Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and90Y-labeled 1, 4, 7, 10-tetraazacyclododecane-N, N′, N′, N‴-tetraacetic acid (DOTA)-biotin Academic Article uri icon

Overview

MeSH Major

  • Biotin
  • Immunoconjugates
  • Organometallic Compounds
  • Radioimmunotherapy
  • Radiopharmaceuticals
  • Streptavidin
  • Ytterbium

abstract

  • We investigated the biodistribution of (88)Y/(111)In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin and therapy with (90)Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis(y) antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 micro g of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 micro g of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 micro g of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of (90)Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had <2.6% of the injected dose per gram, whereas tumor uptake reached approximately 15% ID/g. The total tumor uptake of radioactivity remained similar for 96 h or longer. In the first study, the median survival of the control group was 8 days, whereas it increased to >163 days in the 37 MBq (90)Y group (P < 0.005). In a second therapy group, 7 of 10 mice receiving 37 MBq of (90)Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with

publication date

  • October 15, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 12384535

Additional Document Info

start page

  • 5755

end page

  • 60

volume

  • 62

number

  • 20