Development of a 68Ge/68Ga Generator System Using Polysaccharide Polymers and Its Application in PET Imaging of Tropical Infectious Diseases

ABSTRACT
Gallium-68 (⁶⁸Ga) is a positron emitter for clinical positron emission tomography (PET) applications that can be produced by a ⁶⁸Ge/⁶⁸Ga generator without cyclotron. However, commercially available ⁶⁸Ge/⁶⁸Ga generator systems require multiple steps for the preparation of ⁶⁸Ga radiopharmaceuticals and are sometimes plagued by metallic impurities in the ⁶⁸Ga eluent. We developed a ⁶⁸Ge/⁶⁸Ga generator system using polysaccharide-based adsorbents and direct application of the generatoreluted ⁶⁸Ga-citrate to PET imaging of tropical infectious diseases. NMethylglucamine
(MG) as a 68Ge-adsorbing unit (Sepha-MGs) was introduced to a series of Sephadex G-10, G-15, G-25, G-50, and G-75. In
the batch method, over 97% of the ⁶⁸Ge in the solution was adsorbed onto the Sepha-MG series within 15 min. In particular, ⁶⁸Ge was effectively adsorbed on the Sepha(15)-MG packed columns and 70−80% of the ⁶⁸Ga was eluted by 1 mL of 0.1 M trisodium citrate with low ⁶⁸Ge contamination (<0.001%). The chemical form of the generatoreluted ⁶⁸Ga solution was identified as ⁶⁸Ga-citrate. In PET studies, affected regions in mice infected with Leishmania and severe fever with thrombocytopenia syndrome virus were clearly visualized using the ⁶⁸Ga-citrate. Sepha-MGs are useful adsorbents for ⁶⁸Ge/⁶⁸Ga generator systems with high ⁶⁸Ga elution efficiency and minimal ⁶⁸Ge breakthrough. These results indicated that eluted ⁶⁸Ga-citrate can be directly used for PET imaging of infectious sites in mice. This novel generator system may be useful for straightforward PET imaging of infection in clinical practice.