Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging.

PURPOSE: This study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging. METHODS: Three Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference. RESULTS: Considering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. CONCLUSION: The hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE.

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [177Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [177Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [177Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.

Kidney dosimetry in [177Lu]Lu-DOTA-TATE therapy based on multiple small VOIs.

PURPOSE: The aim was to investigate the use of multiple small VOIs for kidney dosimetry in [177Lu]Lu-DOTA-TATE therapy. METHOD: The study was based on patient and simulated SPECT images in anthropomorphic geometries. Images were reconstructed using two reconstruction programs (local LundaDose and commercial Hermia) using OS-EM with and without resolution recovery (RR). Five small VOIs were placed to determine the average activity concentration (AC) in each kidney. The study consisted of three steps: (i) determination of the number of iterations for AC convergence based on simulated images; (ii) determination of recovery-coefficients (RCs) for 2 mL VOIs using a separate set of simulated images; (iii) assessment of operator variability in AC estimates for simulated and patient images. Five operators placed the VOIs, using for guidance: a) SPECT/CT with RR, b) SPECT/CT without RR, and c) CT only. For simulated images, time-integrated ACs (TIACs) were evaluated. For patient images, estimated ACs were compared with results of a previous method based on whole-kidney VOIs. RESULTS: Eight iterations and ten subsets were sufficient for both programs and reconstruction settings. Mean RCs (mean ± SD) with RR were 1.03 ± 0.02 (LundaDose) and 1.10 ± 0.03 (Hermia), and without RR 0.91 ± 0.03 (LundaDose) and 0.94 ± 0.03 (Hermia). Most stable and accurate estimates of the AC were obtained using five 2-mL VOIs guided by SPECT/CT with RR, applying them to images without RR, and including an explicit RC for recovery correction. CONCLUSION: The small VOI method based on five 2-mL VOIs was found efficient and sufficiently accurate for kidney dosimetry in [177Lu]Lu-DOTA-TATE therapy.

Feasibility of 177Lu activity quantification using a small portable CZT-based gamma-camera.

BACKGROUND: In image processing for activity quantification, the end goal is to produce a metric that is independent of the measurement geometry. Photon attenuation needs to be accounted for and can be accomplished utilizing spectral information, avoiding the need of additional image acquisitions. The aim of this work is to investigate the feasibility of 177Lu activity quantification with a small CZT-based hand-held gamma-camera, using such an attenuation correction method. METHODS: A previously presented dual photopeak method, based on the differential attenuation for two photon energies, is adapted for the three photopeaks at 55 keV, 113 keV, and 208 keV for 177Lu. The measurement model describes the count rates in each energy window as a function of source depth and activity, accounting for distance-dependent system sensitivity, attenuation, and build-up. Parameter values are estimated from characterizing measurements, and the source depth and activity are obtained by minimizing the difference between measured and modelled count rates. The method is applied and evaluated in phantom measurements, in a clinical setting for superficial lesions in two patients, and in a pre-clinical setting for one human tumour xenograft. Evaluation is made for a LEHR and an MEGP collimator. RESULTS: For phantom measurements at clinically relevant depths, the average (and standard deviation) in activity errors are 17% ± 9.6% (LEHR) and 2.9% ± 3.6% (MEGP). For patient measurements, deviations from activity estimates from planar images from a full-sized gamma-camera are 0% ± 21% (LEHR) and 16% ± 18% (MEGP). For mouse measurements, average deviations of - 16% (LEHR) and - 6% (MEGP) are obtained when compared to a small-animal SPECT/CT system. The MEGP collimator appears to be better suited for activity quantification, yielding a smaller variability in activity estimates, whereas the LEHR results are more severely affected by septal penetration. CONCLUSIONS: Activity quantification for 177Lu using the hand-held camera is found to be feasible. The readily available nature of the hand-held camera may enable more frequent activity quantification in e.g., superficial structures in patients or in the pre-clinical setting.

3D printed non-uniform anthropomorphic phantoms for quantitative SPECT.

BACKGROUND: A 3D printing grid-based method was developed to construct anthropomorphic phantoms with non-uniform activity distributions, to be used for evaluation of quantitative SPECT images. The aims were to characterize the grid-based method and to evaluate its capability to provide realistically shaped phantoms with non-uniform activity distributions. METHODS: Characterization of the grid structures was performed by printing grid-filled spheres. Evaluation was performed by micro-CT imaging to investigate the printing accuracy and by studying the modulation contrast ([Formula: see text]) in SPECT images for 177Lu and 99mTc as a function of the grid fillable-volume fraction (FVF) determined from weighing. The grid-based technique was applied for the construction of two kidney phantoms and two thyroid phantoms, designed using templates from the XCAT digital phantoms. The kidneys were constructed with a hollow outer container shaped as cortex, an inner grid-based structure representing medulla and a solid section representing pelvis. The thyroids consisted of two lobes printed as grid-based structures, with void hot spots within the lobes. The phantoms were filled with solutions of 177Lu (kidneys) or 99mTc (thyroids) and imaged with SPECT. For verification, Monte Carlo simulations of SPECT imaging were performed for activity distributions corresponding to those of the printed phantoms. Measured and simulated SPECT images were compared qualitatively and quantitatively. RESULTS: Micro-CT images showed that printing inaccuracies were mainly uniform across the grid. The relationships between the FVF from weighing and [Formula: see text] were found to be linear (r = 0.9995 and r = 0.9993 for 177Lu and 99mTc, respectively). The FVF-deviations from the design were up to 15% for thyroids and 4% for kidneys, mainly related to possibilities of cleaning after printing. Measured and simulated SPECT images of kidneys and thyroids exhibited similar activity distributions and quantitative comparisons agreed well, thus verifying the grid-based method. CONCLUSIONS: We find the grid-based technique useful for the provision of 3D printed, realistically shaped, phantoms with non-uniform activity distributions, which can be used for evaluation of different quantitative methods in SPECT imaging.

The contest between internal and external-beam dosimetry: The Zeno's paradox of Achilles and the tortoise.

Radionuclide therapy, also called molecular radiotherapy (MRT), has come of age, with several novel radiopharmaceuticals being approved for clinical use or under development in the last decade. External beam radiotherapy (EBRT) is a well-established treatment modality, with about half of all oncologic patients expected to receive at least one external radiation treatment over their disease course. The efficacy and the toxicity of both types of treatment rely on the interaction of radiation with biological tissues. Dosimetry played a fundamental role in the scientific and technological evolution of EBRT, and absorbed doses to the target and to the organs at risk are calculated on a routine basis. In contrast, in MRT the usefulness of internal dosimetry has long been questioned, and a structured path to include absorbed dose calculation is missing. However, following a similar route of development as EBRT, MRT treatments could probably be optimized in a significant proportion of patients, likely based on dosimetry and radiobiology. In the present paper we describe the differences and the similarities between internal and external-beam dosimetry in the context of radiation treatments, and we retrace the main stages of their development over the last decades.

On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration: a European multi-centre evaluation.

INTRODUCTION: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging. MATERIALS AND METHODS: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68-107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I. RESULTS: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12-1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction. CONCLUSION: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.

EFOMP policy statement NO. 19: Dosimetry in nuclear medicine therapy - Molecular radiotherapy.

The European Council Directive 2013/59/Euratom (BSS Directive) includes optimisation of treatment with radiotherapeutic procedures based on patient dosimetry and verification of the absorbed doses delivered. The present policy statement summarises aspects of three directives relating to the therapeutic use of radiopharmaceuticals and medical devices, and outlines the steps needed for implementation of patient dosimetry for radioactive drugs. To support the transition from administrations of fixed activities to personalised treatments based on patient-specific dosimetry, EFOMP presents a number of recommendations including: increased networking between centres and disciplines to support data collection and development of codes-of-practice; resourcing to support an infrastructure that permits routine patient dosimetry; research funding to support investigation into individualised treatments; inter-disciplinary training and education programmes; and support for investigator led clinical trials. Close collaborations between the medical physicist and responsible practitioner are encouraged to develop a similar pathway as is routine for external beam radiotherapy and brachytherapy. EFOMP's policy is to promote the roles and responsibilities of medical physics throughout Europe in the development of molecular radiotherapy to ensure patient benefit. As the BSS directive is adopted throughout Europe, unprecedented opportunities arise to develop informed treatments that will mitigate the risks of under- or over-treatments.

Averaging of absorbed doses: How matter matters.

BACKGROUND: Dosimetry in radionuclide therapy often requires the calculation of average absorbed doses within and between spatial regions, for example, for voxel-based dosimetry methods, for paired organs, or across multiple tumors. Formation of such averages can be made in different ways, starting from different definitions. PURPOSE: The aim of this study is to formally specify different averaging strategies for absorbed doses, and to compare their results when applied to absorbed dose distributions that are non-uniform within and between regions. METHODS: For averaging within regions, two definitions of the average absorbed dose are considered: the simple average over the region (the region average) and the average when weighting by the mass density (density-weighted region average). The latter is shown to follow from the definition of mean absorbed dose according to the ICRU, and to be consistent with the MIRD formalism. For averaging between different spatial regions, three definitions follow: the volume-weighted, the mass-weighted, and the unweighted average. With respect to characterizing non-uniformity, the different average definitions lead to the use of dose-volume histograms (DVHs) (region average), dose-mass histograms (DMHs) (density-weighted region average), and unweighted histograms (unweighted average). Average absorbed doses are calculated for three worked examples, starting from the different definitions. The first, schematic, example concerns the calculation of the average absorbed dose between two regions with different volumes or mass densities. The second, stylized, example concerns voxel-based dosimetry, for which the average absorbed-dose rate within a region is calculated. The geometries studied include three 177 Lu-filled voxelized spheres, where the sphere masses are held constant while the material compositions, densities, and volumes are varied. For comparison, the mean absorbed-dose rates obtained using unit-density sphere S-values are also included. The third example concerns SPECT/CT-based tumor dosimetry for five patients undergoing therapy with 177 Lu-PSMA and six patients undergoing therapy with 177 Lu-DOTA-TATE, for which the average absorbed-dose rates across multiple tumors are calculated. For the second and third examples, analyses also include representations by histograms. RESULTS: Example 1 shows that the average absorbed doses, calculated using different definitions, can differ considerably if the masses and absorbed doses for two regions are markedly different. From example 2 it is seen that the density-weighted region average is stable under different activity and density distributions and is also in line with results using S-values. In contrast, the region average varies as function of the activity distribution. In example 3, the absorbed dose rates for individual tumors differ by (1.1 ± 4.3)% and (-0.1 ± 0.4)% with maximum deviations of +34.4% and -1.4% for 177 Lu-PSMA and 177 Lu-DOTA-TATE, respectively, when calculated as region averages or density-weighted region averages, with largest deviations obtained when the density is non-uniform. The average absorbed doses calculated across all tumors are similar when comparing mass-weighted and volume-weighted averages but these differ substantially from unweighted averages. CONCLUSION: Different strategies for averaging of absorbed doses within and between regions can lead to substantially different absorbed-dose estimates. At reporting of radionuclide therapy dosimetry, it is important to specify the averaging strategy applied.

Relationships between uptake of [68Ga]Ga-DOTA-TATE and absorbed dose in [177Lu]Lu-DOTA-TATE therapy.

BACKGROUND: Somatostatin receptor 68Ga PET imaging is standard for evaluation of a patient's suitability for 177Lu peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The 68Ga PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in 68Ga PET and absorbed doses in 177Lu therapy. METHOD: Eighteen patients underwent [68Ga]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [177Lu]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT-planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The 68Ga activity concentrations per injected activity, SUVs, and normalized SUVs were compared with 177Lu activity concentrations 1 d post-injection and 177Lu absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of 177Lu tumour absorbed doses based on a combination of tumour-specific 68Ga activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored. RESULTS: For normal organs, only spleen showed a significant correlation between the 68Ga activity concentration and 177Lu absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using 68Ga SUVs or normalized SUVs. The relationship between activity uptakes for 68Ga PET and 177Lu SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The 177Lu absorbed dose to tumour could be predicted from the 68Ga activity concentrations with a 95% coverage interval of - 65% to 248%. CONCLUSIONS: On a group level, a high uptake of [68Ga]Ga-DOTA-TATE is associated with high absorbed doses at 177Lu-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity.

Monte Carlo modelling of a compact CZT-based gamma camera with application to 177Lu imaging.

BACKGROUND: Semiconductor gamma-camera systems based on cadmium zinc telluride (CZT) detectors present new challenges due to an energy-response that includes effects of low-energy tailing. In particular, such energy tails produce effects that need to be considered when imaging radionuclides with multiple emissions such as [Formula: see text]. Monte Carlo simulation can be used to investigate the behaviour of such systems and optimise their use, provided that the detector model closely reflects the real physical detector. The aim of this work is to develop a CZT model applicable for simulation of CZT-based gamma cameras. METHODS: The equations describing the charge transport and signal induction are considered in three dimensions and are solved numerically, and the CZT model is then realised by coupling the detector-response to the photon-transport handled by the SIMIND Monte Carlo program. The CZT model is tuned to reproduce experimentally measured energy spectra of a hand-held gamma camera system for multiple radionuclides ([Formula: see text], [Formula: see text] and [Formula: see text]) and parallel-hole collimators (MEGP, LEHR) as well as an uncollimated system. RESULTS: Overall, the model results agree well with measurements across the range of experimental conditions. The applicability of the model is demonstrated by separating energy spectra into components to investigate the interference of high-energy photons on lower energy-windows, where pronounced effects of low-energy tailing for [Formula: see text] are observed. CONCLUSIONS: The developed model provides understanding of the specifics of the camera response and is expected to be helpful for future optimisation of gamma camera applications.

EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands.

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.

EANM dosimetry committee series on standard operational procedures: a unified methodology for 99mTc-MAA pre- and 90Y peri-therapy dosimetry in liver radioembolization with 90Y microspheres.

The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in 90Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient-relative calibration method for activity quantification.The identity of 99mTc albumin macro-aggregates (MAA) and 90Y microsphere biodistribution is also assumed. The large observed discrepancies in some patients between 99mTc-MAA predictions and actual 90Y microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments.Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected 99mTc-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and 90Y TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected 99mTc-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative 90Y bremsstrahlung SPECT can be used if dedicated correction methods are available.The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.

Pituitary Function after High-Dose 177Lu-DOTATATE Therapy and Long-Term Follow-Up.

INTRODUCTION: The pituitary gland has a high expression of somatostatin receptors and is therefore a potential organ at risk for radiation-induced toxicity after 177Lu-DOTATATE treatment. OBJECTIVE: To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based 177Lu-DOTATATE to detect possible late toxicity. METHODS: 68 patients from a phase II clinical trial of dosimetry-based, individualized 177Lu-DOTATATE therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF-1 axis, gonadotropins, and adrenal and thyroid axes were analyzed at baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using box plots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed versus percent change in IGF-1 levels over time. RESULTS: A statistically significant decrease in IGF-1 levels was found (p < 0.005), which correlated with the number of treatment cycles (p = 0.008) and the absorbed radiation dose (p = 0.03). A similar decrease, although non-significant, was seen in gonadotropins in postmenopausal women, while in men there was an increase during the first years after therapy, after which the levels returned to baseline. No change was observed in the adrenal or thyroid axes. CONCLUSIONS: No signs of severe endocrine disorders were detected, although a significant decrease in the GH/IGF-1 axis was found, where dosimetric analyses indicated radiation-induced damage to the pituitary gland as a probable cause.

Characterisation of a hand-held CZT-based gamma camera for 177Lu imaging.

BACKGROUND: Currently, hand-held gamma cameras are being developed for 99mTc imaging, mainly for sentinel lymph node detection. These cameras offer advantages, such as mobility and ease of access, and may be useful also for other applications such as biokinetic studies in animals or for imaging of small, superficial structures in patients. In this work, the suitability of a CZT-based hand-held camera for 177Lu imaging is investigated. The energy response of CZT-based detectors combined with the multiple photon emissions of 177Lu poses new challenges compared to 99mTc imaging, and a thorough camera characterisation is thus warranted. METHODS: Three collimators (LEHR, LEHS, and MEGP) and three energy windows (55 keV, 113 keV, and 208 keV) are investigated. Characterised camera properties include the system spatial resolution, energy resolution, sensitivity, image uniformity, septal penetration, and temperature dependence. Characterisations are made starting from NEMA guidelines when applicable, with adjustments made when required. The applicability of the camera is demonstrated by imaging of a superficially located tumour in a patient undergoing [177 Lu]Lu-DOTA-TATE therapy. RESULTS: Overall, the results are encouraging. Compared to a conventional gamma camera, the hand-held camera generally has a higher sensitivity for a given collimator. For source-collimator distances below 3 cm, the spatial resolution FWHM is within 6 mm for the LEHR and MEGP collimators. Before uniformity correction, the central field-of-view integral uniformity shows best results for the 113-keV window, with values obtained between 11 and 14%. The corresponding values after uniformity correction are within 3%. Effects of septal penetration are observed but are manageable with a proper combination of collimator and energy window setting. Septal penetration and collimator scatter not only affect the 208-keV window but also contribute with counts in lower windows due to energy-tailing effects. The patient study revealed non-uniform uptake patterns in a region that appeared uniform in a conventional gamma camera image. CONCLUSIONS: The results show that the hand-held camera can be used for 177Lu imaging. A 113-keV energy window combined with LEHR or MEGP collimators provides the best image system characteristics.

Analysis of activity uptake, effective half-life and time-integrated activity for low- and high-risk papillary thyroid cancer patients treated with 1.11 GBq and 3.7 GBq of 131I-NaI respectively.

PURPOSE: To analyse the activity uptakes, effective half-lives and time-integrated activities, of relevance for remnant dosimetry, for patients treated for papillary thyroid cancer (PTC) with a different amount of activity of 131I-NaI. METHODS: Fifty patients were included. Of those, 18 patients had low-risk PTC and were treated with 1.11 GBq of 131I-NaI (Group 1), and 32 patients had high-risk PTC and were treated with 3.7 GBq (Group 2). Radioiodine was administered after total thyroidectomy and rhTSH stimulation. Two SPECT/CT scans were performed for each patient to determine the remnant activities and effective half-lives. RESULTS: Significantly higher values (p < 0.05) were obtained for Group 1 for the remnant activity at 7 d (medians 1.4 MBq vs 0.27 MBq), the remnant activity per administered activity at 2 d (0.35% vs 0.09%) and at 7 d (0.13% vs 0.007%), and the effective half-life (93 h vs 40 h). Likewise, the time-integrated activity coefficient was significantly higher for Group 1. The time-integrated activity did not differ significantly between the two groups (p > 0.05). CONCLUSIONS: We found a significant difference in the remnant activity per administered activity, the rate of washout from thyroid remnants, and the time-integrated activity coefficient between low-risk PTC patients treated with 1.11 GBq and high-risk PTC patients treated with 3.7 GBq. On the contrary, there was no such difference in the time-integrated activity. If remnant masses were also not statistically different (reasonable assumption for this monocentric study) no difference in time-integrated activity would imply no difference in remnant absorbed dose, of relevance for treatment efficacy and the risks of stochastic effects.

A method for tumor dosimetry based on hybrid planar-SPECT/CT images and semiautomatic segmentation.

PURPOSE: A hybrid planar-SPECT/CT method for tumor dosimetry in 177 Lu-DOTATATE therapy, applicable to datasets consisting of multiple conjugate-view images and one SPECT/CT, is developed and evaluated. METHODS: The imaging protocol includes conjugate-view imaging at 1, 24, 96, and 168 h post infusion (p.i.) and a SPECT/CT acquisition 24 h p.i. The dosimetry method uses the planar images to estimate the shape of the time-activity concentration curve, which is then rescaled to absolute units using the SPECT-derived activity concentration. The resulting time-integrated activity concentration coefficient (TIACC) is used to calculate the tumor-absorbed dose. Semiautomatic segmentation techniques are applied for tumor delineation in both planar and SPECT images, where the planar image segmentation is accomplished using an active-rays-based technique. The selection of tumors is done by visual inspection of planar and SPECT images and applying a set of criteria concerning the tumor visibility and possible interference from superimposed activity uptakes in the planar images. Five different strategies for determining values from planar regions of interest (ROIs), based on entire or partial ROIs, and with and without background correction, are evaluated. Evaluation is performed against a SPECT/CT-based method on data from six patients where sequential conjugate-view and SPECT/CT imaging have been performed in parallel and against ground truths in Monte Carlo simulated images. The patient data are also used to evaluate the interoperator variability and to assess the validity of the developed criteria for tumor selection. RESULTS: For patient images, the hybrid method produces TIACCs that are on average 6% below those of the SPECT/CT only method, with standard deviations for the relative TIACC differences of 8%-11%. Simulations show that the hybrid and SPECT-based methods estimate the TIACCs to within approximately 10% for tumors larger than around 10 ml, while for smaller tumors, all methods underestimate the TIACCs due to underestimations of the activity concentrations in the SPECT images. The planar image segmentation has a low operator dependence, with a median Dice similarity coefficient of 0.97 between operators. The adopted criteria for tumor selection manage to discriminate the tumors for which the absorbed-dose deviations between the hybrid and SPECT methods are the highest. CONCLUSIONS: The hybrid method is found suitable for studies of tumor-absorbed doses in radionuclide therapy, provided that selection criteria regarding the visibility and overlapping activities in the planar images are applied.

Inter-comparison of quantitative imaging of lutetium-177 (177Lu) in European hospitals.

BACKGROUND: This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources-they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. RESULTS: The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. CONCLUSIONS: A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods.

Feasibility of simplifying renal dosimetry in 177Lu peptide receptor radionuclide therapy.

BACKGROUND: Recently, 177Lu-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done. The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours. As part of a clinical trial on 177Lu-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses. RESULTS: In general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD. CONCLUSIONS: Performing one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.

Variations in the practice of molecular radiotherapy and implementation of dosimetry: results from a European survey.

BACKGROUND: Currently, the implementation of dosimetry in molecular radiotherapy (MRT) is not well investigated, and in view of the Council Directive (2013/59/Euratom), there is a need to understand the current availability of dosimetry-based MRT in clinical practice and research studies. The aim of this study was to assess the current practice of MRT and dosimetry across European countries. METHODS: An electronic questionnaire was distributed to European countries. This addressed 18 explicitly considered therapies, and for each therapy, a similar set of questions were included. Questions covered the number of patients and treatments during 2015, involvement of medical specialties and medical physicists, implementation of absorbed dose planning, post-therapy imaging and dosimetry, and the basis of therapy prescription. RESULTS: Responses were obtained from 26 countries and 208 hospitals, administering in total 42,853 treatments. The most common therapies were 131I-NaI for benign thyroid diseases and thyroid ablation of adults. The involvement of a medical physicist (mean over all 18 therapies) was reported to be either minority or never by 32% of the responders. The percentage of responders that reported that dosimetry was included on an always/majority basis differed between the therapies and showed a median value of 36%. The highest percentages were obtained for 177Lu-PSMA therapy (100%), 90Y microspheres of glass (84%) and resin (82%), 131I-mIBG for neuroblastoma (59%), and 131I-NaI for benign thyroid diseases (54%). The majority of therapies were prescribed based on fixed-activity protocols. The highest number of absorbed-dose based prescriptions were reported for 90Y microsphere treatments in the liver (64% and 96% of responses for resin and glass, respectively), 131I-NaI treatment of benign thyroid diseases (38% of responses), and for 131I-mIBG treatment of neuroblastoma (18% of responses). CONCLUSIONS: There is a wide variation in MRT practice across Europe and for different therapies, including the extent of medical-physicist involvement and the implementation of dosimetry-guided treatments.