Novel 68Ge/68Ga generator system using polysaccharide polymers containing N-methylglucamine groups as adsorbents for 68Ge

103 Objectives We have previously elucidated organic polymers (PGMA-EG) containing N-methylglucamine (MG) groups as useful adsorbents for a 68Ge/68Ga generator using neutral eluent. Introduction of carboxyl groups near the MG groups of the PGMA-EG increased elution rate of 68Ga, indicating that hydrophilic environments close to MG may be important for elution efficiency of 68Ga. In this study, we developed new adsorbents for 68Ge by introducing MG groups into Sephadex series as hydrophilic polymer matrix. Methods Sephadex-type adsorbents (Sepha-MGs) were prepared from Sephadex series (G-10~G-75) by epoxidation with epichlorohydrin, followed by nucleophilic addition of epoxy groups with MG. Using a batch method, the adsorption characteristics of the Sepha-MGs for Ge (IV) and 68Ge were investigated. Sepha-MGs were packed into columns, and 68Ge solution adjusted at pH 7 was passed through the column. The 68Ga produced on Sepha-MGs was eluted by using 0.1 M trisodium citrate. PET imaging of U87MG-inoculated tumor bearing mice was performed using integrin-targeted 68Ga-c(RGDyK)-SCN-Bz-NOTA. Results In a batch method, 68Ge was rapidly adsorbed onto the Sepha-MG series. Sepha(15)-MG and Sepha(25)-MG had high MG content and adsorption capacity of Ge. 68Ge (3.7 MBq) was effectively adsorbed on the Sepha-MG packed columns, and about 80 % of the 68Ga was eluted by 1.0 mL of 0.1 M trisodium citrate. When using much higher activity of 68Ge (74 MBq), 70-80% of the 68Ga in the column was eluted in 1 mL of the eluate and the leakage of 68Ge was less than 0.001 %. 68Ga-c(RGDyK)-SCN-Bz-NOTA (15−17 MBq) was prepared from the generator-produced 68Ga-citrate in yields of 85−92%. In PET studies, tumor tissue in the mice was clearly visualized using 68Ga-c(RGDyK)-SCN-Bz-NOTA, in which the uptake was drastically decreased by c(RGDyK) (10 mg/kg). Conclusions This study suggested that Sepha-MG series are useful adsorbents for 68Ge/68Ga generator systems. Research Support This study was supported in part by a Special Funds for Education and Research (System to produce PET radiopharmaceuticals without cyclotron) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.