Abstract
Background[18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared.MethodsTwenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors.ResultsBased on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation.ConclusionsThis first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666.
Highlights
Epilepsy is a chronic neurological disorder characterized by seizures and abnormal electroencephalographic activity
The aims of this study were to predict the radiation dose given to humans based on the distribution of [18F]UCB-H in mice and to determine the maximum injectable dose according to radiation guidelines in biomedical research
In this study, it was shown that the novel synaptic vesicle protein 2A (SV2A) radiotracer [18F]UCB-H meets the standard regulations regarding radiation dose for use in human clinical trials
Summary
Epilepsy is a chronic neurological disorder characterized by seizures and abnormal electroencephalographic activity. A prerequisite to the use of a novel radiotracer in human clinical trials and good clinical practice is a preclinical dosimetry study in animals. This enables the prediction of dose limits in humans that will keep radiation doses below harmful limits while still producing diagnostically beneficial images. Radiation estimates for humans derived from small animals are traditionally obtained by ex vivo tissue distribution (TD) studies, where organs are harvested post-injection at several time points to establish the biodistribution. Dynamic imaging approaches in small animals using microPET are a promising alternative, because the complete biodistribution of the radiopharmaceutical can be obtained within a single in vivo scan with a much higher time resolution. The TD and microPET approaches to assess the biodistribution were investigated and compared
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