Biotech Values

[bobrmd]

There are several problems with radiolabeled antibodies. The first is that there is non specific uptake of the antibody by the reticuloendothelial system. If you inject an antibody the fc end of the antibody binds to tissue. You will find significant uptake in bone marrow, spleen liver lung. Even if you slice off the fc end of the antibody you will still see nonspecific uptake. So antibodies are really not magic bullets. There is non specific uptake and then degredation and clearance from he body all of which results in dose deposited in normal tissues.

The second reason is the energy characteristics of the isotope itself. The number of isotopes which can be placed on the antibody are limited. The two most common ones are yitrium and iodine 131. In the case of iodine the gamma energy contributes little to the dose on a microscopic level and the beta energy is high enough that the path length is long so little dose is actually deposied compared to a situation where you have a macroscopic tumor. yitrium again has the same beta problem.

So the problems are twofold, nonspecific uptake and the absorbed dose in microscopic environment. Furhtermore factors such as blood flow and necrosis influence antibody distribution.

The end result is that there is only a small gain in dose delivery to a tumor say 2-5 fold over critical normal tissues. So in the case of bone marrow, it is wiped out by as little as 150cgy wheras the dose to control a solid tumor is in the order of thousands of cgy.