Abstract
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Objectives Abnormalities of zinc homeostasis are indicated in many human diseases, including Alzheimer’s disease (AD). We have developed 63Zn-zinc citrate (T1/2 =38.5 min) as a PET imaging probe of zinc transport. Herein, we report a first-in-human study in healthy human subjects and patients with AD with particular attention to brain kinetics of the radiotracer.
Methods Six healthy elderly subjects and six patients with clinically confirmed AD and positive 11C-PiB scans were studied. Dynamic PET imaging of the brain was performed for 30 min following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, PET images from head to thigh were acquired out to 2 hours post-injection. Samples of urine and blood were analyzed to give information on urinary excretion, pharmacokinetics and transport into erythrocytes. Regional cerebral clearance kinetics were analyzed in relationship with available 11C-PiB and 18F-FDG imaging data.
Results 63Zn citrate was well tolerated in human subjects with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney with moderate uptake seen in intestines, prostate (males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependences were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-plaque burden (11C-PiB) and 18F-FDG hypometabolism.
Conclusions Zinc transport was successfully imaged in human subjects using the PET probe 63Zn-zinc citrate. Preliminary information on zinc kinetics in AD subjects evidenced regional differences in clearance rates in correspondence to regional amyloid-beta pathology and 18F-FDG hypometabolism, warranting further imaging studies of zinc homeostasis in AD patients.