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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

Positron emission tomography
citrates
Citric Acid
Positron-Emission Tomography
Zinc
positrons
Healthy Volunteers
Alzheimer Disease
tomography
zinc
Imaging techniques
clearances
homeostasis
glands
Fluorodeoxyglucose F18
hypometabolism
brain
Brain
digestive system
Homeostasis

Keywords

  • Zn
  • Alzheimer disease
  • PET
  • Zinc homeostasis

ASJC Scopus subject areas

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

Cite this

First PET imaging studies with 63Zn-zinc citrate in healthy human participants and patients with Alzheimer disease. / DeGrado, Timothy R; Kemp, Bradley J.; Pandey, Mukesh; Jiang, Huailei; Gunderson, Tina M.; Linscheid, Logan R.; Woodwick, Allison R.; McConnell, Daniel M.; Fletcher, Joel Garland; Johnson, Geoffrey B.; Petersen, Ronald Carl; Knopman, David S; Lowe, Val.

In: Molecular Imaging, Vol. 15, 2016, p. 1-10.

Research output: Contribution to journalArticle

DeGrado, Timothy R ; Kemp, Bradley J. ; Pandey, Mukesh ; Jiang, Huailei ; Gunderson, Tina M. ; Linscheid, Logan R. ; Woodwick, Allison R. ; McConnell, Daniel M. ; Fletcher, Joel Garland ; Johnson, Geoffrey B. ; Petersen, Ronald Carl ; Knopman, David S ; Lowe, Val. / First PET imaging studies with 63Zn-zinc citrate in healthy human participants and patients with Alzheimer disease. In: Molecular Imaging. 2016 ; Vol. 15. pp. 1-10.
@article{e63edd7fdf0c47e8b50e8f2fde9508bb,
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 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.",
keywords = "Zn, Alzheimer disease, PET, Zinc homeostasis",
author = "DeGrado, {Timothy R} and Kemp, {Bradley J.} and Mukesh Pandey and Huailei Jiang and Gunderson, {Tina M.} and Linscheid, {Logan R.} and Woodwick, {Allison R.} and McConnell, {Daniel M.} and Fletcher, {Joel Garland} and Johnson, {Geoffrey B.} and Petersen, {Ronald Carl} and Knopman, {David S} and Val Lowe",
year = "2016",
doi = "10.1177/1536012116673793",
language = "English (US)",
volume = "15",
pages = "1--10",
journal = "Molecular Imaging",
issn = "1535-3508",
publisher = "Decker Publishing",

}

TY - JOUR

T1 - First PET imaging studies with 63Zn-zinc citrate in healthy human participants and patients with Alzheimer disease

AU - DeGrado, Timothy R

AU - Kemp, Bradley J.

AU - Pandey, Mukesh

AU - Jiang, Huailei

AU - Gunderson, Tina M.

AU - Linscheid, Logan R.

AU - Woodwick, Allison R.

AU - McConnell, Daniel M.

AU - Fletcher, Joel Garland

AU - Johnson, Geoffrey B.

AU - Petersen, Ronald Carl

AU - Knopman, David S

AU - Lowe, Val

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Zn

KW - Alzheimer disease

KW - PET

KW - Zinc homeostasis

UR - http://www.scopus.com/inward/record.url?scp=85016124446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016124446&partnerID=8YFLogxK

U2 - 10.1177/1536012116673793

DO - 10.1177/1536012116673793

M3 - Article

C2 - 27941122

AN - SCOPUS:85016124446

VL - 15

SP - 1

EP - 10

JO - Molecular Imaging

JF - Molecular Imaging

SN - 1535-3508

ER -