[en] A two-compartment ²¹²Pb generator has been constructed and characterized physically and chemically. It is based on transport by airflow of gaseous ²²⁰Rn emanating from thin layers of [²²⁸Th]barium stearate. ²²⁰Rn is collected in a glass bubbler by extraction into an organic solvent and solidified at temperatures below -72 deg. C. Tracer studies show that the decay product ²¹²Pb can be recovered with approximately 70% yield. It is suggested that this generator design could accommodate therapeutic levels of ²¹²Pb/²²⁸Th

[en] A HPLC system has been developed for carrier free and rapid delivery in a physiological buffer of the α-particle emitting bone-seeking radiopharmaceutical ²¹²Bi-DOTMP. ²⁰⁵Bi-DOTMP was synthesized and HPLC purified to mimic and visualize the deposition pattern in bony tissues of ²¹²Bi-DOTMP by autoradiography. Inhomogeneous bone deposits were found with the highest concentration in the bone matrix, the endosteum and in the growth zones of young mice. Analysis of urine samples showed that ²⁰⁵Bi-DOTMP was cleared as an intact complex

[en] PSMA (Prostate-Specific Membrane Antigen) is a transmembrane protein which is overexpressed in most cases of prostate cancer. Expression level of this protein has a strong correlation to the stage of the disease, which makes PSMA a very attractive target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). One of the most promising radioligands for the treatment of mCRPC is a small-molecule-based PSMA-617 equipped with a DOTA chelator. PSMA-617 labelled with ¹⁷⁷Lu has been successfully applied in clinics. A recently introduced ¹⁶¹Tb has similar chemical and nuclear characteristics to ¹⁷⁷Lu, but also emits substantial amount of low-energy conversion and Auger electrons, which is believed to enhance therapeutic efficacy of the radiopharmaceutical. We optimized the reaction conditions for the labelling PSMA-617 with ¹⁶¹Tb and investigate the radiolytic stability of the labelled compound. Radiolabelling was achieved by adding [¹⁶¹Tb]TbCl³ (100-200 MBq) to the 1 mM water solution of PSMA-617 in acetate buffer (pH 4.5). Reaction mixture was stirred for 15-30 min at 95 °C. Radiochemical yield (98 %), as well as radiolytic stability, was studied by HPLC with radiometric detection. Reaction samples were measured every 24 hours. No stabilizing additives were used in this experiment. Promising ligand PSMA-617 was successfully labelled with ¹⁶¹Tb. Radiolytic decomposition of the radiolabelled compound was apparent from the radiochromatograms. Further improvement of reaction conditions is warranted in order to suppress radiolytic processes.

[en] Terbium-161 can be prepared as no carrier added by neutron irradiation of highly enriched gadolinium-160 target in a nuclear reactor, through indirect production route ¹⁶⁰Gd (n,γ) ¹⁶¹Gd → ¹⁶¹Tb. After irradiation,terbium must be separated from the target, typically by using cation exchange chromatography. In this work, several irradiations of highly enriched ¹⁶⁰Gd target in the form of oxide or nitrate were performed in the nuclear reactor LVR 15. For separation of ¹⁶¹Tb from target, cation exchange chromatography (Dowex 50W×8 (H+), 100-200 mesh) with variously concentrated α-hydroxyisobutyric acid as eluent was used. The presence of ¹⁶¹Tb and possible radionuclide impurities was verified by gamma spectrometry on an HPGe detector. The fractions containing ¹⁶¹Tb were purified from α-hydroxyisobutyric acid also on the cation exchange resin, using hydrochloric acid as eluent. The presence of stable impurities was verified by ICP-MS method.

[en] A microdosimetry model was developed for the prediction of cell viability for irregular non-spherical cells that were irradiated by low energy, short range Auger electrons. Measured cell survival rates for LNCaP prostate cancer were compared to the computational results for the radioisotopes ¹⁷⁷Lu and ¹⁶¹Tb (conjugated to PSMA). The cell geometries used for the computations were derived directly from the cell culture images. A general computational approach was developed to handle arbitrary cell geometries, based on distance probability distribution functions (PDFs) derived from basic image processing. The radiation calculations were done per coarse grained PDF bin to reduce computation time, rather than on a pixel/voxel basis. The radiation dose point kernels over the full electron spectrum were derived using Monte Carlo simulations for energies below 50 eV to account for the propagation of Auger electrons over length scales at and below a cellular radius. The relative importance of short range Auger electrons were evaluated between the two nuclide types. The microdosimetry results were consistent with the cell viability measurements, and it was found that ¹⁶¹Tb was more efficient than ¹⁷⁷Lu primarily due to the short range Auger electrons. We foresee that imaging based microdosimetry can be used to evaluate the relative therapeutic effect between various nuclide candidates. (paper)