Evaluation of the 177mLu-concentration in in-house produced 177Lu-radiopharmaceuticals and commercially available Lutathera®.

BACKGROUND: 177Lu-radiopharmaceuticals can contain the metastable impurity [177mLu]lutetium with a physical half-life of 160.4 days, in varying concentrations depending on the route of production of the radionuclidic precursor [177Lu]lutetium. Due to the long half-life of [177mLu]lutetium, difficulties with waste disposal or sterility testing could arise. Here, we analyzed several 177Lu-samples of different origins and suppliers regarding their 177mLu-concentration. RESULTS: All samples tested showed a 177mLu-concentration in the range that was stated on the certificate of analysis from the supplier which is in accordance with the European Pharmacopoeia. CONCLUSIONS: Although all 177mLu-concentrations were in accordance with the European Pharmacopoeia, we need to take into account the respective national legislation regarding radioactivity release limits. With regard to the German legislation, several probes for sterility testing in external laboratories could not be released for transport due to the concentration of [177mLu]lutetium. Moreover, waste water tanks should specifically be monitored for 177mLu-concentration, when e.g. Lutathera® is administered in the clinic.

Optimization of 177Lu-labelling of DOTA-TOC, PSMA-I&T and FAPI-46 for clinical application.

BACKGROUND: 177Lu-radiopharmaceuticals are routinely used for the treatment of various tumor entities. The productions of radiopharmaceuticals follow strict good-manufacturing practice guidelines and synthesis optimizations thereof have a strong impact on e.g. the quality of the product, radiation safety and costs. The purpose of this study is to optimize the precursor load of three radiopharmaceuticals. For that, different precursor loads were evaluated and compared to previously reported findings. RESULTS: All three radiopharmaceuticals were successfully synthesized in high radiochemical purities and yields on the ML Eazy. The precursor load was optimized for [177Lu]Lu-FAPI-46 from 27.0 to 9.7 µg/GBq, for [177Lu]Lu-DOTATOC from 11 to 10 µg/GBq and for [177Lu]Lu-PSMA-I&T from 16.3 to 11.6 µg/GBq. CONCLUSIONS: We successfully reduced the precursor load for all three radiopharmaceuticals while maintaining their quality.

Fully-automated production of [68Ga]Ga-FAPI-46 for clinical application.

BACKGROUND: [68Ga]Ga-FAPI-46 is a promising radiopharmaceutical for in vivo detection of the fibroblast activation protein by positron emission tomography. Until now, the synthesis of [68Ga]Ga-FAPI-46 has been only performed manually. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on two different commercially available synthesis modules in order to make the tracer readily available for clinical application. RESULTS: The synthesis of [68Ga]Ga-FAPI-46 with different amounts of precursor (10-50 µg) on the Modular Lab PharmTracer (MLPT) and Modular Lab eazy (ML eazy) from Eckert & Ziegler with a customized synthesis template and a customized single-use cassette yielded best results with 50 µg FAPI-46 for clinical multi-dose application. All relevant quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia. CONCLUSIONS: [68Ga]Ga-FAPI-46 was successfully synthesized fully-automated on the synthesis modules Modular Lab PharmTracer and ML eazy and is, thus, available for multi-dose application in clinical settings.

Krylov-space approach to the equilibrium and nonequilibrium single-particle Green's function.

The zero-temperature single-particle Green's function of correlated fermion models with moderately large Hilbert-space dimensions can be calculated by means of Krylov-space techniques. The conventional Lanczos approach consists of finding the ground state in a first step, followed by an approximation for the resolvent of the Hamiltonian in a second step. We analyze the character of this approximation and discuss a numerically exact variant of the Lanczos method which is formulated in the time domain. This method is extended to obtain the nonequilibrium single-particle Green's function defined on the Keldysh-Matsubara contour in the complex time plane which describes the system's nonperturbative response to a sudden parameter switch in the Hamiltonian. The proposed method will be important as an exact-diagonalization solver in the context of self-consistent or variational cluster-embedding schemes. For the recently developed nonequilibrium cluster-perturbation theory, we discuss its efficient implementation and demonstrate the feasibility of the Krylov-based solver. The dissipation of a strong local magnetic excitation into a non-interacting bath is considered as an example for applications.