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Am J Nucl Med Mol Imaging 2013;3(2):154-165
Original Article
Organ biodistribution of Germanium-68 in rat in the presence and absence of
[68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body
radiation dosimetry
Irina Velikyan, Gunnar Antoni, Jens Sörensen, Sergio Estrada
PET-Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden; Department of Medicinal Chemistry,
Preclinical PET Platform, Uppsala University, SE-75183 Uppsala, Sweden; Department of Radiology, Oncology and Radiation
Science, Uppsala University, SE-75285 Uppsala, Sweden
Received December 14, 2012; Accepted January 4, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially
worldwide contrib-uting to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga
utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the
monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of
0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of
68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and
justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or
presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ
equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was
evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose
estimates indicated that the kidneys were the dose-limiting organs (185±54 µSv/MBq for female and 171±38 µSv/MBq for male) and
the total effective dose was 15.5±0.1 and 10.7±1.2 µSv/MBq, respectively for female and male. The results of this dosimetry study
conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without
exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. (ajnmmi1212004)
Keywords: Positron emission tomography, 68Ga, 68Ge, dosimetry, 68Ge/68Ga generator
Address correspondence to: Dr. Irina Velikyan, PET-Center, Center for Medical Imaging, Uppsala University Hospital, SE-751 85
Uppsala, Sweden. Tel: +46 (0)70 4834137; Fax: +46 (0)18 6110619; E-mail: irina.velikyan@bms.uu.se
Original Article
Organ biodistribution of Germanium-68 in rat in the presence and absence of
[68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body
radiation dosimetry
Irina Velikyan, Gunnar Antoni, Jens Sörensen, Sergio Estrada
PET-Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden; Department of Medicinal Chemistry,
Preclinical PET Platform, Uppsala University, SE-75183 Uppsala, Sweden; Department of Radiology, Oncology and Radiation
Science, Uppsala University, SE-75285 Uppsala, Sweden
Received December 14, 2012; Accepted January 4, 2013; Epub March 8, 2013; Published March 18, 2013
Abstract: Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially
worldwide contrib-uting to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga
utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the
monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of
0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of
68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and
justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or
presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ
equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was
evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose
estimates indicated that the kidneys were the dose-limiting organs (185±54 µSv/MBq for female and 171±38 µSv/MBq for male) and
the total effective dose was 15.5±0.1 and 10.7±1.2 µSv/MBq, respectively for female and male. The results of this dosimetry study
conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without
exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. (ajnmmi1212004)
Keywords: Positron emission tomography, 68Ga, 68Ge, dosimetry, 68Ge/68Ga generator
Address correspondence to: Dr. Irina Velikyan, PET-Center, Center for Medical Imaging, Uppsala University Hospital, SE-751 85
Uppsala, Sweden. Tel: +46 (0)70 4834137; Fax: +46 (0)18 6110619; E-mail: irina.velikyan@bms.uu.se
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