RT Journal Article SR Electronic T1 In Vivo Dopamine Transporter Imaging in a Unilateral 6-Hydroxydopamine Rat Model of Parkinson Disease Using 11C-Methylphenidate PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 813 OP 822 DO 10.2967/jnumed.111.101436 VO 53 IS 5 A1 Vesna Sossi A1 Katherine Dinelle A1 Salma Jivan A1 Kristina Fischer A1 James E. Holden A1 Doris Doudet YR 2012 UL http://jnm.snmjournals.org/content/53/5/813.abstract AB Dopamine transporter (DAT) function is altered by many neurodegenerative diseases. For instance, in Parkinson disease DAT density has been shown to decrease in early disease and to play a role in the occurrence of motor complications. DAT is thus an important imaging target with potential therapeutic relevance in humans and animal models of disease. The PET DAT marker 11C-methylphenidate is commonly used to quantify DAT function. Here we investigate the characteristics of the 11C-methylphenidate–derived quantification of DAT in rodents using the 6-hydroxydopamine Parkinson disease rat model. Methods: Seven unilaterally 6-hydroxydopamine–lesioned rats (dopaminergic denervation [DD] range, 36%–94%) were injected with 3.7 MBq/100 g of body weight and tracer masses ranging from 93.8 to 0.0041 μg/100 g of body weight. We evaluated the maximum available transporter density and the in vivo (apparent) ligand-transporter dissociation constant (Bmax and Kdapp, respectively) with an in vivo Scatchard method using several modeling approaches and estimated the transporter occupancy as a function of the amount of tracer injected and tracer specific activity (SA). Results: Strong evidence of different nonspecific binding in the striatal region, compared with the reference region, leading to bias in the estimate of DD severity was found. One percent transporter occupancy was reached with 0.14 μg of tracer/100 g of body weight, corresponding to an SA of 5.7 kBq/pmol for the given radioactivity dose, and 10% occupancy was reached at 1.5 μg of tracer/100 g of body weight, corresponding to an SA of 0.57 kBq/pmol. The 6-hydroxydopamine lesion affected Bmax (control, 402 ± 94 pmol/mL; lesioned, 117 ± 120 pmol/mL; P = 0.003) but not Kdapp (control, 331 ± 63 pmol/mL; lesioned, 362 ± 119 pmol/mL; P = 0.63). Conclusion: Although DAT imaging can be performed at a relatively high mass of 11C-methylphenidate (low SA), the additional nonspecific binding found in the striatum can introduce a DD severity–dependent bias in the estimate of tissue-derived binding potential and care must be taken in comparing 11C-methylphenidate–derived assessment of DD with that obtained using other dopaminergic tracers.