Pharmacokinetics and biodistribution of radioimmunoconjugates of anti-CD19 antibody and single-chain Fv for treatment of human B-cell Malignancy |
| |
Authors: | Quanzhi Li Wendy Hudson Duo Wang Erica Berven Fatih M Uckun John H Kersey |
| |
Institution: | (1) Cancer Center, Department of Pediatrics and Laboratory Medicine/Pathology, University of Minnesota, MN 55455, USA, US;(2) Biotherapy Institute, University of Minnesota, MN 55455, USA, US |
| |
Abstract: | The comparative advantages and disadvantages of intact antibodies and single-chain Fv as immunotoxins and radioimmunoconjugates
have been widely discussed but not directly compared. In this study, the in vivo properties of anti-CD19 B43 monoclonal antibody
and its derived single-chain Fv (FVS191) were studied in athymic nude mice bearing CD19-positive human lymphomas. B43 mab
and FVS191 were labeled with iodine-125 using iodine-beads, and immunoreactivities were determined to be 57% and 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 (T1/2α = 2.5 min, T1/2β = 3.7 h); The T1/2α and T1/2β phases of B43 mab were
determined to be 0.72 h and 57 h respectively. Biodistribution studies compared the uptake of labeled antibodies by CD19-positive
and 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 indices (RI) demonstrated tumor-specific uptake for both, but higher uptake 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 dose being degraded
in blood in 100 min. Radioactivity detected in the urine was present mainly as the deiodinized form of FVS191. The results
suggest that B43 mab is favored over FVS191 in biodistribution properties and in vivo stability. Because B43 Mab showed early
tumor-specific uptake, high RI values, and favorable tissue-to-blood ratios, it is a potential candidate for radioimmunotherapy
and immunotoxin therapy of B-cell leukemia and lymphoma.
Received: 17 June 1997 / Accepted: 17 June 1998 |
| |
Keywords: | Anti-CD19 Single-chain Fv Radioimmunoconjugates Pharmacokinetics Biodistribution |
本文献已被 SpringerLink 等数据库收录! |
|