Optimization of the preparation of 99mTc-labeled Hynic-derivatized Annexin V for human use.
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.
D000818:Animals; D017304:Annexin A5 / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D002845:Chromatography; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C117287:technetium Tc 99m HYNIC annexin V