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Title: First PET Imaging Studies With 63 Zn-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. 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 gastrointestinalmore » 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.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1];  [1];  [1];  [3];  [3];  [1]
  1. Mayo Clinic, Rochester, MN (United States). Dept. of Radiology
  2. Mayo Clinic, Rochester, MN (United States). Dept. of Health Sciences Research
  3. Mayo Clinic, Rochester, MN (United States). Dept. of Neurology
Publication Date:
Research Org.:
Mayo Clinic, Rochester, MN (United States)
Sponsoring Org.:
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)
OSTI Identifier:
1423938
Grant/Contract Number:  
sc0008947; AG16574
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Molecular Imaging
Additional Journal Information:
Journal Volume: 15; Journal Issue: 1-10; Journal ID: ISSN 1536-0121
Publisher:
SAGE
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 63Zn; PET; zinc homeostasis; Alzheimer disease

Citation Formats

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., and Lowe, Val J. First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease. United States: N. p., 2016. Web. doi:10.1177/1536012116673793.
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. First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease. United States. https://doi.org/10.1177/1536012116673793
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., and Lowe, Val J. 2016. "First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease". United States. https://doi.org/10.1177/1536012116673793. https://www.osti.gov/servlets/purl/1423938.
@article{osti_1423938,
title = {First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease},
author = {DeGrado, Timothy R. and Kemp, Bradley J. and Pandey, Mukesh K. and Jiang, Huailei and Gunderson, Tina M. and Linscheid, Logan R. and Woodwick, Allison R. and McConnell, Daniel M. and Fletcher, Joel G. and Johnson, Geoffrey B. and Petersen, Ronald C. and Knopman, David S. and Lowe, Val J.},
abstractNote = {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.},
doi = {10.1177/1536012116673793},
url = {https://www.osti.gov/biblio/1423938}, journal = {Molecular Imaging},
issn = {1536-0121},
number = 1-10,
volume = 15,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2016},
month = {Fri Jan 01 00:00:00 EST 2016}
}

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Cited by: 17 works
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Abnormal zinc metabolism in type II diabetes mellitus
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Zinc homeostasis in the metabolic syndrome and diabetes
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Zinc and insulin in pancreatic beta-cells
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ZIP14 Zinc Transporter Downregulation and Zinc Depletion in the Development and Progression of Hepatocellular Cancer
journal, March 2011


Abnormal zinc metabolism in type II diabetes mellitus
journal, August 1983


Alzheimer's disease diagnosis in individual subjects using structural MR images: Validation studies
journal, February 2008


Therapeutics for Alzheimer’s disease based on the metal hypothesis
journal, July 2008


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Mo2111 Vitamin and Mineral Status Pre and Post Treatment in Patients With Inflammatory Bowel Disease
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journal, March 2013


Urine and Serum Zinc Abnormalities in Disease of the Liver
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Biochemistry of Amyloid  -Protein and Amyloid Deposits in Alzheimer Disease
journal, February 2012


Rapid induction of Alzheimer A beta amyloid formation by zinc
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Zinc Competition among the Intestinal Microbiota
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Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis
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Pancreatic Secretion of Zinc and Copper in Normal Subjects and in Patients with Chronic Pancreatitis
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Zinc Supplementation in Public Health
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Elevated cortical zinc in Alzheimer disease
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Preparation and Preliminary Evaluation of 63Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc
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Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma
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Status of Essential Trace Minerals and Oxidative Stress in Viral Hepatitis C Patients with Nonalcoholic Fatty Liver Disease
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Diet, nutrient deficiency and chronic pancreatitis
journal, June 2013


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