First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease
- Mayo Clinic, Rochester, MN (United States). Dept. of Radiology
- Mayo Clinic, Rochester, MN (United States). Dept. of Health Sciences Research
- Mayo Clinic, Rochester, MN (United States). Dept. of Neurology
Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.
- Research Organization:
- Mayo Clinic, Rochester, MN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institute on Aging; Elsie and Marvin Dekelboum Family Foundation; GE Healthcare, Little Chalfont (United Kingdom); Siemens Molecular Imaging, Inc, Knoxville, TN (United States); AVID Radiopharmaceuticals, Philadelphia, PA (United States)
- Grant/Contract Number:
- sc0008947; AG16574
- OSTI ID:
- 1423938
- Journal Information:
- Molecular Imaging, Vol. 15, Issue 1-10; ISSN 1536-0121
- Publisher:
- SAGECopyright Statement
- Country of Publication:
- United States
- Language:
- English
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