Effects of radiolysis on yttrium-90-labeled Lym-1 antibody preparations

The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90Y-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem.

Lym-1-21T-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-21T-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA overall; all were monitored as above.

The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (> or = 80%) as was their immunoreactivity (> or = 75%) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate.

Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y-21T-BAD-Lym-1 products < or = 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.