SYNTHESIS, PHARMACOKINETICS, AND BIODISTRIBUTION OF GA-67 DEFEROXAMINEACETYL-CYSTEINYLBIOTIN

The exceptionally high affinity of streptavidin for biotin may be expl oited for two-step in vivo approaches for delivering radiolabeled biot in derivatives to lesion-bound streptavidin-conjugated monoclonal anti bodies. A radiolabeled biotin derivative was prepared, and its charact erization, stability, pharmacokinetics, and biodistribution studies ar e presented, This derivative contains deferoxamine, a chelating moiety with high affinity for trivalent metals suitable for imaging and ther apy, Deferoxamineacetyl-cysteinylbiotin (DACB) was synthesized in thre e steps: nucleophilic reaction of deferoxamine with N-hydroxysuccinimi de iodoacetate, aminolysis of N-hydroxysuccinimide biotin by L-cystein e, followed by coupling of cysteinylbiotin with N-iodoacetyldeferoxami ne. DACB was characterized by matrix-assisted laser desorption/ionizat ion MS, Radiolabeling of DACB with Ga-67 led to a labeling efficiency of > 95%, Pharmacokinetics of Ga-67 DACB exhibited rapid blood clearan ce, with < 10% circulating at 30 min and < 1% at 6 hr, Plasma samples collected at various time intervals showed > 95% binding with streptav idin, indicating in vivo stability of Ga-67 DACB, Urinalysis showed > 80% of the administered dose excreted at 6 hr, Biodistribution data at 6 hr showed < 1% radioactivity remaining per organ.