Simple, fast preparation of gallium-68-labelled human serum albumin microspheres

Abstract

Following a study of the main factors involved in the 68-Ga labelling of human serum albumin microspheres (H.S.A.M.), especially methods of production and preparation of active solution and conditions of radioelement fixation on the protein support, the practical details of a fast technique (60 min) based on the process described by Hnatowich are presented. This method gives high labelling yields (93 +/- 3%), and after washing of the microspheres leads to a radiopharmaceutical product almost without free 68Ga (less than 2%). The spheres ready for use carry a total radioactivity corresponding to about 35%, including decay, of the activity originally recovered in the generator eluate and to more than 98% of that, found in the final suspension. The labelled product is sterile, non-pyrogenic and non-toxic. When it is injected in animals by left ventrical catheterization the uptake rates in the heart, lungs, spleen, left kidney and right kidney are similar to those observed with reference 85Sr-labelled carbonized microspheres. This radiopharmaceutical, easy to prepare and having excellent biological and nuclear properties, seems ideally suited for the scanning of organs by position emission tomoscintigraphy.

99mTc-68Ga-ICG-Labelled Macroaggregates and Nanocolloids of Human Serum Albumin: Synthesis Procedures of a Trimodal Imaging Agent Using Commercial Kits

“…On the contrary, a trapping mechanism due to specific interactions of the Ga 3+ ions with protein lone pairs exposed at the particle surface cannot be excluded [11]. pH is an essential parameter influencing Ga binding to NC/MAA with an optimal range between 3.5 and 6.5 [3,[11][12][13] as confirmed by our results. In all likelihood, the protein structure does not favour the binding of the GaCl − 4 complex in strong acidic conditions.…”

“…Macroaggregate counts averaged about 2765000 MAA particle/vial, in conformity with the manufacturer's specifications (2-4 × 10 6 particles/vial). We started measuring the particle size of MAA commercial kits labelled with 68 Ga after 15 min incubation at 75°C, as reported in the literature [11][12][13][14]. However, optical microscopy revealed a substantial modification in MAA particle size and structure.…”

“…Several attempts have been made to label MAA commercially available kits with 68 Ga, which excluded technetium labelling [21] via chelation [22]. However, this approach was limited to pilot studies regarding albumin particles [12,13]. More recent research, including our own findings, indicates that an efficient 68 Ga labelling does not require preconjugation with DOTA or other chelators.…”

A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer

“…Albumin microsphere labeling with 68 Ga can be effectively achieved either by hydrolysis and precipitation of the 68 Ga 3+ ion in the presence of the albumin particles (Chester, et al, 1975;Hnatowich, 1976;Yvert, et al, 1979;Hayes, et al, 1981;Maziere, et al, 1986;Mintun, et al, 1986;Schuster and Green, 1987), or by covalent conjugation of the microspheres with a high-affinity gallium chelating ligand (Wagner and Welch, 1979). When the FDA-approved 99m Tc-human serum albumin microsphere product was withdrawn from the U.S. market, the 68 Ga-labeling method for albumin microspheres was adapted for use with the commercial kits available for the preparation of [ 99m Tc]Tc-MAA (macroaggregared human serum albumin) (Even and Green, 1989).…”