PHARMACOKINETICS AND BIODISTRIBUTION OF RADIOIMMUNOCONJUGATES OF ANTI-CD19 ANTIBODY AND SINGLE-CHAIN FV FOR TREATMENT OF HUMAN B-CELL MALIGNANCY

The comparative advantages and disadvantages of intact antibodies and single-chain Fv as immunotoxins and radioimmunoconjugates have been wi dely discussed but not directly compared. In this study, the in vivo p roperties of anti-CD19 B43 monoclonal antibody and its derived single- chain Fv (FVS191) were studied in athymic nude mice bearing CD19-posit ive human lymphomas. B43 mab and FVS191 were labeled with iodine-125 u sing iodine-beads, and immunoreactivities were determined to be 57% an d 72%, respectively. Scatchard analysis showed a similar high affinity for both. The results of pharmacokinetic studies revealed that FVS191 had a rapid biphasic clearance from the circulation (T1/2 alpha = 2.5 min, T1/2 beta = 3.7 h); The T1/2 alpha and T1/2 beta phases of B43 m ab were determined to be 0.72 h and 57 h respectively. Biodistribution studies compared the uptake of labeled antibodies by CD19-positive an d by CD19-negative tumors. The peak percentages of injected dose were 5.7% at 12 h for B43 and 2.45% at 1 h for FVS191. Radiolocalization in dices (RI) demonstrated tumor-specific uptake for both, but higher upt ake for B43. The optimal RI was seen at 15 min for FVS191 and 6 h for B43. FVS191 was unstable in vivo, approximately 50% of the injected do se being degraded in blood in 100 min. Radioactivity detected in the u rine was present mainly as the deiodinized form of FVS191. The results suggest that B43 mab is favored over FVS191 in biodistribution proper ties and in vivo stability. Because B43 Mab showed early tumor-specifi c uptake, high RI values, and favorable tissue-to-blood ratios, it is a potential candidate for radioimmunotherapy and immunotoxin therapy o f B-cell leukemia and lymphoma.