The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress. A particular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g., for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes as well as their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.

This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.

(1) Background: As the demand for ²¹²Pb for clinical theranostics rises, empirical studies that examine the radiation safety implications of different ²²⁴Ra sources are needed to facilitate discussions with local authorities for the translation of ^203/212Pb theranostics routine clinical practice. (2) Methods: Environmental ²²⁰Rn (Thoron) emanation was detected by a RAD7 detector in the vicinity of respective ²¹²Pb sources and additional alpha-dosimeters to detect ²²⁰Rn during generator elution, radiosynthesis, and quality control. Personnel gamma exposure was measured using whole-body and ring dosimeters. Generators included those based on wet-chemical-process- and emanation-based technology. (3) Results: During generator handling, varying levels of ²²⁰Rn were observed in the vicinity of generators. An additional monthly whole-body dose must be considered when handling different sources of ²¹²Pb generators, and this depends upon local shielding and the handling approaches toward use of the technology. (4) Conclusions: ²²⁴Ra in any form (including radionuclide generators) should always be handled within a fume hood to keep potential contamination and exposure to personnel as low as reasonably achievable. Following standard practices of radiation safety, generators of ²¹²Pb can be used safely for theranostic applications.