Otto: a 4.04\u2009GBq (109\u2009mCi) 68Ge/68Ga generator, first of its kind - extended quality control and performance evaluation in the clinical production of [68Ga]Ga-PSMA-11

Nicole N. Waterhouse,John W. Babich,Anastasia Nikolopoulou,Alejandro Amor-Coarasa

doi:10.1186/s41181-019-0087-y

Abstract

BackgroundHere we report on the comprehensive quality control of a 4.04 GBq (109 mCi) generator supplied by itG (Munich, Germany), and used for routine production of [68Ga]Ga-PSMA-11 for clinical imaging. The performance of the 4.04 GBq itG 68Ge/68Ga generator was studied for a year and parameters including elution yield, elution profile, radioactive and stable contaminants were collected. The production yields of a series of 175 [68Ga]Ga-PSMA-11 clinical batches are also reported herein.ResultsThis first-of-its-kind GMP grade 68Ge/68Ga generator from itG with a nominal activity of 4.04 GBq (109 mCi) showed a stable 68Ga elution profile with elution efficiency averaging 58.3 ± 3.7%. 68Ge contaminant in the eluent slightly increased over time but remained 100x lower than those reported for comparable 1.85 GBq (50 mCi) itG generators. Metal impurities were found in concentrations lower than 100 ng/ml (ppb) throughout the study. [68Ga]Ga-PSMA-11 was obtained in 89 ± 4% radiochemical yields and > 99% radiochemical and chemical purities.Conclusion4.04 GBq (109 mCi) itG 68Ge/68Ga generator is suitable for routinely produced 68Ga tracers used in the clinic. Up to 30% higher amount of final drug product was obtained as compared to the 1.85 GBq (50 mCi) itG generator, and as a result larger number of studies could be performed, while reducing the synthetic burden.

Highlights

The value of PSMA-targeted diagnosis and therapy monitoring of prostate cancer by means of PET/CT imaging is undeniable (Hana et al 2018)
While several groups are working on an 18F-labeled substitute for PSMA imaging (Kelly et al 2017; Giesel et al 2017; Szabo et al 2015), [68Ga]Ga-PSMA-11 (a.k.a. [68Ga]Ga-PSMA-HBED-CC or [68Ga]Ga-DKFZ-PSMA-11) is the current gold standard (Hana et al 2018)
The commercially available 68Ge/68Ga generators do not exceed the capacity of 1.85 GBq (50 mCi) (Amor-Coarasa et al 2016, 2017, 2018; McElvany et al 1984; Roesch 2013; Greene and Tucker 1961)

Summary

Introduction

The value of PSMA-targeted diagnosis and therapy monitoring of prostate cancer by means of PET/CT imaging is undeniable (Hana et al 2018). The commercially available 68Ge/68Ga generators do not exceed the capacity of 1.85 GBq (50 mCi) (Amor-Coarasa et al 2016, 2017, 2018; McElvany et al 1984; Roesch 2013; Greene and Tucker 1961). We report a comprehensive quality control of a 4.04 GBq (109 mCi) 68Ge/68Ga generator produced by Isotopen Technologies Garching GmbH (itG GmbH, Munich, Germany); lovingly and appropriately referred to as “Otto” (Fig. 1). We evaluate its use in the routine clinical production of [68Ga]Ga-PSMA-11 in combination with an iQS Fluidic Labeling Module. We report on the comprehensive quality control of a 4.04 GBq (109 mCi) generator supplied by itG (Munich, Germany), and used for routine production of [68Ga]Ga-PSMA-11 for clinical imaging. The production yields of a series of 175 [68Ga]Ga-PSMA-11 clinical batches are reported

Methods

Results

Discussion

Conclusion