Synthesis, pharmacokinetics, and biodistribution of 67GA deferoxamineacetyl-cysteinylbiotin

The exceptionally high affinity of streptavidin for biotin may be exploited for two-step in vivo approaches for delivering radiolabelled biotin derivatives to lesion-bound streptavidin-conjugated monoclonal antibodies. A radiolabeled biotin derivative was prepared, and its characterization, stability, pharmacokinetics, and biodistribution studies are presented. This derivative contains deferoxamine, a chelating moiety with high affinity for trivalent metals suitable for imaging and therapy. Deferoxamineacetyl-cysteinylbiotin (DACB) was synthesized in three steps: nucleophilic reaction of deferoxamine with N-hydroxysuccinimide iodoacetate, aminolysis of N-hydroxysuccinimide biotin by L-cysteine, followed by coupling of cysteinylbiotin with N-iodoacetyldeferoxamine. DACB was characterized by matrix-assisted laser desorption/ionization MS. Radiolabeling of DACB with 67Ga led to a labeling efficiency of > 95%. Pharmacokinetics of 67Ga DACB exhibited rapid blood clearance, with < 10% circulating at 30 min and < 1% at 6 hr. Plasma samples collected at various time intervals showed > 95% binding with streptavidin, indicating in vivo stability of 67Ga DACB. Urinalysis showed > 80% of the administered dose excreted at 6 hr. Biodistribution data at 6 hr showed < 1% radioactivity remaining per organ.