Gallium-68 labeling of albumin and albumin microspheres

Because of the high stability constant of gallium transferrin, the formation of a protein that will be stable in vivo and labeled with gallium-68 (a positron emitter) requires preliminary coupling of a strong chelating group to the protein. In the present study, we have used a reaction developed by Krejcarek and Tucker, in which DTPA is coupled to proteins by the formation of an amide bond. Using human serum albumin (HSA) as a model, we have studied the efficiency of the reaction of HSA with the mixed acid anhydride of the quarternary triethyl ammonium salt of DTPA and butyl formate, as a function of the ratio of albumin to DTPA. After purification of the DTPA-labeled HSA, it is possible to prepare Ga-68-labeled albumin in high yield by chelation of the Ga-68 with the DTPA-labeled protein. In vitro and in vivo stability studies showed that the labeled protein was stable over a period of several hours. The same type of bifunctional chelate has been used to attach Ga-68 to HSA microspheres.