Organ biodistribution of Germanium-68 in rat in the presence and absence of [(68)Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

Positron Emission Tomography (PET) and in particular gallium-68 ((68)Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of (68)Ga 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 (68)Ga applications and that is the limit of 0.001% of Germanium-68 ((68)Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of (68)Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the (68)Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [(68)Ge]GeCl4 in the absence or presence of [(68)Ga]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). (68)Ge(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 (68)Ge(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.