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Quantification of Dopamine Transporter by ¹²³I-PE2I SPECT and the Noninvasive Logan Graphical Method in Parkinson’s Disease

¹ Nuclear Medicine Department, Institut National de la Santé et de la Recherche Médicale Unit 316, Bretonneau Hospital, Tours, France
² Nuclear Medicine Department Équipe d’Accueil 3033, Purpan Hospital, Toulouse, France
³ Clinical Research Center, François Rabelais University, Tours, France
⁴ Basal Gang, Laboratoire de Neurophysiologie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5543, Victor Segalen University, Bordeaux, France

(E)-N-(3-iodoprop-2-enyl)-2ß-carbomethoxy-3ß-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with ¹²³I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed ¹²³I-PE2I SPECT on healthy volunteers and patients with Parkinson’s disease (PD) to validate the Logan graphical method for quantification of ¹²³I-PE2I binding and to analyze the relationship between ¹²³I-PE2I SPECT and clinical features of this frequent degenerative disease. Methods: Eight PD patients (3 women, 5 men; mean age, 64 ± 7.9 y; disease duration range, 1–8 y, Hoehn and Yahr stage range, 1–2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 ± 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 ± 30 MBq of ¹²³I-PE2I. Results: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. ¹²³I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, ¹²³I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, ¹²³I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that ¹²³I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. Conclusion: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that ¹²³I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that ¹²³I-PE2I SPECT can be used for preclinical and early diagnosis of PD.

Key Words: Parkinson’s disease • diagnosis • SPECT • ¹²³I-PE2I • Logan plot

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