First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease

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

doi:10.1177/1536012116673793

First PET Imaging Studies With ⁶³ Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease

Journal Article · Fri Jan 01 00:00:00 EST 2016 · Molecular Imaging

DOI:https://doi.org/10.1177/1536012116673793· OSTI ID:1423938

DeGrado, Timothy R. ^[1]; Kemp, Bradley J. ^[2]; Pandey, Mukesh K. ^[2]; Jiang, Huailei ^[2]; Gunderson, Tina M. ^[3]; Linscheid, Logan R. ^[2]; Woodwick, Allison R. ^[2]; McConnell, Daniel M. ^[2]; Fletcher, Joel G. ^[2]; Johnson, Geoffrey B. ^[2]; Petersen, Ronald C. ^[4]; Knopman, David S. ^[4]; Lowe, Val J. ^[2]

Mayo Clinic, Rochester, MN (United States). Dept. of Radiology; Mayo Clinic Rochester
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.

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Research Organization:: Mayo Clinic, Rochester, MN (United States)

Sponsoring Organization:: AVID Radiopharmaceuticals, Philadelphia, PA (United States); Elsie and Marvin Dekelboum Family Foundation; GE Healthcare, Little Chalfont (United Kingdom); National Institute on Aging; Siemens Molecular Imaging, Inc, Knoxville, TN (United States); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23). Biological Systems Science Division

Grant/Contract Number:: SC0008947

OSTI ID:: 1423938

Journal Information:: Molecular Imaging, Journal Name: Molecular Imaging Journal Issue: 1-10 Vol. 15; ISSN 1536-0121

Publisher:: SAGECopyright Statement

Country of Publication:: United States

Language:: English

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Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish Sarasamma, Sreeja; Audira, Gilbert; Juniardi, Stevhen International Journal of Molecular Sciences, Vol. 19, Issue 10 https://doi.org/10.3390/ijms19103195	journal	October 2018

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Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
63Zn
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PET
zinc homeostasis