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The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.

PurposeA multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres.MethodsA steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%).ResultsForty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement).ConclusionPractitioners are encouraged to work towards adoption of these recommendations.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18 F-FDG imaging. We compared the physiological 18 F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2–20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0–5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18 F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new “higher” SUV of the normal 18 F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

BackgroundExtrapolation of human absorbed doses (ADs) from biodistribution experiments on laboratory animals is used to predict the efficacy and toxicity profiles of new radiopharmaceuticals. Comparative studies between available animal-to-human dosimetry extrapolation methods are missing. We compared five computational methods for mice-to-human AD extrapolations, using two different radiopharmaceuticals, namely [111In]CHX-DTPA-scFv78-Fc and [68Ga]NODAGA-RGDyK. Human organ-specific time-integrated activity coefficients (TIACs) were derived from biodistribution studies previously conducted in our centre. The five computational methods adopted are based on simple direct application of mice TIACs to human organs (M1), relative mass scaling (M2), metabolic time scaling (M3), combined mass and time scaling (M4), and organ-specific allometric scaling (M5), respectively. For [68Ga]NODAGA-RGDyK, these methods for mice-to-human extrapolations were tested against the ADs obtained on patients, previously published by our group. Lastly, an average [68Ga]NODAGA-RGDyK-specific allometric parameter αnew was calculated from the organ-specific biological half-lives in mouse and humans and retrospectively applied to M3 and M4 to assess differences in human AD predictions with the α = 0.25 recommended by previous studies.ResultsFor both radiopharmaceuticals, the five extrapolation methods showed significantly different AD results (p < 0.0001). In general, organ ADs obtained with M3 were higher than those obtained with the other methods. For [68Ga]NODAGA-RGDyK, no significant differences were found between ADs calculated with M3 and those obtained directly on human subjects (H) (p = 0.99; average M3/H AD ratio = 1.03). All other methods for dose extrapolations resulted in ADs significantly different from those calculated directly on humans (all p ≤ 0.0001). Organ-specific allometric parameters calculated using combined experimental [68Ga]NODAGA-RGDyK mice and human biodistribution data varied significantly. ADs calculated with M3 and M4 after the application of αnew = 0.17 were significantly different from those obtained by the application of α = 0.25 (both p < 0.001).ConclusionsAvailable methods for mouse-to-human dosimetry extrapolations provided significantly different results in two different experimental models. For [68Ga]NODAGA-RGDyK, the best approximation of human dosimetry was shown by M3, applying a metabolic scaling to the mouse organ TIACs. The accuracy of more refined extrapolation algorithms adopting model-specific metabolic scaling parameters should be further investigated.

First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver’s disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99m Tc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90 Y-PET/CT and assess the dose–response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43–82). Patients underwent MRI/CT, 18 F-FDG-PET/CT before and 3–6 months post-SIRT, and 90 Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99m Tc-MAA-SPECT/CT and post-SIRT 90 Y-PET/CT, and assessed with Lin’s concordance correlation coefficients ( ρ c and C b ), Pearson’s coefficient correlation ( ρ ), and Bland–Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46–1586 Gy). Concordance between 99m Tc-MAA-SPECT/CT and 90 Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) ( ρ  = 0.725, ρ c  = 0.703, C b  = 0.969) with good agreement (mean difference: − 4.93 ± 218.3 Gy, 95%LOA: − 432.8–422.9). Without RC correction, concordance was better for resin microspheres ( ρ  = 0.85, ρ c  = 0.998, C b  = 0.849) and agreement was very good between predictive 99m Tc-MAA-SPECT/CT and 90 Y-PET/CT dosimetry (mean difference: − 4.05 ± 55.9 Gy; 95%LOA: − 113.7–105.6). After RC correction, 99m Tc-MAA-SPECT/CT dosimetry overestimated AD (− 70.9 ± 158.9 Gy; 95%LOA: − 382.3–240.6). For glass microspheres, concordance markedly improved with RC correction ( ρ  = 0.790, ρ c  = 0.713, C b  = 0.903 vs without correction: ρ  = 0.395, ρ c  = 0.244, C b  = 0.617) and 99m Tc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: − 375.4–673.2). For non-tumor liver, concordance was good between 99m Tc-MAA-SPECT/CT and 90 Y-PET/CT dosimetry ( ρ  = 0.942, ρ c  = 0.852, C b  = 0.904). 99m Tc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose–response threshold could be identified. 99m Tc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

BackgroundThe folate receptor alpha (FRα) is an interesting target for imaging and therapy of different cancers. We present the first in-human radiation dosimetry and radiation safety results acquired within a prospective, multicentric trial (NCT03242993) evaluating the 18F-AzaFol (3′-aza-2′-[18F]fluorofolic acid) as the first clinically assessed PET tracer targeting the FRα.Material and methodsSix eligible patients presented a histologically confirmed adenocarcinoma of the lung with measurable lesions (≥ 10 mm according to RECIST 1.1). TOF-PET images were acquired at 3, 11, 18, 30, 40, 50, and 60 min after the intravenous injection of 327 MBq (range 299–399 MBq) of 18F-AzaFol to establish dosimetry. Organ absorbed doses (AD), tumor AD, and patient effective doses (E) were assessed using the OLINDA/EXM v.2.0 software and compared with pre-clinical results.ResultsNo serious related adverse events were observed. The highest AD were in the liver, the kidneys, the urinary bladder, and the spleen (51.9, 45.8, 39.1, and 35.4 μGy/MBq, respectively). Estimated patient and gender-averaged E were 18.0 ± 2.6 and 19.7 ± 1.4 μSv/MBq, respectively. E in-human exceeded the value of 14.0 μSv/MBq extrapolated from pre-clinical data. Average tumor AD was 34.8 μGy/MBq (range 13.6–60.5 μGy/MBq).Conclusions18F-Azafol is a PET agent with favorable dosimetric properties and a reasonable radiation dose burden for patients which merits further evaluation to assess its performance.Trial registrationClinicalTrial.gov, NCT03242993, posted on August 8, 2017

Background We aimed to estimate 82 Rb paediatric dosimetry based on adult biokinetic and prospectively acquired paediatric biokinetic data. Organ absorbed doses (OAD) and effective doses (E) were estimated using ICRP-103 based OLINDA/EXM.2.1 software. We extrapolated paediatric OAD and E from existing adult biokinetic data (OAD p, Ab and E p, Ab respectively). 82 Rb EANM paediatric dosage card (PDC) cluster and the recommended administered activity were determined. Ten paediatric participants (M: F 7:3; mean age 8.8 ± 6.6y) underwent prospectively 3D-SiPM 82 Rb PET/CT. Using PMOD software, source organs volumes were delineated to obtain source organ time activity curves and participant specific organ masses based on PET/CT data. Subject specific OAD (OAD p and E p respectively) were derived from original paediatric data. Results 82 Rb was assigned to the EANM PDC B-Cluster. Estimated ranges for E p, Ab resp. E p were 2.19E-02 ̶ 1.15E-03 resp. 9.62E-03 ̶ 1.04E-03 mSv/MBq. E p, Ab resp. E p with 10 MBq/kg and 5MBq/kg after a single 82 Rb infusion was between 0.5 and 0.7 mSv resp. 0.4–0.8 mSv and 0.2–0.4 mSv. The most irradiated organs were the kidneys and the heart wall in infant and newborn group, followed by heart wall in the other age groups, hence, the small intestine, pancreas, lungs, adrenals, and rest of the gastrointestinal tract. 82 Rb PET/CT was safe and well-tolerated by all participants. Conclusions We firstly provide original dosimetry data for the use of 82 Rb PET/CT in the paediatric population, showing reasonably low radiation exposure, and confirming safety and tolerability of 82 Rb PET/CT in this population.

BackgroundWe assessed and compared image quality obtained with clinical 18F-FDG whole-body oncologic PET protocols used in three different, state-of-the-art digital PET/CT and two conventional PMT-based PET/CT devices.Our goal was to evaluate an improved trade-off between administered activity (patient dose exposure/signal-to-noise ratio) and acquisition time (patient comfort) while preserving diagnostic information achievable with the recently introduced digital detector technology compared to previous analogue PET technology.MethodsWe performed list-mode (LM) PET acquisitions using a NEMA/IEC NU2 phantom, with activity concentrations of 5 kBq/mL and 25 kBq/mL for the background (9.5 L) and sphere inserts, respectively. For each device, reconstructions were obtained varying the image statistics (10, 30, 60, 90, 120, 180, and 300 s from LM data) and the number of iterations (range 1 to 10) in addition to the employed local clinical protocol setup. We measured for each reconstructed dataset: the quantitative cross-calibration, the image noise on the uniform background assessed by the coefficient of variation (COV), and the recovery coefficients (RCs) evaluated in the hot spheres. Additionally, we compared the characteristic time-activity-product (TAP) that is the product of scan time per bed position × mass-activity administered (in min·MBq/kg) across datasets.ResultsGood system cross-calibration was obtained for all tested datasets with < 6% deviation from the expected value was observed. For all clinical protocol settings, image noise was compatible with clinical interpretation (COV < 15%). Digital PET showed an improved background signal-to-noise ratio as compared to conventional PMT-based PET. RCs were comparable between digital and PMT-based PET datasets. Compared to PMT-based PET, digital systems provided comparable image quality with lower TAP (from ~ 40% less and up to 70% less).ConclusionsThis study compared the achievable clinical image quality in three state-of-the-art digital PET/CT devices (from different vendors) as well as in two conventional PMT-based PET. Reported results show that a comparable image quality is achievable with a TAP reduction of ~ 40% in digital PET. This could lead to a significant reduction of the administered mass-activity and/or scan time with direct benefits in terms of dose exposure and patient comfort.

Background Several research groups have explored the potential of scandium radionuclides for theragnostic applications due to their longer half-lives and equal or similar coordination chemistry between their diagnostic and therapeutic counterparts, as well as lutetium-177 and terbium-161, respectively. Unlike the gallium-68/lutetium-177 pair, which may show different in-vivo uptake patterns, the use of scandium radioisotopes promises consistent behaviour between diagnostic and therapeutic radiopeptides. An advantage of scandium’s longer half-life over gallium-68 is the ability to study radiopeptide uptake over extended periods and its suitability for centralized production and distribution. However, concerns arise from scandium-44’s decay characteristics and scandium-43’s high production costs. This study aimed to evaluate the dosimetric implications of using scandium radioisotopes with somatostatin analogues against gallium-68 for PET imaging of neuroendocrine tumours. Methods Absorbed dose per injected activity (AD/IA) from the generated time-integrated activity curve (TIAC) were estimated using the radiopeptides [ 43/44/44m Sc]Sc- and [ 68 Ga]Ga-DOTATATE. The kidneys, liver, spleen, and red bone marrow (RBM) were selected for dose estimation studies. The EGSnrc and MCNP6.1 Monte Carlo (MC) codes were used with female (AF) and male (AM) ICRP phantoms. The results were compared to Olinda/EXM software, and the effective dose concentrations assessed, varying composition between the scandium radioisotopes. Results Our findings showed good agreement between the MC codes, with − 3 ± 8% mean difference. Kidneys, liver, and spleen showed differences between the MC codes (min and max) in a range of − 4% to 8%. This was observed for both phantoms for all radiopeptides used in the study. Compared to Olinda/EXM the largest observed difference was for the RBM, of 21% for the AF and 16% for the AM for scandium- and gallium-based radiopeptides. Despite the differences, our findings showed a higher absorbed dose on [ 43/44 Sc]Sc-DOTATATE compared to its 68 Ga-based counterpart. Conclusion This study found that [ 43/44 Sc]Sc-DOTATATE delivers a higher absorbed dose to organs at risk compared to [ 68 Ga]Ga-DOTATATE, assuming equal distribution. This is due to the longer half-life of scandium radioisotopes compared to gallium-68. However, calculated doses are within acceptable ranges, making scandium radioisotopes a feasible replacement for gallium-68 in PET imaging, potentially offering enhanced diagnostic potential with later timepoint imaging.

Purpose Therapeutic administration of 90 Y-loaded microspheres is routinely used for primary and secondary liver tumours. For activity-based therapeutic prescription the activity must be within 10% of the intended activity. Previous studies reported significant discrepancies between manufacturer-declared vial activities and both experimental and Monte-Carlo assessments, greater than 10%, for resin/glass 90 Y-microspheres. The objective of this work was to investigate whether these discrepancies were also seen in patients. Methods We analysed patient 90 Y-PET reconstructions (99 glass and 15 resin microspheres) from 4 different institutions and 4 different systems. We considered tail-fitting background scaling (TFBS) and absolute scaling (ABS), for scatter correction. Residuals after therapeutic injection were measured. Eighty-one patients were imaged with PET/CT and 33 with PET/MR. The PET measured activity (A PET ) was assessed in the whole liver. The ratio A PET /A calibrator was calculated for each patient, where A calibrator was the injected activity measured by the dose calibrator corrected for residual and lung shunt. Results Quantification ratio between calibrators and PET was significantly different from 1, regardless of the scatter correction used. In glass microspheres, the mean A PET/CT /A calibrator was 0.84 ± 0.06 for TFBS and 0.90 ± 0.06 for ABS (0.66 ± 0.09 and 0.76 ± 0.07 for (A PET/MR /A calibrator )). The mean A PET/CT /A calibrator ratio for resin microspheres was 1.16 ± 0.09 for TFBS and 1.30 ± 0.12 for ABS. Conclusions We observed in patients similar activity discrepancies as reported for vials, with a relative difference of 44 ± 16% between glass and resin 90 Y-loaded microspheres. In 90 Y hepatic radioembolization, the 10% accuracy prerequisite on knowing the administered therapeutic activity is then unlikely to be met.