Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac

Nucl Med Biol. 2001 Oct;28(7):845-56. doi: 10.1016/s0969-8051(01)00257-8.

Abstract

The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the alpha-chain of the IL-2 receptor (IL-2Ralpha) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211At of two new linkers, N-succinimidyl 4-[211At]astato-3-methylbenzoate and N-succinimidyl N-(4-[211At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[211At]astatobenzoate and N-succinimidyl 3-[211At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated (125I) Hu-anti-Tac. The N-succinimidyl N-(4-[211At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[125I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated (125I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer.

MeSH terms

  • Animals
  • Antibodies* / chemistry
  • Astatine*
  • Chromatography, High Pressure Liquid
  • Female
  • Indicators and Reagents
  • Isotope Labeling
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptors, Interleukin-2 / immunology*
  • Succinimides*
  • Tissue Distribution

Substances

  • Antibodies
  • Indicators and Reagents
  • N-succinimidyl N-(4-astatophenethyl)succinamate
  • Radiopharmaceuticals
  • Receptors, Interleukin-2
  • Succinimides
  • Astatine