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

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.