Labeled Pittsburgh Compound B

Assessment of Striatal Dopamine D2/D3 Receptor Availability with PET and ¹⁸F-Desmethoxyfallypride: Comparison of Imaging Protocols Suited for Clinical Routine

Contact Info

Product

Resources

About

Combined Striatal Binding and Cerebral Influx Analysis of Dynamic 11C-Raclopride PET Improves Early Differentiation Between Multiple-System Atrophy and Parkinson Disease

Cited by 41 publications

References 30 publications

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

Dual-Biomarker Imaging of Regional Cerebral Amyloid Load and Neuronal Activity in Dementia with PET and 11C-Labeled Pittsburgh Compound B

Assessment of Striatal Dopamine D2/D3 Receptor Availability with PET and 18F-Desmethoxyfallypride: Comparison of Imaging Protocols Suited for Clinical Routine

Contact Info

Product

Resources

About

Combined Striatal Binding and Cerebral Influx Analysis of Dynamic ¹¹C-Raclopride PET Improves Early Differentiation Between Multiple-System Atrophy and Parkinson Disease

Dual-Biomarker Imaging of Regional Cerebral Amyloid Load and Neuronal Activity in Dementia with PET and ¹¹C-Labeled Pittsburgh Compound B

Assessment of Striatal Dopamine D2/D3 Receptor Availability with PET and ¹⁸F-Desmethoxyfallypride: Comparison of Imaging Protocols Suited for Clinical Routine