The study investigated routinely used radiopharmaceuticals containing lutetium-177 (177Lu), providing reference values for their effective half-life (T1/2,eff). So far, no guidelines regarding discharging this patients exist, are essential to ensure radiation protection of the public. This study contributes to the development of binding discharge criteria regarding 177Lu therapies. This retrospective multicenter study comprised eight nuclear medicine departments. Two commercially available products and two in-house preparations were considered. Radiation measurement methods, in terms of measuring device, setup, and time points were reported, as well as dose rate measurements for T1/2,eff calculation. The study includes 210 dose rate measurement sets with a mean administered activity of (7149 ± 522) MBq. When only measurements up to 48 h p.i. were taken into account the T1/2, eff were shorter (Pluvicto 1.30 d, Lutathera 1.40 d, ihPSMA 1.45 d, ihRRT 1.97 d) compared to 168 h (1.60 d, 1.89 d, 2.10 d, and 2.85 d, respectively). Differences were statistically significant for all compounds except Lutathera. The 90th percentile of the T1/2,eff observed in late measurements (Pluvicto 2.0 d, Lutathera 3.0 d, ihPSMA 3.5 d, ihRRT 4.0 d) can be considered conservative values for discharge calculations. The T1/2,eff of 177Lu is considerably shorter than its T1/2,phy, owing to the pharmacokinetics of the entire molecule. This highlights the need of considering biological clearance mechanisms into calculations of discharge times for patients treated with 177Lu. If direct measurements are not feasible in clinical routine, reference values support inpatient planning while ensuring radiation protection.

203/212Pb is a promising theranostic isotope pair for targeted alpha therapy (TAT) of neuroendocrine tumors (NET). VMT-α-NET is a novel SSTR2 targeting peptide that can be labeled with both isotopes. The aim of this work was to perform first clinical investigations of [203/212Pb]Pb-VMT-α-NET regarding imaging, biokinetics, tolerability and response. 12 patients (9 m/3 w; mean age 71, range 60–84) with progressive metastatic GEP-NET grade 1–3 received diagnostic imaging with [203Pb]Pb-VMT-α-NET (4.9 MBq/kg bw) up to 24 h p.i. (whole body SPECT/CT) and, if eligible, a single dose of [212Pb]Pb-VMT-α-NET therapy (1.2 MBq/kg bw) after exhaustion of all current therapies (including [177Lu]Lu- [225Ac]Ac-DOTATATE), and post-treatment imaging with [212Pb]Pb-VMT-α-NET up to 24 h p.i. (whole body SPECT/CT). Clinical and laboratory parameters were monitored. A visual and quantitative comparison was made with [68 Ga]Ga-DOTATATE PET scans before and 3 months after therapy. No high-grade adverse effects were observed in all patients evaluated with [203Pb]Pb-VMT-α-NET. All patients showed an initial high, but lesion-dependent heterogeneous intratumoral accumulation, comparable to [68 Ga]Ga-DOTATATE PET. Treatment with [212Pb]Pb-VMT-α-NET was also well tolerated by all patients without high-grade or serious adverse side effects. Post-therapeutic PET scans and tumor marker controls showed stable findings in all patients up to 3 months after treatment. Imaging with [203Pb]Pb-VMT-α-NET followed by a single dose of [212Pb]Pb-VMT-α-NET appears to be well tolerated with promising efficacy, even in a heterogenous and heavily pretreated patient population. Further studies are warranted to examine tolerability and efficacy over multiple treatment cycles in larger patient populations.

(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.

Background 203 Pb and 212 Pb show promise as theragnostic agents for targeted alpha therapy (TAT) because two chemically identical isotopes can be used for diagnostic imaging and treatment. In the 212 Pb decay chain, in addition to alpha and beta particles, a large number of photons are emitted, those with an energy of 239 keV and the characteristic X-rays of 212 Pb could be used for imaging. 203 Pb decays by photon emission with an energy of 279 keV, which appears suitable for gamma camera imaging. The aim of this study was to investigate suitable imaging protocols and to characterize the scintigraphic imaging properties and their implications for the clinical feasibility as theragnostic isotopes. Methods Planar and SPECT/CT images were obtained with medium- and high-energy collimators on a Siemens Symbia Intevo 6 using a NEMA image quality phantom in various phantom setups and another body-shaped phantom with several inserts. Different energy windows were investigated and measurements were evaluated in terms of sensitivity, count rate performance, spatial resolution, contrast recovery, lesion detectability, and image quantification. Results Evaluation of image quality showed superior imaging characteristics for 203 Pb compared to 212 Pb regarding spatial resolution, contrast recovery, image noise, and quantification accuracy. Both medium- and high- energy collimators were suitable for 203 Pb imaging, with the medium energy collimators showed slightly better imaging properties. Images obtained with the HE collimators in the 79 keV energy window showed the best visual image quality for 212 Pb. Due to high-energy photon emissions from 212 Pb daughter nuclides (e.g., 2.6 MeV from 208 Tl), dead time related count losses occurred even at low activities (20% count loss at 20 MBq for MELP collimators). Conclusions According to our results and first-in-human imaging studies, SPECT/CT imaging with the 203/212 Pb theragnostic pair is clinically feasible. 203 Pb is an appropriate imaging surrogate to investigate pharmacokinetics and perform predictive dosimetry. The less favorable imaging characteristics of 212 Pb make image quantification and post-treatment dosimetry challenging and require further research.

(1) Background: Targeted alpha therapy is an emerging field in nuclear medicine driven by two advantages: overcoming resistance in cancer-suffering patients to beta therapies and the practical application of lower activities of 212Pb- and 225Ac-labelled peptides to achieve the same doses compared to beta therapy due to the highly cytotoxic nature of alpha particles. However, quality control of the 212Pb/225Ac-radiopharmaceuticals remains a challenge due to the low activity levels used for therapy (100 kBq/kg) and the formation of several free daughter nuclides immediately after the formulation of patient doses; (2) Methods: The routine alpha detection on thin-layer chromatograms (TLC) of 212Pb- and 225Ac-labelled peptides using a MiniScanPRO+ scanner combined with an alpha detector head was compared with detection using an AR-2000 scanner equipped with an open proportional counter tube. Measurement time, resolution and validity were compared for both scanners; (3) Results: For 225Ac, the quality control values of the radiochemical purity (RCP) were within the acceptance criteria 2 h after TLC development, regardless of when the TLC probe was taken. That is, if the TLC probe was taken 24 h after radiosynthesis, the true value of the RCP was not measured until 5 h after TLC development. For 212Pb-labelled peptides, the probe sampling did not have a high impact on the value of the RCP for the MiniScanPRO+ and AR-2000. A difference was observed when measuring TLC with the AR-2000 in different modes; (4) Conclusions: The MiniScanPRO+ is fast, does not require additional equipment and can also measure the gamma spectrum, which may be important for some radiopharmaceutical production sites and regulatory authorities. The AR-2000 has a better signal-to-noise ratio, and this eliminates the need for additional waiting time after TLC development.

Zusammenfassung Ziel Gema ss den Anforderungen des Strahlenschutzrechts hat vor der erstmaligen Behandlung mit radioaktiven Stoffen eine Risikoanalyse (RA) zu erfolgen. Die Durchfuhrung einer solchen RA im Bereich der universitaren Nuklearmedizin wurde 2020 publiziert 1 . Entsprechend den gesetzlichen Bestimmungen hat eine Aktualisierung bei wesentlichen Anderungen von Teilprozessen zu erfolgen. Spatestens nach 3 Jahren wird eine uberprufung empfohlen. Die Umsetzung und die Ergebnisse der Aktualisierung werden vorgestellt. Methodik Es erfolgten schrittweise eine Evaluation der im Rahmen der initialen RA abgeleiteten Ma ss nahmen, eine Analyse eigener meldepflichtiger Vorkommnisse sowie von Vorkommnissen des BfS-gefuhrten Melde- und Informationssystems fur bedeutsame Vorkommnisse bei Strahlenanwendungen am Menschen (BeVoMed). Des Weiteren wurde die RA auf neue Therapien ausgeweitet und Teilbewertungen basierend auf aktuellen Erkenntnissen aktualisiert. Ergebnisse Die im Rahmen der 2019 durchgefuhrten RA identifizierten Ma ss nahmen fuhrten fur die Radiojodtherapie, die RSO sowie die SIRT zu einer Reduktion der Risikoprioritatszahlen aufgrund einer Erhohung der Entdeckungswahrscheinlichkeiten. Ein meldepflichtiges Vorkommnis wurde erkannt und analysiert. Die 3-jahrige Erfahrung fuhrte zudem bei vielen Prozessen zu einer Reduktion der Auftretenswahrscheinlichkeit. Schlussfolgerung Die Aktualisierung der RA hat zu einer Reduktion der Risikoprioritatszahl als Ma ss fur die Risikobewertung gefuhrt, was die hohe Sicherheit bei der Durchfuhrung nuklearmedizinischer Therapien unterstreicht. Dieses Resultat spiegelt sich in der geringen Anzahl gemeldeter nuklearmedizinischer Vorkommnisse des zentralen BeVoMed-Systems wider.

Somatostatin type 2 receptor (SSTR2) radionuclide therapy using beta - particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [177Lu]Lu-DOTA-TATE, 177 Lu]Lu-DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionuclides. Consequently, this study evaluates the pharmacokinetic effects of the albumin-binding domain cLAB4 on theranostic performance of copper-67-labeled NODAGA-TATE variants in an SSTR2-positive mouse pheochromocytoma (MPC) model. Methods: Binding, uptake, and release of radioligands as well as growth-inhibiting effects were characterized in cells grown as monolayers and spheroids. Tissue pharmacokinetics, absorbed tumor doses, and projected human organ doses were determined from quantitative SPECT imaging in a subcutaneous tumor allograft mouse model. Treatment effects on tumor growth, leukocyte numbers, and renal albumin excretion were assessed. Results: Both copper-64- and copper-67-labeled versions of NODAGA-TATE and NODAGA-cLAB4-TATE showed similar SSTR2 binding affinity, but faster release from tumor cells compared to the clinical reference [177Lu]Lu-DOTA-TATE. 177 Lu]Lu-DOTA-TATE. The bifunctional SSTR2/albumin-binding radioligand [67Cu]Cu-NODAGA-cLAB4- 67 Cu]Cu-NODAGA-cLAB4- TATE showed both an improved uptake and prolonged residence time in tumors resulting in equivalent treatment efficacy to [177Lu]Lu-DOTA-TATE. 177 Lu]Lu-DOTA-TATE. Absorbed doses were well tolerated in terms of leukocyte counts and kidney function. Conclusion: This preclinical study demonstrates therapeutic efficacy of [67Cu]Cu-NODAGA-cLAB4-TATE 67 Cu]Cu-NODAGA-cLAB4-TATE in SSTR2-positive tumors. As an intrinsic radionuclide theranostic agent, the radioligand provides stable radiocopper complexes and high sensitivity in SPECT imaging for prospective determination and monitoring of therapeutic doses in vivo. . Beyond that, copper-64- and copper-61-labeled versions offer possibilities for pre- and post-therapeutic PET. Therefore, NODAGA-cLAB4-TATE has the potential to advance clinical use of radiocopper in SSTR2-targeted cancer theranostics.

Abstract Background The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. Methods Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. Results The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. Conclusions Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose–response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Abstract Background In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter 225Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with 225Ac is still open, and 133La features attractive radiation properties to claim this place. However, in order to enable its translation into clinical use, upscaling of the production of this PET radionuclide is needed. Results A study on optimal irradiation parameters, separation conditions and an exhaustive product characterization was carried out. In this framework, a proton irradiation of 2 h, 60 µA and 18.7 MeV produced 133La activities of up to 10.7 GBq at end of bombardment. In addition, the performance of four different chromatographic resins were tested and two optimized purification methods presented, taking approximately 20 min with a 133La recovery efficiencies of over 98%, decay corrected. High radionuclide purity and apparent molar activity was proved, of over 99.5% and 120 GBq/µmol, respectively, at end of purification. Furthermore, quantitative complexation of PSMA-617 and mcp-M-PSMA were obtained with molar activities up to 80 GBq/µmol. In addition, both 133La-radioconjugates offered high stability in serum, of over (98.5 ± 0.3)% and (99.20 ± 0.08)%, respectively, for up to 24 h. A first dosimetry estimation was also performed and it was calculated that an 133La application for imaging with between 350 and 750 MBq would only have an effective dose of 2.1–4.4 mSv, which is comparable to that of 18F and 68Ga based radiopharmaceuticals. Conclusions In this article we present an overarching study on 133La production, from the radiation parameters optimization to a clinical dose estimation. Lanthanum-133 activities in the GBq range could be produced, formulated as [133La]LaCl3 with high quality regarding radiolabeling and radionuclide purity. We believe that increasing the 133La availability will further promote the development of radiopharmaceuticals based on macropa or other chelators suitable for 225Ac. Graphical abstract

After transarterial radioembolization (TARE) with microspheres loaded with holmium-166, radioactivity is excreted from the body. The aim of this study was to evaluate radioactive renal and intestinal excretions after TARE planning and treatment procedures with holmium-166-loaded microspheres and to correlate the findings with the intratherapeutic effective half-life. Urinary and intestinal excretions of patients who underwent TARE procedures were collected during postinterventional intervals of 24 h (TARE planning) and 48 h (TARE treatment). Whole-body effective half-life measurements were performed. Calibrations of the 166Ho measuring system showed evidence of long-living nuclides. For excretion determination, 22 TARE planning procedures and 29 TARE treatment procedures were evaluated. Mean/maximum total excretion proportions of the injected 166Ho were 0.0038%/0.0096% for TARE planning procedures and 0.0061%/0.0184% for TARE treatment procedures. The mean renal fractions of all measured excretions were 97.1% and 98.1%, respectively. Weak correlations were apparent between the injected and excreted activities (R2 planning/treatment: 0.11/0.32). Mean effective 166Ho half-lives of 24.03 h (planning) and 25.62 h (treatment) confirmed low excretions. Radioactive waste disposal regulations of selected jurisdictions can be met but must be reviewed before implementing this method into clinical practice. Inherent long-living nuclide impurities should be considered.

Ziel/Aim Alpha-Strahler rücken zunehmend in den Fokus der nuklearmedizinischen Therapie. Neben Ra-223 und Ac-225 erscheint Pb-212 (HWZ: 10,6 h) als vielversprechendes Isotop, vor allem aufgrund der Eignung als Theranostik-Nuklid in Kombination mit dem Gammastrahler Pb-203. Innerhalb der Zerfallskette über Bi-212, Po-212 und Tl-208 werden ein α-Teilchen mit Energien zwischen 5,6 und 8,8 MeV emittiert. Begleitet wird die Zerfallskette jedoch durch eine Vielzahl emittierter Gammaquanten, wovon vor allem jene des Tl-208 mit einer Energie von 2,6 MeV besondere Strahlenschutzbeachtung erfordern.

Ziel/Aim This study aimed to investigate the urinary and intestinal excretion of Ho-166 in the first 24h after Ho-166-workup resp. 48h after Ho-166-treatment while observing the intratherapeutic effective half-life.

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for αvβ3 integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation. Furthermore, the therapeutic properties of the [198Au]AuNPs were evaluated in vitro on U87MG cells in terms of cell survival, suggesting that these [198Au]AuNPs are a useful basis for future therapeutic concepts.

with dosimetric Lu-satoreotide tetraxetan (Lu-DOTA-JR11) SPECT/CT in patients with metastatic neuroendocrine tumors undergoing peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2020;47:3047–3057. 3. Mansi R, Fani M. Design and development of the theranostic pair LuOPS201/Ga-OPS202 for targeting somatostatin receptor expressing tumors. J Labelled Comp Radiopharm. 2019;62:635–645. 4. Weber WA, Barthel H, Bengel F, Eiber M, Herrmann K, Sch€afers M. What is theranostics? J Nucl Med. 2023;64:669–670.

Ziel/Aim Gemäß der Leitlinie der DGN ist nach Radioiodtherapie eine posttherapeutische Dosisbestimmung erforderlich. Üblicherweise erfolgt diese anhand von Messungen an einem Sondenmessplatz. Aus diesen Messungen können die effektive Halbwertszeit und der Radioiod-Uptake abgeschätzt werden. Dieses Vorgehen ist mit einer erhöhten Variabilität und Unsicherheit behaftet. Mittels SPECT/CT-Aufnahmen sollte eine 3D-Dosisverteilung in der Schilddrüse ermittelt und das Verfahren der Dosimetrie optimiert werden.