Strategies for enhancement of radioimmunotherapy

Int J Rad Appl Instrum B. 1991;18(6):633-40. doi: 10.1016/0883-2897(91)90033-h.

Abstract

Two new strategies for increasing tumor uptake have been investigated. First the effect of interleukin-2 (IL-2) on tumor uptake of 125I-Lym-1 antibody in nude mice was investigated. Secondly, the use of 67Cu-labeled Lym-1 was evaluated in patients. In nude mice implanted with Raji human lymphoma, a greater than 2-fold enhancement of tumor uptake of 125I-Lym-1 was observed after administration of PEG-interleukin-2 (PEG-IL-2). The macrocycle 1,4,8,11-tetraazacylcotetradecane-N,N',N",N"'-tetraacetic acid (TETA), synthesized specifically for copper chelation, has been conjugated to Lym-1 for 67Cu labeling of the monoclonal antibody (MoAb). There was no evidence for bone or normal marrow uptake and the residence time in the tumor was prolonged. Surprisingly, a dose of 4.4 mCi that was intended for imaging induced substantial tumor regression in a patient.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neoplasm / immunology
  • Antibodies, Neoplasm / metabolism
  • Burkitt Lymphoma / diagnostic imaging
  • Burkitt Lymphoma / therapy
  • Chelating Agents / pharmacology
  • Copper Radioisotopes
  • Female
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacokinetics
  • Interleukin-2 / therapeutic use*
  • Iodine Radioisotopes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Radioimmunotherapy*
  • Radionuclide Imaging
  • Tumor Cells, Cultured

Substances

  • Antibodies, Neoplasm
  • Chelating Agents
  • Copper Radioisotopes
  • Heterocyclic Compounds
  • Interleukin-2
  • Iodine Radioisotopes
  • 4-bromoacetamidobenzyl-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid