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 »
- Authors:
-
- 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
- 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}
}
Web of Science
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