Optimization of the preparation of 99mTc-labeled Hynic-derivatized Annexin V for human use

Nucl Med Biol. 2003 Oct;30(7):771-8. doi: 10.1016/s0969-8051(03)00056-8.

Abstract

Hydrazino nicotinate (Hynic) is one of the most attractive bifunctional agents designed for the labeling of proteins with (99m)Tc. Recently, a (99m)Tc-labeled Hynic-Annexin V derivative has been described and successfully evaluated in animal models of apoptosis. Prior to a phase I human study, the preparation of (99m)Tc-Hynic-Annexin V has been optimized. The influence of the Hynic-load of Annexin V, amount of protein, nature and amount of reducing agent, activity and co-ligand on the labeling yield were evaluated using ITLC and size-exclusion FPLC. Optimal labeling yields were obtained when 60-90 microgram Hynic-Annexin V was labeled with up to 1.11 GBq (30 mCi) (99m)TcO(4)-using 10-20 microgram SnCl(2).2H(2)O as reducing agent and 1.5 mg tricine as the co-ligand. Biodistribution in normal mice was comparable to literature data.

Publication types

  • Comparative Study
  • Evaluation Study
  • Validation Study

MeSH terms

  • Animals
  • Annexin A5 / chemical synthesis*
  • Annexin A5 / chemistry
  • Annexin A5 / pharmacokinetics*
  • Chromatography
  • Drug Design
  • Drug Stability
  • Humans
  • Isotope Labeling / methods*
  • Metabolic Clearance Rate
  • Mice
  • Organ Specificity
  • Organotechnetium Compounds / chemical synthesis*
  • Organotechnetium Compounds / chemistry
  • Organotechnetium Compounds / pharmacokinetics*
  • Quality Control
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Annexin A5
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium Tc 99m HYNIC annexin V