Biodistribution and Radiation Dosimetry of the Vesicular Monoamine Transporter Type 2 Ligand [18F]-AV133 in rats

Autor: Ko Ting Chao, 趙可婷
Rok vydání: 2010
Druh dokumentu: 學位論文 ; thesis
Popis: 98
英文摘要 Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the endocrine cells and brain. 18F-labeled derivatives of dihydrotetrabenazine (DTBZ) will improve the VMAT2 image in clinical setting instead of 11C-labeled derivatives. To further facilitate its future utilization in clinical trials. In the present study, we investigated the biodistribution and radiation dosimetry of 18F-FP-(+)-DTBZ or 18F-AV-133 using animal PET. Five male Wistar rats were used in the biodistribution study. Six-hour dynamic whole-body animal PET/CT images were acquired immediately after intravenous injection of 25.7 ± 3.09 MBq 18F-AV-133. The co-registrated PET/CT images were displayed and analyzed using the PMOD image analysis workstation. Volume of interests including brain, lungs, heart, liver, stomach, pancreas, intestine, kidneys, bladder, testes, red bone marrow and whole body were manually delineated on the fused PET/CT images. The animal biodistribution data expressed as the percentage of injected dose (%ID) was extrapolated to model human organs (i.e., Standard Man) according to each organ weight. The OLINDA/EXM application was used to determine the effective doses (EDs) for individual organ. The standard uptake value ratio (SUVR) of region striatum and brainstem to cerebellum were also been evaluated in another dynamic PET study. The high-absorbed doses were found in the upper large intestine wall, small intestine, liver and pancreas. The critical organ was the upper large intestine wall which received 53.8±2.28 μGy/MBq. The effective dose equivalent and effective dose were 24.9±0.5 μSv/MBq and 20.6±0.5 μSv/MBq, respectively. These data are similar to those reported in human, which were 36.5±2.8 μSv/MBq and 27.8±2.5 μSv/MBq, respectively, and comparable to other 18F-labeled radiopharmaceuticals reported in the literatures. SUVR of striatum and brainstem to cerebellum reached the plateau 8.04±1.3 around 105 minutes and 4.68±1.1 around 85 minutes after injection, respectively. 18F-AV-133 demonstrated appropriate biodistribution and radiation dosimetry for imaging VMAT2 sites in rats. The results showed that small-animal PET presents an opportunity for providing radiation dose estimates with statistical and logistical advantages.
Databáze: Networked Digital Library of Theses & Dissertations