Poster (Scientific congresses and symposiums)
Dosimetry for 6-[18F]Fluoro-L-DOPA in humans based on in vivo microPET scans and ex vivo tissue distribution in mice
Bretin, Florian; Warnock, Geoffrey; Bahri, Mohamed Ali et al.
2012World Molecular Imaging Congress
 

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Abstract :
[en] Radiation dosimetry of new radiopharmaceuticals generally starts with studies in small animals such as mice and rats. The traditional technique has long been ex vivo measurement of the biodistribution over time using harvested organs at different times post administration of the radiopharmaceutical. Since this approach requires a significant amount of animals, dynamic microPET studies, where the biodistribution of the tracer over time can be determined in vivo in a single scan, are an invaluable alternative. Due to known imaging artifacts and limitations, such as partial volume effect, a hybrid technique combining harvesting organs (post-scan) and dynamic imaging was introduced to achieve a cross-calibration to account for these limitations. Since 6-[18F]Fluoro-L-DOPA is a widely used PET tracer to study the dopaminergic system in neurology and oncology and there is no sound published dosimetry data, absorbed doses for major organs in humans were estimated using the traditional ex vivo technique and by dynamic microPET imaging in mice, allowing direct comparison of the results from the two techniques. The tissue distribution over time of 6-[18F]Fluoro-L-DOPA was determined by radioassay of harvested organs at 2, 5, 10, 30, 60, 120 minutes post administration (n=5 at each time point) in isoflurane-anaesthetized mice. Dynamic PET images were acquired with a FOCUS 120 microPET for 120 minutes after injection of 6-[18F]Fluoro-L-DOPA followed by radioassay of harvested organs (n=4). A bladder voiding scenario was used to simulate excretion every 2 h. The organ time-activity-curves (TACs) from both methods were extrapolated from a simulated 35 g standard mouse to a 70 kg standard male human using a technique based on organ to bodyweight ratios. The absorbed doses in major human organs were calculated with the commercially available human dosimetry software OLINDA/EXM (Version 1.1) using the extrapolated TACs. The extrapolated organ TACs obtained using the two methods showed a high correlation (average r = 0.94 ± 0.05, p < 0.001). However, TACs from PET alone under- or overestimated the activity in individual organs in contrast to TACs obtained using the cross-calibration of the PET data with the activity in post-scan dissected organs. Those organs in the excretion pathways, comprising bladder wall, kidneys and liver, received the highest organ doses. The total body absorbed dose was 0.0118 mGy/MBq for both the imaging based and harvesting based methods. The effective dose was 0.0193 mSv/MBq for the hybrid imaging-harvesting technique and 0.0189 mSv/MBq for the pure harvesting technique. Scaling errors in the PET TACs are likely caused by quantification errors such as partial volume effects and image artifacts. The use of a hybrid imaging technique to cross-calibrate the TACs improved the accuracy of the imaging-based dosimetry estimates. Therefore the hybrid technique combining dynamic imaging and harvesting organs (post-scan) is a suitable alternative to the gold standard ex vivo radioassay method. It yields comparable results yet reduces significantly the amount of animals needed in the study and can accelerate data acquisition.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bretin, Florian ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Warnock, Geoffrey ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Bahri, Mohamed Ali  ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Libert, Lionel ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Lemaire, Christian ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Phillips, Christophe  ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Seret, Alain ;  Université de Liège - ULiège > Département de physique > Imagerie médicale expérimentale
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Plenevaux, Alain  ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Language :
English
Title :
Dosimetry for 6-[18F]Fluoro-L-DOPA in humans based on in vivo microPET scans and ex vivo tissue distribution in mice
Publication date :
September 2012
Number of pages :
A0
Event name :
World Molecular Imaging Congress
Event organizer :
World Molecular Imaging Society
Event place :
Dublin, Ireland
Event date :
04/09/2012 - 08/09/2012
Audience :
International
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
The Marie Curie Initial Training Network
Available on ORBi :
since 30 August 2012

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