During initial investigation on production of alpha-therapeutical agents, ran into a wall. The idea is to establish the production of 225Actinium-based compounds. But the question is what is used as a reference standard in such case ? As opposite to usual way when I can synthesize or purchase the cold reference standard, here I don't see such a possibility. Just bare assumption that 225Ac is chelated with the precursor because of no other possible products seems speculative, but literature search gives miserable-to-none information about this. How does this work with FDA in terms of IND applications and all the clinical human use regulations ? Any comments deeply appreciated
I would expect that some pseudo-carrier analog of Ac3+, e.g. Ln3+ may help you. Then the chelation yield should be determined quite easily. However, in some cases deeper analysis of the products is needed, since more types of chelates may arise.
Hi Jan,
I think the chelation yield is not a problem to determine from radio-HPLC, that's easy. As I mentally go through the process, it looks like I can perform all the necessar QC tests for clinical release, the identity is a problem. I mean, 18F-FLT is co-injected with 19F-FLT and we show that's it. Same for Y, Ga, Lu -stuff. But there is no 'cold' actinium, that's a problem. I was thinking about substitute, based on 9-2 orbitals, maybe Y or Sc and make the cold standard with the hope that all the metal complexes will appear with the same Rt in HPLC, so that I can co-inject 225Ac stuff with it. But how to validate this approach? My main concern for clinical production is how to deal with FDA in this case, when they question me "How do you know your stuff is indeed what you want ? What is the validated proof ?". Obviously, there is no option to make cold standard for Actinium drugs, so there should be some specific procedure for regulatory paperwork in this case, but absolutely not obvious to me from their website or documentation :(
Ján Kozempel's response of using a similar Ln3+ is spot on. That is what you would do... You could use Sc, or Y however I think using an element with f-orbitals (e.g. Ln3+) similar to Actinium would be the better and proper route.
Hi Anthony,
Thanks for your answer, this is what I am thinking about as of now, Ian's suggestion about La looks the best option for the closest element, but still the same question is open - how will FDA look at it ? Actually, since you are from the Tri-Lab and I know A LOT of different stuff is done there - do you guys have any hands-on experience with filing this type of compounds to FDA ?
We do dabble a lot with Actinium production (not me specifically) but we are more in the production of radiopharmaceuticals and not the synthesis side of radiopharmaceutical (which is where the FDA and you are concerned). So, we don't do a lot of FDA work with it currently (or maybe ever). Possibly in the future when the production ramps up more?
Pity :( Will keep searching for more info while our authorities decide whether they want alpha-therapy here or not :)
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