Visualizing dopamine transporter integrity with iodine-123-FP-CIT SPECT in combination with high resolution MRI in the brain of the common marmoset monkey

Abstract

Considerable progress has been made in small animal single photon emission computed tomography (SPECT) imaging in the field of Parkinson's disease. In preclinical research, there is an increasing demand for in vivo imaging techniques to apply to animal models. Here, we report the first protocol for dopamine transporter (DAT) SPECT in common marmosets using the radioligand ¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane (¹²³I-FP-CIT). Serial SPECT images were obtained on an upgraded clinical scanner to determine the distribution kinetics of ¹²³I-FP-CIT in the marmoset brain. After intravenous injection of approximately 60 MBq of the radiotracer ¹²³I-FP-CIT, stable and specific striatal uptake was observed for at least 4h. Analysis of plasma samples showed rapid disappearance of the radiotracer from blood plasma within a few minutes after application, with activity declining to 4.1% of the administered activity. Structural magnetic resonance imaging (MRI) at 400 μm resolution provided the details of the underlying anatomy. In a marmoset model of Parkinson's disease, which was generated by unilateral injections of 6-hydroxydopamine (6-OHDA) into the nigro-striatal projection pathway, complete loss of striatal DAT binding in combination with behavioral deficits was observed. The presented study demonstrates that ¹²³I-FP-CIT SPECT is a suitable tool to investigate DAT integrity in preclinical studies on common marmosets.