title: First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease.
abstract: 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. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of63Zn-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 cerebral63Zn clearances were compared with11C-Pittsburgh Compound B (11C-PiB) and18F-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 in63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden (11C-PiB) and18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe63Zn-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.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA degrado.timothy@mayo.edu.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: DeGrado
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Kemp
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Huailei
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Gunderson
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Logan R
authors.initials: LR
authors.lastname: Linscheid
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Woodwick
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: McConnell
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Fletcher
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Johnson
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002951:Citrates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D019788:Fluorodeoxyglucose F18; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry; D015037:Zinc Radioisotopes / Q000737:chemistry*
chemical_list: D002951:Citrates; D019275:Radiopharmaceuticals; D015037:Zinc Radioisotopes; D019788:Fluorodeoxyglucose F18
keywords: 
  63Zn; Alzheimer disease; PET; zinc homeostasis