Generator-produced yttrium-90 for radioimmunotherapy.
Yttrium-90 is often considered to possess many favorable properties for radioimmunotherapy applications. Among these is its availability as a radionuclide generator product by decay of its parent, 90Sr. Nevertheless, most present and planned clinical trials with 90Y-labeled antibodies employ radioactivity obtained not from an in-house generator, but from commercial sources. To prepare for clinical trials at this institution with 90Y labeled to diethylenetriaminepentaacetic acid- (DTPA) coupled antibodies, we have adapted previously published procedures and have developed others to prepare antibodies labeled with generator produced 90Y for human use. Up to 25 mCi of 90Sr have been loaded without evidence of radiolytic degradation to the Dowex 50 cation exchange resin which serves as the solid support for the generator. Using 0.003M ethylenetriaminetetraacetic acid (EDTA) as eluant, elution efficiency averages 98% and 90Sr breakthrough averages 0.002%. The EDTA is destroyed remotely and the activity is dissolved in 0.5M acetate, pH 6. In this form, 90Y may be used to label DTPA-coupled proteins at specific activities of 1-3 mCi/mg (an order of magnitude improvement in specific activity results from the purification of 90Y by cation exchange prior to labeling). When properly labeled, size exclusion HPLC shows 90% or greater radiochemical purity and recovery without postlabeling purification. We conclude that these techniques provide a 90Y-labeled protein preparation which is safe for administration to patients.
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D011876:Radionuclide Generators; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes