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

利用多糖聚合物开发(68)Ge/(68)Ga发生器系统及其在热带传染病PET成像中的应用

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Abstract

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

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