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. 2021 Jun 3;30(2):69-78.
doi: 10.4274/mirt.galenos.2021.08831.

Pharmacokinetic Modeling of 18F-FDOPA PET in the Human Brain for Early Parkinson's Disease

Wirunpatch Buratachwatanasiri  1   2 , Maythinee Chantadisai  3 , Jaruwan Onwanna  2   4 , Yuda Chongpison  5 , Yothin Rakvongthai  1   2   3 , Kitiwat Khamwan  1   2   3
Affiliations

Pharmacokinetic Modeling of 18F-FDOPA PET in the Human Brain for Early Parkinson's Disease

Wirunpatch Buratachwatanasiri et al. Mol Imaging Radionucl Ther. .

Abstract
in English, Turkish

Objectives: Early detection is essential for the treatment approaches of Parkinson's disease (PD). Clinical criteria alone may be insufficient to distinguish early PD from other conditions. This study aimed to investigate the transfer rate constants of 6-18F-fluoro-L-dopa (18F-FDOPA) in positron emission tomography (PET) brain images as a sensitive parameter to detect early PD.

Methods: Retrospective 18F-FDOPA PET data of five patients with early PD were collected. PET data were acquired for 90 min after intravenous injection of 306-379 MBq 18F-FDOPA, and reconstructed into a series of 18 five-minute frames. Reoriented PET images were coregistered and normalized with the PET brain template on the statistical parametric mapping. The 18F-FDOPA activity concentrations were measured in the striatum, caudate, and putamen on both sides: Contralateral (as PD) and ipsilateral (as control) to the main motor symptoms. The pharmacokinetic model was generated using the SAAM II simulation software. The transfer rate constants across the blood-brain barrier (forward, K1 and reverse, k2) and decarboxylation rate constants (k3) were estimated in these regions.

Results: The activity uptakes in the contralateral striatum (0.0323%±0.0091%) and putamen (0.0169%±0.0054%) were significantly lower than the control (0.0353%±0.0086%, 0.0199%±0.0054%, respectively). The K1 and k3 were significantly lower in the contralateral striatum and putamen (p<0.05). There were no significant differences in any transfer rate constants in the caudate.

Conclusion: The transfer rate constants (K1 and k3) of 18F-FDOPA on the contralateral striatum and putamen were significantly lower than the control. These biokinetic data could be potential indicators for quantitative detection of early PD diagnosis.

Amaç: Parkinson hastalığının (PH) tedavi yaklaşımında erken tanı önemlidir. Klinik kriterler tek başına erken PH’yi diğer nedenlerden ayırt etmek için yetersiz olabilir. Bu çalışmada, 6-18F-floro-L-dopa (18F-FDOPA) pozitron emisyon tomografisi (PET) beyin görüntülemede transfer hızı sabitlerinin erken PH saptanmasında duyarlı bir parametre olup olmadığının araştırılması amaçlanmıştır.

Yöntem: Erken PH’li beş hastanın geriye dönük 18F-FDOPA PET verileri toplandı. PET verileri, 306-379 MBq 18F-FDOPA’nın intravenöz enjeksiyonundan sonra 90 dakika süreyle alındı ve 18 adet beşer dakikalık bir dizi halinde rekonstrükte edildi. Reoryante edilen PET görüntüleri istatistiksel parametrik haritalama üzerindeki beyin PET şablonu ile birleştirildi ve normalize edildi. 18F-FDOPA aktivite konsantrasyonları her iki tarafta striatum, kaudat ve putamende ölçüldü: Ana motor semptomlara karşı kontralateral (PH olarak) ve ipsilateral (kontrol olarak). Farmakokinetik model SAAM II simülasyon yazılımı kullanılarak geliştirildi. Bu bölgelerde kan-beyin bariyeri boyunca transfer hızı sabitleri (ileri, K1 ve geri, k2) ve dekarboksilasyon hızı sabitleri (k3) tahmini ölçümleri yapıldı.

Bulgular: Kontralateral striatumda (%0,0323±%0,0091) ve putamende (%0,0169±%0,0054) aktivite alımları kontrolden anlamlı derecede düşüktü (sırasıyla; 0,0353%±0,0086%, 0,0199%±0,0054%). K1 ve k3 kontralateral striatum ve putamenlerde anlamlı derecede düşüktü (p<0,05). Kaudattaki herhangi bir transfer hızı sabitinde anlamlı bir fark yoktu.

Sonuç: Kontralateral striatum ve putamendeki 18F-FDOPA’nın transfer hızı sabitleri (K1 ve k3) kontrolden anlamlı derecede düşüktü. Bu biyokinetik veriler, erken evre PH tanısının kantitatif tespiti için potansiyel göstergeler olabilir.

Keywords: 18F-FDOPA; early Parkinson’s disease detection; pharmacokinetic model; quantitative analysis; statistical parametric mapping.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Schematic flowchart showing the semi-automated segmentation in the striatum, caudate, and putamen regions using the statistical parametric mapping (SPM) MRI: Magnetic resonance imaging, 18F-FDOPA: 18F-fluoro-L-dopa, PET: Positron emission tomography, ICBM: International Consortium for Brain Mapping
Figure 2
Figure 2
(Left) region of interest over right side of the striatum, and (right) the histogram output
Figure 3
Figure 3
Two-tissue-compartment and three-rate constant for describing the FDOPA kinetics in early PD patients following Wahl and Nahmias (22) FDOPA: Fluoro-L-dopa, PD: Parkinson’s disease, FDA: Fluorodopamine
Figure 4
Figure 4
Mean (± 1 SD) time-activity curves in the (A) striatum, (B) caudate, and (C) putamen. Blue and red round markers represent patient’s data obtained from the contralateral and ipsilateral side, respectively. Green and yellow lines represent the model fitted from the contralateral and ipsilateral side, respectively SD: Standard deviation
Figure 5
Figure 5
Box plots of the transfer rate constants in the contralateral (red) and ipsilateral (blue). (A) striatum and (B) putamen
Figure 6
Figure 6
Example of static 18F-FDOPA PET images in a case of the early PD with HY rate stage II. The arrows indicate the relatively mild decreased FDOPA uptake demonstrated by the red light shading at the dorsal part of left posterior putamen 18F-FDOPA: 18F-fluoro-L-dopa, PET: Positron emission tomography, PD: Parkinson’s disease, HY: Hoehn and Yahr
See this image and copyright information in PMC

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