Abstract
BackgroundWe measured whole body distribution of 11C-BU99008, a new PET biomarker for non-invasive identification of the imidazoline2 binding site. The purpose of this phase I study was to evaluate the biodistribution and radiation dosimetry of 11C-BU99008 in healthy human subjects.MethodsA single bolus injection of 11C-BU99008 (296 ± 10.5 MBq) was administered to four healthy subjects who underwent whole-body PET/CT over 120 min from the cranial vertex to the mid-thigh. Volumes of interest were drawn around visually identifiable source organs to generate time-activity curves (TAC). Residence times were determined from time-activity curves. Absorbed doses to individual organs and the whole body effective dose were calculated using OLINDA/EXM 1.1 for each subject.ResultsThe highest measured activity concentration was in the kidney and spleen. The longest residence time was in the muscle at 0.100 ± 0.023 h, followed by the liver at 0.067 ± 0.015 h and lungs at 0.052 ± 0.010 h. The highest mean organ absorbed dose was within the heart wall (0.028 ± 0.002 mGy/MBq), followed by the kidneys (0.026 ± 0.005 mGy/MBq). The critical organ was the heart wall. The total mean effective dose averaged over subjects was estimated to be 0.0056 ± 0.0004 mSv/MBq for an injection of 11C-BU99008.ConclusionsThe biodistribution of 11C-BU99008 has been shown here for the first time in humans. Our dosimetry data showed the total mean effective dose over all subjects was 0.0056 ± 0.0004 mSv/MBq, which would result in a total effective dose of 1.96 mSv for a typical injection of 350 MBq of 11C-BU99008. The effective dose is not appreciably different from those obtained with other 11C tracers.
Highlights
We measured whole body distribution of 11C-BU99008, a new PET biomarker for non-invasive identification of the imidazoline2 binding site
The density of imidazoline2 binding site (I2BS) has been shown to increase in Alzheimer’s disease (AD) postmortem [2], and it has been suggested that I2BS may be a marker for the severity and malignancy of human glioblastomas [9]
The fact that I2BS is increased in postmortem AD brains and that they are located on astrocytes mean that a radioligand that binds to the I2BS may prove to be a very useful research tool for understanding both the role of I2BS and the astrocytic arm of the neuroinflammatory process in AD [10,11,12,13,14,15]
Summary
We measured whole body distribution of 11C-BU99008, a new PET biomarker for non-invasive identification of the imidazoline binding site. The purpose of this phase I study was to evaluate the biodistribution and radiation dosimetry of 11C-BU99008 in healthy human subjects. The fact that I2BS is increased in postmortem AD brains and that they are located on astrocytes mean that a radioligand that binds to the I2BS may prove to be a very useful research tool for understanding both the role of I2BS and the astrocytic arm of the neuroinflammatory process in AD [10,11,12,13,14,15]. A previous investigation of the distribution of this PET radioligand was performed in healthy rhesus monkeys in order to determine a safe dose of radiation to human subjects following administration of 11C-BU99008 (unpublished data). The aim of the present phase I study was to determine this data using PET imaging of healthy volunteers using radiodosimetry
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