Comparative biodistribution studies of DTPA-derivative bifunctional chelates for radiometal labeled monoclonal antibodies.

Biodistribution of five different backbone-substituted derivatives of SCN-Bz-DTPA (1B4M-DTPA, 1M3B-DTPA, 1B3M-DTPA, GEM-DTPA and 2B-DTPA) linked to MAb B72.3 were compared to that of the parent molecule after labeling with 111indium. Athymic mice, bearing human colon carcinoma xenografts (LS-174T) were injected i.v. to determine the biodistribution of the MAb chelate conjugates. Three of the MAb metal chelate conjugates (1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA), labeled with 111In showed efficient and stable tumor localization as well as a slower blood clearance rate than SCN-Bz-DTPA, GEM-DTPA or 2B-DTPA MAb chelate conjugates. Major differences were also seen in normal organ uptake, especially liver and spleen. Tumor-to-liver ratios rose as a function of time for 1B4M-DTPA, 1M3B-DTPA and 1B3M-DTPA MAb chelate conjugates with virtually no accumulation of the radiometal into this organ, as revealed by no increase in the liver-to-blood values. Small accretion in normal liver was noted for SCN-Bz-DTPA, GEM-DTPA or 2B-DTPA MAb chelate conjugates. The results reviewed here, and described previously (Roselli et al., 1991) demonstrate that the use in vivo of backbone-substituted forms of the SCN-Bz-DTPA, such as 1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA bound to MAbs, can reduce uptake of indium to normal organs while maximizing the dose to tumor.
AuthorsM Roselli, J Schlom, O A Gansow, M W Brechbiel, S Mirzadeh, C G Pippin, D E Milenic, D Colcher
JournalInternational journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology (Int J Rad Appl Instrum B) Vol. 18 Issue 4 Pg. 389-94 ( 1991) ISSN: 0883-2897 [Print] UNITED STATES
PMID1864727 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Chelating Agents
  • Indium Radioisotopes
  • Pentetic Acid
  • Animals
  • Antibodies, Monoclonal (pharmacokinetics)
  • Chelating Agents (pharmacokinetics)
  • Colonic Neoplasms (metabolism)
  • Indium Radioisotopes
  • Kidney (metabolism)
  • Liver (metabolism)
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Pentetic Acid (pharmacokinetics)
  • Spleen (metabolism)

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