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This review presents efforts in Europe over the last few years with respect to standardization of quantitative imaging and dosimetry and comprises the results of several European research projects on practices regarding radiopharmaceutical therapies (RPTs). Because the European Union has regulatory requirements concerning dosimetry in RPTs, the European Association of Nuclear Medicine released a position paper in 2021 on the use of dosimetry under these requirements. The importance of radiobiology for RPTs is elucidated in another position paper by the European Association of Nuclear Medicine. Furthermore, how dosimetry interacts with clinical requirements is described, with several clinical examples. In the future, more efforts need to be undertaken to increase teaching and standardization efforts and to incorporate radiobiology for further individualizing patient treatment, with the aim of improving the outcome and safety of RPTs.

Aim The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [131I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy. Material and methods Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [131I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70% ethanol and stored at − 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs). Results Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h−1, which is in good agreement with data obtained from external irradiation with γ- or X-rays. Conclusion This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after 131I exposure is comparable to that of external irradiation with γ- or X-rays.

Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

The aim of this review is to provide an overview of the most recent technologic developments in state-of-the-art equipment and tools for dosimetry in radionuclide therapies. This includes, but is not restricted to, calibration methods for imaging systems. In addition, a summary of new developments that consider the influence of small-scale dosimetry and of biologic effects on radionuclide therapies is given. Finally, the current limitations of patient-specific dosimetry such as bone-marrow dosimetry or dosimetry of α-emitters are discussed.

ZusammenfassungDie Biodosimetrie leistet einen wichtigen Beitrag zum Verständnis der Wirkung ionisierender Strahlung. Ziel dieser Übersichtsarbeit ist es daher, Methoden und Ergebnisse der Biodosimetrie und deren Zusammenhang mit der physikalischen Dosimetrie vorzustellen. Die Daten dieser Arbeit wurden aus Veröffentlichungen nach 1995 erhoben. Die dabei verwendeten Methoden sind hauptsächlich die Analyse dizentrischer Chromosomen, der Mikrokern-Assay, sowie der γ-H2AX-Assay in Lymphozyten. Die Mehrzahl der Daten wurde während Radioiodtherapien erhoben. Etwa die Hälfte der Veröffentlichungen bezog die Ergebnisse nur auf die verabreichte Aktivität. Dosis-Wirkungsbeziehungen konnten nur in wenigen Arbeiten hergestellt werden. Insbesondere anhand der Daten, die mittels des γ-H2AX-Assays gewonnen wurden, konnte die Dosisabhängigkeit und der zeitliche Verlauf der DNA-Schadensantwort in vitro und in vivo mit ß–-Emittern gezeigt werden. Weitere Arbeiten sind nötig, um die Reparatur von DNA-Schäden und deren Zusammenhang mit der Energiedosis nach nuklearmedizinischer Diagnostik und Therapie, insbesondere auch mit α-Strahlern, noch besser beschreiben zu können.

Purpose The aim of this study was to investigate the time- and dose-dependency of DNA double-strand break (DSB) induction and repair in peripheral blood leucocytes of prostate cancer patients during therapy with 177Lu-PSMA. Methods Blood samples from 16 prostate cancer patients receiving their first 177Lu-PSMA therapy were taken before and at seven time-points (between 1 h and 96 h) after radionuclide administration. Absorbed doses to the blood were calculated using integrated time–activity curves of the blood and the whole-body. For DSB quantification, leucocytes were isolated, fixed in ethanol and immunostained with γ-H2AX and 53BP1 antibodies. Colocalizing foci of both DSB markers were manually counted in a fluorescence microscope. Results The average number of radiation-induced foci (RIF) per cell increased within the first 4 h after administration, followed by a decrease indicating DNA repair. The number of RIF during the first 2.6 h correlated linearly with the absorbed dose to the blood (R2 = 0.58), in good agreement with previously published in-vitro data. At late time-points (48 h and 96 h after administration), the number of RIF correlated linearly with the absorbed dose rate (R2 = 0.56). In most patients, DNA DSBs were repaired effectively. However, in some patients RIF did not disappear completely even 96 h after administration. Conclusion The general pattern of the time- and dose-dependent induction and disappearance of RIF during 177Lu-PSMA therapy is similar to that of other radionuclide therapies.

(18)F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. (18)F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of (18)F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of (18)F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that (18)F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether (18)F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors.

Systemic or locoregionally administered alpha-particle emitters are highly potent therapeutic agents used in oncology that are fundamentally novel in their mechanism and, most likely, overcome radiation resistance as the alpha particles emitted have a short range and a high linear energy transfer. The use of alpha emitters in a clinic environment requires extra measures with respect to imaging, dosimetry, and radiation protection. This is shown for the example of 223Ra dichloride therapy. After intravenous injection, 223Ra leaves the blood and is taken up rapidly in bone and bone metastases; it is mainly excreted via the intestinal tract. 223Ra can be imaged in patients with a gamma camera. Dosimetry shows that, after a series of six treatments for a 70-kg person with an overall administered activity of 23 MBq, 223Ra results in an absorbed alpha dose of approximately 17 Gy to the bone endosteum and approximately 1.7 Gy to the red bone marrow. During administration, special care must be taken to ensure that no spill is present on the skin of either the patient or staff. Due to the low dose rate, the treatment is normally performed on an outpatient basis; the patient and carers should receive written instructions about the therapy and radiation protection.

UnlabelledProstate-specific membrane antigen (PSMA) is a promising target for diagnosis and treatment of prostate cancer. EuK-Subkff-(68)Ga-DOTAGA ((68)Ga-PSMA Imaging & Therapy [PSMA I&T]) is a recently introduced PET tracer for imaging PSMA expression in vivo. Whole-body distribution and radiation dosimetry of this new probe were evaluated.MethodsFive patients with a history of prostate cancer were injected intravenously with 91-148 MBq of (68)Ga-PSMA I&T (mean ± SD, 128 ± 23 MBq). After an initial series of rapid whole-body scans, 3 static whole-body scans were acquired at 1, 2, and 4 h after tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM.ResultsInjection of 150 MBq of (68)Ga-PSMA I&T resulted in an effective dose of 3.0 mSv. The kidneys were the critical organ (33 mGy), followed by the urinary bladder wall and spleen (10 mGy each), salivary glands (9 mGy each), and liver (7 mGy).Conclusion(68)Ga-PSMA I&T exhibits a favorable dosimetry, delivering organ doses that are comparable to (kidneys) or lower than those delivered by (18)F-FDG.

68Ga-pentixafor is a promising PET tracer for imaging the expression of the human chemokine receptor 4 (CXCR4) in vivo. The whole-body distribution and radiation dosimetry of 68Ga-pentixafor were evaluated. Methods: Five multiple-myeloma patients were injected intravenously with 90–158 MBq of 68Ga-pentixafor (mean ± SD, 134 ± 25 MBq), and a series of 3 rapid multiple-bed-position whole-body scans were acquired immediately afterward. Subsequently, 4 static whole-body scans followed at 30 min, 1 h, 2 h, and 4 h after administration of the radiopharmaceutical. Venous blood samples were obtained. Time-integrated activity coefficients were determined from multiexponential regression of organ region-of-interest data normalized to the administered activity, for example, the time-dependent percentages of the injected activity per organ. Mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Results: The effective dose based on 150 MBq of 68Ga-pentixafor was 2.3 mSv. The highest organ-absorbed doses (for 150 MBq injected) were found in the urinary bladder wall (12.2 mGy), spleen (8.1 mGy), kidneys (5.3 mGy), and heart wall (4.0 mGy). Other organ mean absorbed doses were as follows: 2.7 mGy, liver; 2.1 mGy, red marrow; 1.7 mGy, testes; and 1.9 mGy, ovaries. Conclusion:68Ga-pentixafor exhibits a favorable dosimetry, delivering absorbed doses to organs that are lower than those delivered by 18F-FDG– or 68Ga-labeled somatostatin receptor ligands.

In 2005, the term theragnostics (theranostics) was introduced for describing the use of imaging for therapy planning in radiation oncology. In nuclear medicine, this expression describes the use of tracers for predicting the absorbed doses in molecular radiotherapy and, thus, the safety and efficacy of a treatment. At present, the most successful groups of isotopes for this purpose are 123I/124I/131I, 68Ga/177Lu, and 111In/86Y/90Y. The purpose of this review is to summarize available data on the dosimetry and dose-response relationships of several theranostic compounds, with a special focus on radioiodine therapy for differentiated thyroid cancer and peptide receptor radionuclide therapy. These are treatment modalities for which dose-response relationships for healthy tissues and tumors have been demonstrated. In addition, available data demonstrate that posttherapeutic dosimetry after a first treatment cycle predicts the absorbed doses in further cycles. Both examples show the applicability of the concept of theranostics in molecular radiotherapies. Nevertheless, unanswered questions need to be addressed in clinical trials incorporating dosimetry-related concepts for determining the amount of therapeutic activity to be administered.

International audience; The “intended purpose” in all therapeutic exposures is treatment efficacy against malignant disease. The optimization principle (as low as reasonably achievable, ALARA) of article 56, when applied in a therapy situation, states that absorbed doses to nontarget tissues should be kept reasonably low, but not so low as to lose efficacy. We think that this applies above all to the fight against life-threatening cancer. As a consequence, we believe that to adhere to the optimization principle in oncological patients, nuclear medicine therapy should be based on individualized dosimetry.

Nuclear medicine dosimetry and research in biodosimetry often require the knowledge of the absorbed dose to the blood. This study provides coefficients for the absorbed dose rates to the blood related to the activity concentration in the blood as a function of the vessel radius for radionuclides commonly used in targeted radiotherapy and in PET-diagnostics: C-11, F-18, Ga-68, Y-90, Tc-99 m, I-124, I-131, and Lu-177. The energy deposition patterns after nuclear disintegrations in blood vessel lumina (cylinders homogeneously filled with blood) with radii from 0.01 to 25.0 mm were simulated with the Monte-Carlo radiation transport code MCNPX. An additional contribution from photon radiation from activity in blood in the remainder of the body was taken into account based on a reasonable blood distribution model. The fraction of energy absorbed from non-penetrating radiation in the blood is low in thin blood vessels but approaches the total energy emitted by particles with increasing lumen radius. For photon radiation, irradiation to blood in small vessels is almost completely due to radioactive decays in distant blood distributed throughout the body, whereas the contribution from activity in the vessel becomes dominant for lumen radii exceeding 13 mm. The dependences of the absorbed dose rates on the lumen radius can be described with good accuracy by empirical functions which can be used to determine the absorbed doses to the blood and to the surrounding tissue.

In recent years internal dosimetry added valuable information on the diagnostic and therapeutic use of radionuclide imaging and therapy of neuroendocrine tumors.

This review compiles and analyzes the available dosimetry data of [ 68 Ga] labeled compounds. Dosimetry data are given for [ 68 Ga]DOTA-NOC, TOC, TATE, and NODAGA-RGDyK. The number of PET-scans with [ 68 Ga]DOTA-compounds for imaging neuroendocrine tumors is increasing because [ 68 Ga] has a higher affinity to somatostatin receptors (SSTR) in comparison to comparable [ 111 In]-compounds. In addition, the better image resolution of the PET images provides improved diagnostics. Despite its widespread use literature on dosimetry of [ 68 Ga]-labeled radiopharmaceuticals is sparse. In some cases the description of the underlying methodology is missing or human data are gained from the extrapolation of animal experiments. More and better documented dosimetry data will further promote the use of these promising new agents.

Die Koregistrierung von CT-Daten im Rahmen nuklearmedizinischer Untersuchungen erlaubt eine direkte Korrelation anatomischer und funktioneller Informationen. Szintigrafische Befunde konnen so prazise lokalisiert und die Dignitat unklarer CT-Befunde aufgrund funktioneller Daten beurteilt werden. Bei zahlreichen onkologischen Fragestellungen konnte eine Uberlegenheit der Hybridtechnik gegenuber separat durchgefuhrter anatomischer und funktioneller Untersuchungen gezeigt werden. Die Einfuhrung der PET/CT in die klinische Diagnostik hat aufgrund einer hohen diagnostischen Treffsicherheit zu einer Anderung des Diagnose-Algorithmus einiger solider Tumoren und hamatologischer Neoplasien gefuhrt. Bezuglich SPECT/CT konnte eine verbesserte Diagnostik von Knochenmetastasen, neuroendokrinen Tumoren und von Wachterlymphknoten bei Erstdiagnose eines Mammakarzinoms oder malignen Melanoms belegt werden. Die Anzahl der mittels Hybridgeraten durchgefuhrten Untersuchungen gehort zu den am schnellsten wachsenden unter den bildgebenden Verfahren in der Medizin. Mit zunehmender Untersuchungsfrequenz ruckt die Minimierung der Strahlenexposition immer mehr in den Fokus und der Untersuchungsablauf wird kontinuierlich optimiert. Viele onkologische Fragestellungen konnen bereits mit einer ’low-dose´-PET/CT- oder -SPECT/CT-Untersuchung hinreichend beantwortet werden. Durch die Verwendung der neuesten Geratetechnik kann die Strahlenexposition sowohl seitens der CT als auch durch die applizierte Aktivitat der Radiopharmaka wesentlich beeinflusst werden. Dieser Artikel soll eine Ubersicht uber die mit Hybriduntersuchungen verbundene Strahlenexposition geben und zeigen, wie diese bereits heute signifikant reduziert werden kann. Entscheidend ist, dass ionisierende Strahlung nur bei eindeutigen klinischen Fragestellungen zum Einsatz kommen darf.

Diagnostic nuclear medicine procedures imply the administration of activity levels that do not lead to the appearance of radiation deterministic effects. Effects to be expected, if at all, are stochastic effects of ionizing radiation. The assessment of adverse health effects from exposure of ionizing radiation in the dose range commonly encountered in clinical (and pediatric) diagnostic nuclear medicine is based on epidemiological and biological data. Most of the data on the effects on human health after exposure to ionizing radiation comes from the Life Span Study of the survivors of the bombings of Hiroshima and Nagasaki, as reported by the Radiation Effects Research Foundation [18, 22–24]. In addition, there are few data on the stochastic radiation risk after treatment of thyroid diseases with radioiodine [10, 21, 26, 31]. However, there is no clear evidence that there is an increase in cancer risk associated with I-131 therapy [31]. No such data are available concerning the potential cancer risk of diagnostic nuclear medicine.

Radioguided surgery requires a significant amount of technology for its implementation. As a result, surgeons working in this field must have a basic know-how that extends beyond the standard surgical training and covers the relevant physics. Within this chapter we have tried to synthesize the background knowledge needed for a complete understanding of the most important aspects and processes. The terminology and the explanations target people just starting in the field, and the contents should prove readily intelligible as long as the complete chapter is read.

The use of radioactive substances for sentinel lymph node (SLN) biopsy needs consideration on how to optimize radiation safety issues. In this chapter an overview on basic radiation-related quantities, definitions, and on patient dosimetry is given. Values of absorbed and effective doses are provided for patients, the staff in the operation theater and in the pathology department, and for waste disposal. For radiolocalization of SLN with Tc-99m, the dose to the patients and the exposure of the staff are low; for radiopharmaceuticals with longer half-lives and/or positron emitters, individual monitoring of staff exposure and contamination should be considered for larger patient numbers.

The aim of the study was to investigate DNA double-strand break (DSB) formation and its correlation to the absorbed dose to the blood in patients with surgically treated differentiated thyroid cancer undergoing their first radioiodine therapy for remnant ablation. Methods: Twenty patients were included in this study. At least 7 peripheral blood samples were obtained before and between 0.5 and 120 h after administration of radioiodine. From the time–activity curves of the blood and the whole body, residence times for the blood self-irradiation and the irradiation from the whole body were determined. Peripheral blood lymphocytes were isolated, ethanol-fixed, and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was analyzed as a function of the absorbed dose to the blood and compared with an in vitro calibration curve for 131I and 177Lu established previously in our institution. Results: The average number of radiation-induced foci (RIF) per cell increased over the first 3 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 2 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time points, RIF numbers diminished, along with dropping dose rates, indicating progression of DNA repair. Individual patient data were characterized by a linear dose-dependent increase and a biexponential response function describing a fast and a slow repair component. Conclusion: With the experimental results and model calculations presented in this work, a dose–response relationship is demonstrated, and an analytic function describing the time course of the in vivo damage response after internal irradiation of patients with 131I is established.

For diagnostic dosimetry in nuclear medicine, quantitative imaging and activity measurements of blood and urine samples are essential. This is followed by the calculation of the absorbed organ doses and the effective dose. To achieve this, a correct temporal sampling and the use of adequate procedures to integrate the time-activity curves to obtain the total number of decays in the source organs (the time-integrated activity coefficients, TIACs) are prerequisites. If the TIACs are known, a calculation of the absorbed doses is performed by applying the “MIRD formalism”: D = TIAC · A 0 · S D: the mean absorbed dose to a target from a source region. A 0 : administered activity S: mean absorbed dose per unit cumulated activity in the target region. The S-values used for diagnostics are still based on mathematical phantoms. Although, the ICRP in its publication 103 requires the use of a set of gender-specific realistic voxel phantoms, the S-values for isotopes, however, are not yet made publicly available. For diagnostics the effective dose is the main protection quantity. It is calculated using the tissue weighting factors established by the ICRP in the publications ICRP60 and ICRP103. The effective dose, however, is only intended to calculate the risk for an age-independent reference person, not the individual risk. It is a protection quantity and is related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation.

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained. Electronic supplementary material The online version of this article (doi:10.1007/s00259-011-1904-z) contains supplementary material, which is available to authorized users.

Purpose The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with 177Lu-labelled DOTATATE/DOTATOC. Methods The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time–activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with 131I and 177Lu. Results The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Conclusion Measurements of RIF and the absorbed dose to the blood after systemic administration of 177Lu may be used to obtain data on the individual dose–response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. Electronic supplementary material The online version of this article (doi:10.1007/s00259-015-3083-9) contains supplementary material, which is available to authorized users.

PurposeThe aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.MethodsSeveral conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.ResultsQuantitative labeling yields could be achieved with >97% radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p