Re Yttrium finds its way to cortical bone (yes, were the marrow lives)
It has been pointed out to me that the second part of this is incorrect. Yes, 90-Y is thought to accumulate in cortical bone, but no, the marrow resides in something called trabercular bone. Only free 90-Y, which falls off the chelating agent (CA) that sticks it to the antibody, can migrate to cortical bone. Lots of research was done to come up with the CA used in Zevalin, as to minimize this 'falling off' problem. My understanding is that this is still a problem even with the best CAs, but better by a factor of 10 or more than what people tried early on. Moreover the potential migration of 90Y from the bone surface to the trabercular section is slower than the radioactive decay itself, so it never makes it directly to where the marrow is.
Here is a detailed picture of bone structure pointing out what's called cortical and what's called trabercular: merck.com and merck.com
For definitions, see merck.com and merck.com
From recent reading I also collected that 90-Y's beta particle emission has a range of 1.1 cm; its half-life of decay (to 90-Zr) is 64.1 hours (versus 8 days for 131-I, the radioisotope in Bexxar, which is a gamma emitter).
Bottom line on the "theories"? Who knows? But clearly, my first shot was much too simplistic. I see no simple explanation a priori of why Zevalin should be more toxic to marrow than Bexxar, though the reported clinical data seems to lean that way.
PB |
