A couple of radiotracers we developed (C-11 and F-18 labeled) undergo extensive metabolism (less than 10 % intact tracer after 30 min pi). However, the radiometabolites didn't cross the BBB (hence no effect on the image acquired). In biodistributions study, we were also able to block 70 % to 90 % of the binding of the radiotracers in the target organ at 30 min pi with a structurally unrelated/different and validated compound. Hence, this rules out the contribution (significant) radiometabolites on the observed retention of radioactivity in the target organs.
Here is the problem. Can this be considered a significant drawback of the radiotracers as a potential PET tracers? Could anyone give me a feedback on this (including citation will be a plus).
Any help is greatly appreciated.
My question is whether extensive metabolism of radiotracers can be considered a significant drawback even if the radio metabolites don't affect the PET image acquired
You would need to establish how the metabolite formation is influenced by other factors.
I have worked on a tracer (11C-SA4503) which has low (but not as low as in your case) intact parent at 90min, and the metabolite does not cross BBB. The metabolite formation was influenced, at least preclinically, by various factors- age, treatment, species under consideration etc. This meant that kinetic modelling and metabolite correction was required for every study, which is not ideal as you can imagine. Metabolite correction is not exactly something you would want to do regularly in clinic, but if there are no better tracers for that particular purpose it will be used anyway. If another tracer comes along that does not require metabolite correction, but is otherwise similar, that would be preferred.
Hi,
in the brain, I think it may not hurt - if the signal from the vessels stay below the target uptake. It differs for organs which are more vascularized. Take 13-N ammonia as perfusion agent as an example. There, the metabolites contribute quite a bit to the background. But even there, it did not really stop us from using it clinically as the advantages outweigh this.
Best regards
Stephan
- Badges
- Science topic
- Similar topics
- Biological Science
- Bioecology
- Systems Ecology
- Landscape Ecology
- Connectivity