Advantage of lutetium-177 versus radioiodine immunoconjugate in targeted radionuclide therapy of b-cell tumors

Anticancer Res. 2014 Jul;34(7):3263-9.

Abstract

Background: We herein report a comparison of the radiolabels 177Lu and 125I bound to the monoclonal antibody HH1 that targets the CD37 antigen expressed on non-Hodgkin B-cell lymphomas.

Materials and methods: Mixtures of 177Lu and 125I-labeled HH1 antibody were co-injected into nude mice carrying Ramos xenografts and the biodistribution using the paired label format allowing tracer comparisons in each individual mouse.

Results: Products of the two radionuclides had very similar immunoractivity in vitro but showed different properties in vivo. Both products had relevant stability in blood and most normal tissues in nude mice carrying subcutaneous Ramos xenografts. However, both the tumor uptake and retention were significantly higher for 177Lu vs. 125I labeled HH1. The tumor to normal tissue ratios were several-fold improved for 177Lu compared to radioiodine labeled antibodies.

Conclusion: The data presented herein support the evaluation of CD37 as a target for clinical 177Lu-based radioimmunotherapy against b-cell malignancies.

Keywords: 177Lu; non-Hodgkin lymphoma; radioimmunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Neoplasm / immunology
  • Female
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Immunotoxins / pharmacokinetics
  • Immunotoxins / pharmacology*
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / pharmacology*
  • Lutetium / pharmacokinetics
  • Lutetium / pharmacology*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / radiotherapy*
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy
  • Radioimmunotherapy / methods
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / pharmacology*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / pharmacology*
  • Tetraspanins / immunology
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • CD37 protein, human
  • Heterocyclic Compounds, 1-Ring
  • Immunotoxins
  • Iodine Radioisotopes
  • Radioisotopes
  • Radiopharmaceuticals
  • Tetraspanins
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Lutetium