Holger Hartmann

Purpose: ^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. Methods: 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. Results: 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. Conclusion: 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.

According to the requirements of radiation protection legislation, patients may only be discharged from the nuclear medicine therapy ward if it is ensured that the cumulative radiation exposure of the population is below 1 mSv per year. In the present study, dose measurements of patients after radioiodine therapy (RIT) and their relatives are to be used to prove that the radiation exposure resulting from the medical application is low and that the legal framework conditions are complied with. Furthermore, the results allow conclusions to be drawn about the measurement accuracy of the dosimeters used. Methods: In 147 patients after RIT and their relatives, the dosage was measured over 14 days with different measuring systems. Finger ring dosimeters (FRD) were worn during the whole day, furthermore the dose was determined by non-official OSL and TLD dosimeters during the sleep phase. Results: 88 data sets were used for the final analysis. With the FRD, dose values between 0.1–50 mSv were determined for the patients. As expected, the finger ring dose of the relatives was significantly lower, averaging 0.75 mSv compared to 10 mSv for the patient. For the TLD and OSL used in the sleep phase, the measured values were in the same range. The reproducibility of the measurement results was significantly better for the OSL than for the TLD. Conclusion: Despite method-related measurement uncertainties, it can be concluded that the exposure dose of patients’ relatives after radioiodine therapy is low and that the legal requirements are met. Moreover, the now official OSL dosimeters represent a more accurate and for the chosen measurement task better suited measurement system than the TLD. Key Points: Citation Format Received: 06 February 2022 Accepted: 05 January 2023 Article published online: 09 May 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Radiomercury 197mHg and 197Hg, henceforth referred to as 197(m)Hg, is a promising theranostic radionuclide endowed with properties that allow diagnostic and therapeutic applications. The aim of this work was to investigate the capabilities of 197(m)Hg for nuclear medicine imaging. Therefore measurements were performed by using a Philips BrightView SPECT camera. Furthermore, Monte Carlo simulations using the GATE software were performed to theoretically explore the imaging contribution from the various gamma and X-ray emissions from 197(m)Hg for a commercial clinical camera with low-energy high-resolution (LEHR) and high-energy general-purpose (HEGP) collimators. We estimated the spatial resolution by using a four-quadrant bar phantom, and we evaluated the planar and tomographic images from an abdominal phantom containing three cylindrical sources of 197(m)Hg solution. A good accordance between measurements and simulations was found for planar and SPECT imaging. Simulations allowed the decomposition of the detected energy spectrum into photon origins. Measurements and simulations for the bar phantom revealed that for the LEHR collimator, the 6-mm pattern could be resolved, whereas for the HEGP collimator, the resolution is about 10 mm. Furthermore, we found that no significant image distortion results from high-energy photons when using the LEHR collimator. We demonstrated the imaging capabilities of 197(m)Hg which is essential both for diagnostic applications and to determine the in vivo biodistribution for dose calculations in therapeutic applications.

Purpose: ⁶⁸Ga-labelled compounds are increasingly used for somatostatin-receptor scintigraphy because of their favourable biokinetic properties, a higher tumour-to- background contrast and higher diagnostic accuracy compared to the gamma-emitting tracer ¹¹¹In-DTPA-octreotide. Recently, we have introduced the new tracer ⁶⁸Ga-DOTA- 3-iodo-Tyr³-Thr⁸-octreotide (⁶⁸Ga-HA-DOTA- TATE). The present study demonstrates the biodistribution and radiation dosimetry of this tracer in humans. Patients, methods: Seven men were enrolled in this analysis. Every patient underwent a 20 min dynamic PET scan after intravenous injection of about 114 ± 9 MBq of ⁶⁸Ga-HA-DOTATATE. This was followed by two whole-body scans at 30 min p. i. and 120 min p. i. Blood radioactivity concentration was determined non-invasively from a ROI drawn over the aorta. Urine was collected until the time of the last scan. Liver, spleen, kidneys and urinary bladder wall were included in the dosimetric estimation that was carried out with the software package OLINDA 1.0. Results: Physiological ⁶⁸Ga- HA-DOTATATE uptake was observed in the pituitary gland, thyroid, salivary glands, liver, spleen, kidneys, urinary bladder, adrenals and intestine. Organs with the highest absorbed dose were spleen (0.26 ± 0.11 mSv/MBq), kidneys (0.14 ± 0.03 mSv/MBq) and liver (0.12 ± 0.02 mSv/MBq).The estimated effective dose was 0.024 ± 0.001 mSv/MBq. Conclusion: Our study demonstrates biokinetics and radiation exposure of the ⁶⁸Ga-labelled tracer HA-DOTATATE to be comparable to other ⁶⁸Ga-labelled SSR analogues in clinical use. Ziel: ⁶⁸Ga-markierte Verbindungen werden für die Somatostatinrezeptor-Szintigrafie wegen ihrer günstigen biokinetischen Eigenschaften, dem höheren Tumor-zu-Untergrund-Kontrast und der höheren diagnostischen Sicherheit imVergleich zum gammaemittierenden ¹¹¹In- DTPA-Octreotid eingesetzt. Vor kurzem wurde der neue Tracer ⁶⁸Ga-DOTA-3-Iod-Tyr3- Thr8-octreotid (⁶⁸Ga-HA-DOTATATE) eingeführt. Diese Studie zeigt die Biodistribution sowie die Strahlenexposition dieses Tracers im Menschen. Patienten, Methoden: Sieben Männer wurden in die Studie eingeschlossen. Jeder Patient wurde nach intravenösen Injektion von 114 ± 9 MBq von ⁶⁸Ga-HA-DOTATA- TE einer dynamischen PET Untersuchung unterzogen (Dauer: 20 min). Danach erfolgten Ganzkörperscans 30 und 120 Minuten p. i. Die Blutradioaktivitätskonzentration wurde nicht-invasiv aus einer über die Aorta gelegten ROI bestimmt. Urin wurde bis zur letzten Untersuchung gesammelt. Leber, Milz, Nieren und Harnblasenwand wurden in die dosime- trischen Berechnungen eingeschlossen, diese erfolgten mit dem Programm OLINDA 1.0. Ergebnisse: Physiologische Anreicherungen von ⁶⁸Ga-HA-DOTATATE wurden in der Hypophyse, der Schilddrüse, den Speicheldrüsen, der Leber, der Milz, den Nieren, der Harnblase, den Nebennieren und dem Darm beobachtet. Die Organe mit der höchsten absorbierten Dosis waren die Milz (0,26 ± 0,11 mSv/MBq), die Nieren (0,14 ± 0,03 mSv/MBq) und die Leber (0,12 ± 0,02 mSv/MBq). Die effektive Dosis betrug 0,024 ± 0,001 mSv/MBq. Schlussfolgerung: Unsere Studie zeigt, dass die Biodistribution und Strahlenexposition des ⁶⁸Ga- markierten Tracers HA-DOTATATE mit anderen ⁶⁸Ga-markierten SSR-Tracern im klinischen Gebrauch vergleichbar ist.

The interest in the detection of radioactive materials has strongly increased after the accident in the nuclear power plant Fukushima and has led to a bottleneck of suitable measuring instruments. Smartphones equipped with a commercially available software tool could be used for dose rate measurements following a calibration according to the specific camera module. Aim: We examined whether such measurements provide reliable data for typical activities and radionuclides in nuclear medicine. Methods: For the nuclides ^99mTc (10 – 1000 MBq), ¹³¹I (3.7 – 1800 MBq, therapy capsule) and ⁶⁸Ga (50 – 600 MBq) radioactivity with defined geo metry in different distances was measured. The smartphones Milestone Droid 1 (Motorola) and HTC Desire (HTC Corporation) were compared with the standard instruments AD6 (automess) and DoseGUARD (AEA Technology). Results: Measurements with the smartphones and the other devices show a good agreement: linear signal increase with rising activity and dose rate. The long time measurement (¹³¹I, 729 MBq, 0.5 m, 60 min) demonstrates a considerably higher variation (by 20%) of the measured smartphone data values compared with the AD6. For low dose rates (< 1 μGy/h), the sensitivity decreases so that measurements of e. g. the natural radiation exposure do not lead to valid results. The calibration of the camera responsivity for the smartphone has a big influence on the results caused by the small detector surface of the camera semiconductor. Conclusions: With commercial software the camera module of a smartphone can be used for the measurement of radioactivity. Dose rates resulting from typical nuclear medicine procedures can be measured reliably (e. g., dismissal dose after radioiodine therapy). The signal shows a high correlation to measured values of conventional dose measurement devices. Das Interesse am Nachweis von radioaktiven Stoffen hat nach dem jüngsten Unfall im Kernkraftwerk Fukushima stark zugenommen und zu einem Engpass bei entsprechenden Messgeräten geführt. Für den Einsatz des Kamerasystems von Smartphones zum Strahlungsnachweis existiert eine kommerzielle Software welche die Nutzung als Dosisleistungsmessgerät unter Verwendung gerätespezifischer Kalibrierdaten erlaubt. Ziel: Wir untersuchten, ob die Anwendung für in der Nuklearmedizin übliche Nuklide und Radioaktivitätsmengen möglich ist. Methodik: Für die Nuklide ^99mTc (10–1000 MBq), ¹³¹I (3,7–1800 MBq, Therapiekapsel) und ⁶⁸Ga (50–600 MBq) wurden Messungen in definierter Geometrie in verschiedenen Abständen durchgeführt. Die Smartphones Milestone Droid 1 (Motorola) und HTC Desire (HTC Corporation) wurden mit den Messgeräten AD6 (automess) und DoseGUARD (AEA Technology) verglichen. Ergebnisse: Die Messwerte der Smartphones und der anderen Geräte sind gut miteinander vergleichbar: linearer Signalanstieg bei zunehmender Aktivität und Dosis leistung. Langzeitmessungen (¹³¹I, 729 MBq, 0,5 m, 60 min) ergaben bei Smartphones Werte, die um 20% schwankten im Vergleich zu AD6. Smartphones haben im Bereich niedriger Dosisleistung (< 1 μGy/h) deutliche Empfindlichkeitsverluste. Messungen im Bereich der natürlichen Radioaktivität ergaben keine validen Anzeigewerte. Die individuelle Kalibrierung der Empfindlichkeit auf den Smartphonetyp übt großen Einfluss auf die Messwertanzeige aus wegen der unterschiedlichen Kameramodule. Schlussfolgerungen: Mit Hilfe kommerzieller Software lässt sich das Kameramodul eines Smartphones zum Radioaktivitätsnachweis nutzen. Typische Nuklide der Nuklearmedizin können in relevanten Aktivitätsmengen (z. B. Entlassungdosis nach Radioiodtherapie) sicher nachgewiesen werden. Das Signal korreliert mit den Messwerten klassischer Strahlungsdetektionsgeräte in hohem Maße.

Summary: Aim: Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOCfor patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. Patients, methods: Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112 ± 22) MBq 68Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/ EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). Results: Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. Conclusion: 68Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).