Detailed evaluation of different ⁶⁸Ge/⁶⁸Ga generators: an attempt toward achieving efficient ⁶⁸Ga radiopharmacy

Abstract

The present study is aimed at carrying out a comparative performance evaluation of different types of (68)Ge/(68)Ga generators to identify the best choice for use in (68)Ga-radiopharmacy. Over the 1 year period of evaluation, the elution yields from the CeO2-based and SiO2-based (68)Ge/(68) Ga generators remained almost consistent, in contrast to the sharp decrease observed in the elution yields from TiO2 and SnO2-based generators. The level of (68)Ge impurity in (68)Ga eluates from the CeO2 and SiO2-based (68)Ge/(68)Ga generator was always <10(-3)%, while this level increased from 10(-3)% to 10(-1)% in case of TiO2 and SnO2-based generators. The level of chemical impurities in (68)Ga eluates from CeO2 and SiO2-based (68)Ge/(68)Ga generators was negligibly low (<0.1 ppm) in contrast to the significantly higher level (1-20 ppm) of such impurities in eluates from other two generators. As demonstrated by radiolabeling studies carried out using DOTA-coupled dimeric cyclic RGD peptide derivative (DOTA-RGD2), CeO2-PAN and SiO2-based generators are directly amenable for radiopharmaceutical preparation, whereas the other generators can be only used after post-elution purification of (68)Ga eluates. Clinically relevant dose of (68)Ga-DOTA-RGD2 was prepared in a hospital radiopharmacy for non-invasive visualization of tumors in breast cancer patients using positron emission tomography.

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

“…Several metallic impurities have been found in the commercially available generators. 13 We have not examined the metal impurity of Sepha-MGs, but the organic polymers might not contain any intrinsic metal. The 68 Ge breakthrough from the Sepha(MG)-15-based generator was less than 0.001%, which is comparable to that from the clinically available generators (Table 2).…”

“…11,12 All of these generators require HCl solution to elute the 68 Ga, thereby necessitating multiple synthetic and purification steps for the production of 68 Ga radiopharmaceuticals. 13 It would be ideal if the generator-eluted 68 Ga solution could directly be used as a radiopharmaceutical similarly to 99 Mo/ 99m Tc.…”

Initial clinical experience with 68Ga-DOTA-NOC prepared using 68Ga from nanoceria-polyacrylonitrile composite sorbent-based 68Ge/68Ga generator and freeze-dried DOTA-NOC kits

“…A detailed performance evaluation of both these generators was recently carried out by our group, and the performances of these two generators were found to be comparable. [20] Thus, we could ensure that our indigenously developed generator is suitable for clinical use.…”

A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb

“…68 Ge reaction by irradiating nat Ga with 23 MeV proton energy [89]. The 68 Ge (T 1/2 = 270.95 d) produced is separated from the Ga target material [105,106] and the final product loaded onto an inorganic substrate (SnO 2 or TiO 2 ) which is shielded with Pb. 68 Ge decays by electron capture to 68 Ga (T 1/2 = 67.71 min) and the daughter is subsequently eluted from the resin using dilute HCl (0.1 -0.6 M HCl) which is introduced to a GMP module for radiolabeling.…”