What is Pretargeted radioimmunotherapy (RIT)?

[Guest guest]

One definition is provided here:

http://www.liebertonline.com/doi/abs/10.1089/cbr.2005.20.379?journalCode=cbr

copying: " Pretargeted radioimmunotherapy (RIT) increases the dose of

radionuclide delivered to tumor sites while limiting radiation to normal

tissues. "

==

Some approaches to this basic goal have been easier for me to understand than

others. By the definition above, it appears that the current RIT protocols

incorporate the principle: cold (unlabeled antibody) is given first, which

deletes normal b-cells, so that the hot (radiolabeled) dose is more focused on

remaining tumor cells.

Also, so called dosiemetric dosing, helps to identify a dose that is based on

how fast or slow individuals clear the antibody. In the bexxar dosimetric dose,

gallium isotope is bound to the antibody, which allows cameras to measure

individual clearance rates so that the patient does not get too much or too

little of the final hot dose. (BTW: this dose-finding part of the protocol is

likely to be therapeutic as well).

Another pretarget strategy is to clear the normal b-cells with a non-competing

antibody, such as ant-cd22, so that hot dose delivered with cd20 antibody will

bind to all the cd20 receptors on each tumor cell, some of which would be taken

up by the cold antibody if the same antibody is used for the cold and hot dose.

Another is to target receptors on b-cells that internalize the antibody, so that

the radiation component is less likely to impact normal bystander cells.

PS. I'm not sure that the bystander cells are alway innocent bystanders ... a

prevailing theory being that the microenvironement promotes malignancy. So this

could be a good or bad effect.

Also, pretreatment with chemo is a probable way to maximize the effect of RIT on

tumors and reduce risk to normal cells: by reducing tumor burden so that all

tumor cells are more likely to receive a therapeutice dose of antibody and by

reducing bone marrow involvement to reduce exposure to normal stem cells in that

vital organ.

As noted up front, there are some pretarget strategies that I could not follow

or understand as described in the papers.

Karl

Patients Against Lymphoma

www.lymphomation.org