Pharmacokinetics of 111In- and 125I-labeled antiTac single-chain Fv recombinant immunotoxin

Hisataka Kobayashi, Chih Hao K. Kao, Robert J. Kreitman, Nhat Le, Meyoung Kon Kim, Martin W. Brechbiel, Chang H. Paik, Ira Pastan, Jorge A. Carrasquillo

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


The use of immunotoxins for cancer therapy is an attractive strategy that exploits the targeting specificity of monoclonal antibodies and their fragments as well as the exquisite toxicity of the toxins. However, few studies of immunotoxins have evaluated their biodistribution in vivo. Previous studies have used 125I for tracing immunotoxin biodistribution in mice. Because the immunotoxin works only when it is internalized and because of known problems with quick dehalogenation after internalization of antibodies, we decided to use 111ln, which has greater intracellular retention than iodine. Methods: To trace the in vivo pharmacokinetics of the immunotoxin in mice, we labeled the antiTac(Fv)-PE38 with 111In and compared it with 125I-labeled antiTac(Fv)-PE38. We successfully labeled antiTac(Fv)-PE38 with 111In at up to 2.96 GBq/mg. A 3- to 4-fold decrease in cytotoxicity was observed for both radiolabeled preparations. We evaluated the internalization of 111In- and 125I-labeled antiTac(Fv)PE38 into ATAC4 cells (Tac-positive) as well as their biodistribution and pharmacokinetics in vivo in mice. In addition, some mice receiving these reagents were co-infused with 30 mg L-lysine to inhibit renal accumulation. Results: Significantly more 111In- than 125l-labeled antiTac(Fv)-PE38 accumulated in the ATAC4 cells (20% versus 5% of initial surface-bound radioactivity; P < 0.001). In vivo, significantly more rain- than 125I- labeled antiTac(Fv)PE38 accumulated in the kidney (119 versus 31 percentage injected dose per gram [%ID/g]; P < 0.001). The tumor accumulation of 111In-labeled antiTac(Fv)-PE38 at 96 h was 13-fold greater than that of 125I-labeled antiTac(Fv)-PE38 (1.4 versus 0.1 %ID/g; P < 0.001). No antiTac(Fv)-PE38 was excreted into the urine in its intact form unless lysine was co-infused. Co-injected lysine reduced the renal accumulation of 111In-labeled antiTac(Fv)PE38 by 62%. Conclusion: We evaluated the biodistribution, pharmacokinetics, and catabolism of 111In-labeled antiTac(Fv)PE38 and found that it differed from 125I-labeled antiTac(Fv)PE38. These studies suggest that 111In-labeled antiTac(Fv)-PE38 can be used to trace the fate of antiTac(Fv)-PE38 in humans.

Original languageEnglish
Pages (from-to)755-762
Number of pages8
JournalJournal of Nuclear Medicine
Issue number4
Publication statusPublished - 2000 Apr
Externally publishedYes


  • I
  • Immunotoxin
  • Interleukin-2 receptor α subunit
  • Monoclonal antibody
  • ln

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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