First PET imaging studies with 63Zn-zinc citrate in healthy human participants and patients with Alzheimer disease

Timothy R. DeGrado, Bradley J. Kemp, Mukesh K. Pandey, Huailei Jiang, Tina M. Gunderson, Logan R. Linscheid, Allison R. Woodwick, Daniel M. McConnell, Joel G. Fletcher, Geoffrey B. Johnson, Ronald C. Petersen, David S. Knopman, Val J. Lowe

Research output: Contribution to journalArticle

12 Scopus citations

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 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-b 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-b pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalMolecular Imaging
Volume15
DOIs
StatePublished - 2016

Keywords

  • Alzheimer disease
  • PET
  • Zinc homeostasis
  • Zn

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Fingerprint Dive into the research topics of 'First PET imaging studies with <sup>63</sup>Zn-zinc citrate in healthy human participants and patients with Alzheimer disease'. Together they form a unique fingerprint.

  • Cite this