Verschuer, J, Towson, J, Eberl, S, Katsifis, A, Henderson, D, Lam, P, Wen, L, Loc’h, C, Mattner, F, Thomson, S, Mohamed, A, & Fulham, M 2012, ‘Radiation dosimetry of the translocator protein ligands [18F]PBR111 and [18F]PBR102’, Nuclear Medicine And Biology, 39, pp. 742-753.
Associated Institution(s): Royal Prince Alfred Hospital, the University of Sydney, and ANSTO LifeSciences
The study aimed to test toxicity and metabolic properties of two radioactive molecules that may be used to identify regions of inflammation in the central nervous system (CNS) through positron emission tomography (PET scans) to potentially identify cases of neurodegenerative diseases such as multiple sclerosis.
A total of four baboons were used in this experiment, two male and two female, to test the two radioactive compounds. The first pair were aged 17 and 20 years old, and the second pair were both 9 years old. The baboons were fasted for 6 hours and anesthetised before radioactive substance injection and PET scans.
Standardised uptake values of the radioactive molecules were calculated from the scans and quantified in a number of organs including the brain, lungs, heart, liver, gallbladder, spleen, kidneys, testes, bone marrow, and bladder.
The effective dose was then calculated which gives an estimate of the health risk to the body in terms of the probability of genetic mutation or cancer initiation after exposure to a radioactive substance.
The results of the experiment were compared with previous results from a similar study in 8-10 week old Sprague-Dawley rats where the percentage of the injected dose found in the organs was calculated after the rats were killed and organs were removed for analysis.
Results and Conclusions
The study concluded that there should be no harmful tissue reaction to the radioactive compound in humans in the dose required for PET scanning purposes. Data obtained from rat experiments overestimated the dose estimates in humans compared to the baboon data.
Inappropriate Human Model
The study performs comparisons between the two mammalian species of the baboon and the rat. These comparisons confirm that there are vast differences in radioactive molecule clearance from the different animals. The study with primates claims to void results obtained from mice altogether, potentially indicating serious issues with the use of rodents as models for humans, but also brings up questions of reliability of experimental results between other mammalian species such as the baboon and the human.
The primates showed varied responses to the uptake and excretion of these substances depending on the individual. When responses can vary dramatically amongst different individuals in a population, how can these results be extrapolated to an entirely different species? The calculations used in the experiment to transfer the primate data to humans is the following simple equation:
The differences between species metabolism will be intricate and incredibly difficult to quantify, however the experiment tries to use basic math surrounding the mass of different organs and bodies to transfer the data for human use. The study itself states:
‘there are interspecies differences in the biodistribution and hence in organ doses’
‘Studies in humans, however, could provide data to check these radiation dose estimates and, in particular, determine if there are differences in excretion pathways or rates.’
The study itself indicates the need for further human studies to be conducted as they cannot determine if there will be differences in the excretion path of these molecules compared to primates. This therefore calls into question the need for any primate experimentation if the data is not confidently comparable to humans and does not erase the need for human studies. Human studies would inevitably need to be conducted with or without the additional primate experiment.
Was the study necessary?
The study was conducted in order to verify the potential use of two molecules for inflammation identification using PET scans, however, the study mentions three other ligands that have been previously identified to serve this exact purpose, in fact, these other ligands are already in clinical use. DAA1106, PBR06 and PBR28 have all been used in human studies and are successful in creating PET scans to identify CNS inflammation without any current problems. Why then is it necessary to test two entirely new radioactive molecules and put baboons through the process of this experiment when it is adding no extra benefit or medical advancement?
The baboons in this experiment were likely to have come from The National NHMRC Baboon Colony, which is funded by the National Health and Medical Research Council but managed by the Royal Prince Alfred Hospital, which is also the institute responsible for this study. This colony is maintained for animal research studies and can hold up to 165 baboons. The baboons in this experiment kept their lives, which is not the case for many others, however do they return to the colony to await their fate on the next experiment that they are selected for? How many experiments has these baboons already undergone? It is unlikely that a baboon would be kept for 20 years in such a facility without any experiments being conducted. Continual experiments throughout their lives would have a significant impact of their welfare.
This breeding institute of baboons for experimental purposes is funded by taxpayer money with a lump sum of $ 1,084,785 being awarded in 2012 as well as an added annual contribution of $195,000 from the NHMRC.
What You Can Do
Please write to the following to voice your concerns about the use of primates in unnecessary experiments. Ask how they justify the use of animals in experimental procedures when these animals do not appropriately model humans.
Animal Welfare Committee
South Western Sydney Local Health
Locked Bag 7279
Liverpool BC 1871
Royal Prince Alfred Hospital Ethics Committee