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 (â¼330 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-ß 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-ß pathology, warranting further imaging studies of zinc homeostasis in patients with AD.
Subject(s)
Alzheimer Disease/diagnostic imaging , Citrates/administration & dosage , Positron-Emission Tomography/methods , Radiopharmaceuticals/administration & dosage , Zinc Radioisotopes/chemistry , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Brain/diagnostic imaging , Brain/metabolism , Citrates/chemistry , Citrates/pharmacokinetics , Female , Fluorodeoxyglucose F18 , Healthy Volunteers , Humans , Male , Middle Aged , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution , Urine/chemistryABSTRACT
We used the systems engineering technique of discrete event simulation modeling to assist in increasing patient access to positron emission tomographic examinations in the Department of Nuclear Medicine at Mayo Clinic, Rochester. The model was used to determine the best universal slot length to address the specific access challenges of a destination medical center such as Mayo Clinic. On the basis of the modeling, a new schedule was implemented in April 2012 and our before and after data analysis shows an increase of 2.4 scans per day. This was achieved without requiring additional resources or negatively affecting patient waiting, staff satisfaction (as evaluated by day length), or examination quality.