Imaging phosphodiesterase-10a availability in cocaine use disorder with [¹¹ C]IMA107 and PET

Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self-administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder ("cocaine users") compared to controls. PDE10a availability was measured with [¹¹ C]IMA107 and positron emission tomography in 15 cocaine users and 15 controls matched for age, gender, and nicotine status. Cocaine users with no comorbid psychiatric, medical, or drug abuse disorders were scanned following two weeks of outpatient-monitored abstinence. [¹¹ C]IMA107 binding potential relative to nondisplaceable uptake (BP_ND ) in the regions of interest was derived with the simplified reference tissue method. No significant effect of diagnosis on BP_ND was demonstrated using linear mixed modeling with [¹¹ C]IMA107 BP_ND as the dependent variable and regions of interest as a repeated measure. There were no significant relationships between BP_ND and clinical rating scales. To the extent that PDE10a is a valid proxy for MSN spine density, these results do not support its increase in recently abstinent cocaine users.