Background: Effective dose represents the potential risk to a population of stochastic effects of ionizing radiation (mainly lethal cancer). In recent years, there have been a number of revisions and updates influencing the way to estimate the effective dose. The aim of this work was to recalculate the effective dose values for the 338 different radiopharmaceuticals previously published by the International Commission on Radiological Protection (ICRP).

Method: The new estimations are based on information on the cumulated activities per unit administered activity in various organs and tissues and for the various radiopharmaceuticals obtained from the ICRP publications 53, 80 and 106. The effective dose for adults was calculated using the new ICRP/International Commission on Radiation Units (ICRU) reference voxel phantoms and decay data from the ICRP publication 107. The ICRP human alimentary tract model has also been applied at the recalculations. The effective dose was calculated using the new tissue weighting factors from ICRP publications 103 and the prior factors from ICRP publication 60. The results of the new calculations were compared with the effective dose values published by the ICRP, which were generated with the Medical Internal Radiation Dose (MIRD) adult phantom and the tissue weighting factors from ICRP publication 60.

Results: For 79% of the radiopharmaceuticals, the new calculations gave a lower effective dose per unit administered activity than earlier estimated. As a mean for all radiopharmaceuticals, the effective dose was 25% lower. The use of the new adult computational voxel phantoms has a larger impact on the change of effective doses than the change to new tissue weighting factors.

Conclusion: The use of the new computational voxel phantoms and the new weighting factors has generated new effective dose estimations. These are supposed to result in more realistic estimations of the radiation risk to a population undergoing nuclear medicine investigations than hitherto available values.

Purpose

Over recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.

Methods

In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following ¹⁷⁷Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.

Results

Differences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.

Conclusion

This study indicates that for ¹⁷⁷Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.

Background Whole-body bone scintigraphy is a clinically useful non-invasive and highly sensitive imaging method enabling detection of metabolic changes at an early stage of disease, often earlier than with conventional radiologic procedures. Bone scintigraphy is one of the most common nuclear medicine methods used worldwide. Therefore, it is important that the examination is implemented and performed in an optimal manner giving the patient added value in the subsequent care process. The aim of this national multicentre survey was to investigate Swedish nuclear medicine departments compliance with European practice guidelines for bone scintigraphy. In addition, the effect of image acquisition parameters on the ability to detect metabolic lesions was investigated. Methods Twenty-five hospital sites participated in the study. The SIMIND Monte Carlo (MC) simulation and the XCAT phantom were used to simulate ten fictive patient cases with increased metabolic activity distributed at ten different locations in the skeleton. The intensity of the metabolic activity was set into six different levels. Individual simulations were performed for each site, corresponding to their specific camera system and acquisition parameters. Simulated image data sets were then sent to each site and were visually evaluated in terms of if there was one or several locations with increased metabolic activity relative to normal activity. Result There is a high compliance in Sweden with the EANM guidelines regarding image acquisition parameters for whole-body bone scintigraphy. However, up to 40% of the participating sites acquire lower count density in the images than recommended. Despite this, the image quality was adequate to maintain a stable detection level. None of the hospital sites or individual responders deviated according to the statistical analysis. There is a need for at least 2.5 times metabolic activity compared to normal for a lesion to be detected. Conclusion The imaging process is well harmonized throughout the country and there is a high compliance with the EANM guidelines. There is a need for at least 2.5 times the normal metabolic activity for a lesion to be detected as abnormal.

BACKGROUND: The aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners.

METHODS: 35 subjects underwent a dynamic (11)C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic (15)O-water PET and (11)C-acetate PET scans on a GE Discovery-ST PET/CT (scanner II). The left ventricular (LV)-aortic time-activity curve (TAC) was extracted automatically from PET data using cluster analysis. The first-pass peak was isolated by automatic extrapolation of the downslope of the TAC. FSV was calculated as the injected dose divided by the product of heart rate and the area under the curve of the first-pass peak. Gold standard FSV was measured using phase-contrast cardiovascular magnetic resonance (CMR).

RESULTS: FSVPET correlated highly with FSVCMR (r = 0.87, slope = 0.90 for scanner I, r = 0.87, slope = 1.65, and r = 0.85, slope = 1.69 for scanner II for (15)O-water and (11)C-acetate, respectively) although a systematic bias was observed for both scanners (p < 0.001 for all). FSV based on (11)C-acetate and (15)O-water correlated highly (r = 0.99, slope = 1.03) with no significant difference between FSV estimates (p = 0.14).

CONCLUSIONS: FSV can be obtained automatically using dynamic PET/CT and cluster analysis. Results are almost identical for (11)C-acetate and (15)O-water. A scanner-dependent bias was observed, and a scanner calibration factor is required for multi-scanner studies. Generalization of the method to other tracers and scanners requires further validation.

Background: The Otsu method and the Chan-Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity.Methods: A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m (Tc-99m). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu's threshold selection method and an adaptation of the Chan-Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient.Results: Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan-Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value &lt; 0.01).Conclusions: The investigations indicate that the Chan-Vese model performs better and is slightly more robust, while being more challenging to implement and use clinically. There is a trade-off between performance and user-friendliness.

BACKGROUND: The Otsu method and the Chan-Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity.

METHODS: A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m ([Formula: see text]Tc). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu's threshold selection method and an adaptation of the Chan-Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient.

RESULTS: Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan-Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value [Formula: see text]).

CONCLUSIONS: The investigations indicate that the Chan-Vese model performs better and is slightly more robust, while being more challenging to implement and use clinically. There is a trade-off between performance and user-friendliness.

BACKGROUND: The use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46-74 years) with known or suspected coronary artery disease underwent (15)O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values.

RESULTS: Stress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00.

CONCLUSIONS: PET-MR-based MBF values correlated well with PET-CT-based MBF values and the parametric PET-MR images were excellent. TOF and reconstruction settings had little impact on MBF values.

BACKGROUND: Block-sequential regularized expectation maximization (BSREM) is a fully convergent iterative image reconstruction algorithm. We hypothesize that tracers with different distribution patterns will result in different optimal settings for the BSREM algorithm. The aim of this study was to evaluate the image quality with variations in the applied β-value and acquisition time for three positron emission tomography (PET) tracers. NEMA image quality phantom measurements and clinical whole-body digital time-of-flight (TOF) PET/computed tomography (CT) examinations with ⁶⁸Ga-DOTATOC (n = 13), ¹⁸F-fluoride (n = 10), and ¹¹C-acetate (n = 13) were included. Each scan was reconstructed using BSREM with β-values of 133, 267, 400, and 533, and ordered subsets expectation maximization (OSEM; 3 iterations, 16 subsets, and 5-mm Gaussian post-processing filter). Both reconstruction methods included TOF and point spread function (PSF) recovery. Quantitative measures of noise, signal-to-noise ratio (SNR), and signal-to-background ratio (SBR) were analysed for various acquisition times per bed position (bp).

RESULTS: The highest β-value resulted in the lowest level of noise, which in turn resulted in the highest SNR and lowest SBR. Noise levels equal to or lower than those of OSEM were found with β-values equal to or higher than 400, 533, and 267 for ⁶⁸Ga-DOTATOC, ¹⁸F-fluoride, and ¹¹C-acetate, respectively. The specified β-ranges resulted in increased SNR at a minimum of 25% (P < 0.0001) and SBR at a maximum of 23% (P < 0.0001) as compared to OSEM. At a reduced acquisition time by 25% for ⁶⁸Ga-DOTATOC and ¹⁸F-fluoride, and 67% for ¹¹C-acetate, BSREM with β-values equal to or higher than 533 resulted in noise equal to or lower than that of OSEM at full acquisition duration (2 min/bp for ⁶⁸Ga-DOTATOC and ¹⁸F-fluoride, 3 min/bp for ¹¹C-acetate). The reduced acquisition time with β 533 resulted in increased SNR (16-26%, P < 0.003) and SBR (6-18%, P < 0.0001 (P = 0.07 for ¹¹C-acetate)) compared to the full acquisition OSEM.

CONCLUSIONS: Within tracer-specific ranges of β-values, BSREM reconstruction resulted in increased SNR and SBR with respect to conventional OSEM reconstruction. Similar SNR, SBR, and noise levels could be attained with BSREM at relatively shorter acquisition times or, alternatively, lower administered dosages, compared to those attained with OSEM.

BACKGROUND: Quantitative measurement of myocardial blood flow (MBF) is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD). (15)O-water positron emission tomography (PET) is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV) volumes and ejection fraction (EF) is not possible from standard (15)O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B) (15)O-water images and from first pass (FP) images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated (15)O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV) and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI.

RESULTS: Using V B images, high correlations between PET and MRI ESV (r = 0.89, p < 0.001), EDV (r = 0.85, p < 0.001), SV (r = 0.74, p = 0.006) and LVEF (r = 0.72, p = 0.008) were found for the volume-based method. Correlations for FP images were slightly, but not significantly, lower than those for V B images when compared to MRI. Surface- and count-based methods showed no significant difference compared with the volume-based correlations with MRI. The volume-based method showed the best agreement with MRI with no significant difference on average for EDV and LVEF but with an overestimation of values for ESV (14%, p = 0.005) and SV (18%, p = 0.004) when using V B images. Using FP images, none of the parameters showed a significant difference from MRI. Inter-operator repeatability was excellent for all parameters (ICC > 0.86, p < 0.001).

CONCLUSION: Calculation of LV volumes and LVEF from dynamic (15)O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.

Background: 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.

Methods: Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.

Results: [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).

Conclusion: The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

Purpose

Fractionated peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE is increasingly applied as an effective treatment for patients with disseminated neuroendocrine tumors. In parallel to dose planning before external beam radiation therapy, dosimetry is also needed to optimize PRRT to the individual patient. Accordingly, absorbed doses to organs at risk need to be calculated during PRRT, based on serial measurements of radioactivity distribution utilizing SPECT/CT. The dosimetry should be based on as few measurements as possible, while still retaining reliable results. The main aim of the present work was to calculate the fractional contribution of the extrapolations of the curve fits for the absorbed dose calculations to the kidneys. The secondary aim was to study agreement between absorbed dose (AD) and the effective half-life (t_eff) for the kidneys, estimated by means of measurements at one or two time points, in comparison to our current method employing three time points.

Methods

In 777 patients with disseminated neuroendocrine tumors undergoing PRRT, SPECT/CT over the abdomen was acquired at 1, 4, and 7 days after ¹⁷⁷Lu-DOTATATE infusion. The absorbed dose to the kidneys was calculated from SPECT/CT radioactivity distribution data, and the t_eff and fractional contributions of the extrapolations were estimated, utilizing data from one, two, and three time points, respectively.

Results

The fractional contributions from extrapolations before day 1 measurement and after day 7 measurement were approximately 26% and 11%, respectively. The mean differences in absorbed dose, based on one, two, and three time points were small, but with high method dependence for individual patients. The differences in estimated t_eff were small when it was based on measurements at days 1 and 7, but high for days 1 and 4 time points.

Conclusion

When assessing simplifications of methods for calculation of the absorbed dose to the kidneys, it was of the uttermost importance to incorporate the fractional contribution for the extrapolations included in the reference method. Measurements at an early and a late time point were found most important. An intermediate measurement contributes with an idea of the goodness of the fit.

BACKGROUND: Radionuclide therapy can be individualized by performing dosimetry. To determine absorbed organ doses in (177)Lu-DOTATATE therapy, three methods based on activity concentrations are currently in use: the small volume of interest (sVOI) method, and two methods based on large VOIs either on anatomical CT (aVOI) or on thresholds on functional images (tVOI). The main aim of the present work was to validate the sVOI in comparison to the other two methods regarding agreement and time efficiency. Secondary aims were to investigate inter-observer variability for the sVOI and the change of functional organ volumes following therapy.

METHODS: Thirty patients diagnosed with neuroendocrine tumours undergoing therapy with (177)Lu-DOTATATE were included. Each patient underwent three SPECT/CT scans at 1, 4 and 7 days after the treatment. Three independent observers calculated absorbed doses to the right and left kidney and the spleen using sVOI and one observer used aVOI. For tVOI, the absorbed doses were calculated based on automatically drawn isocontours around the organs at different thresholds (42, 50, 60 and 70 %). The inter-observer difference between the calculated absorbed doses for sVOI was calculated, and the differences between the three methods were computed. Ratios of organ volumes acquired at days 1, 4 and 7 versus the volume at day 1 were calculated for the tVOI method.

RESULTS: The differences in results of the absorbed dose calculations using all the sVOI and tVOI were small (<5 %). Absorbed dose calculations using aVOI differed slightly more from these results but were still below 10 %. The differences between the three dose calculation methods varied between <5 and 10 %. The organ volumes derived from the tVOI were independent of time for the spleen while they decreased with time for the kidneys. The fastest analysis was performed with the sVOI method.

CONCLUSIONS: All three dose calculation methods rendered comparable results with small inter-observer differences for sVOI. Unlike the spleen, the functional volume of the kidneys decreased over time during therapy, which suggests that the absorbed dose calculation for the kidneys on activity concentrations should be performed for each time point. The sVOI is the preferred method for calculating absorbed doses in solid organs.

Background

Prediction of [¹⁷⁷Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [⁶⁸Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [¹⁷⁷Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [¹⁷⁷Lu]Lu-HA-DOTATATE and [⁶⁸Ga]Ga-HA-DOTATATE were assessed and subsequently [¹⁷⁷Lu]Lu-HA-DOTATATE was predicted based on [⁶⁸Ga]Ga-HA-DOTATATE imaging.

Methods

A semi-physiological nonlinear mixed-effects model was developed for [⁶⁸Ga]Ga-HA-DOTATATE and [¹⁷⁷Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment). Model parameters were fixed based on a previously developed physiologically based pharmacokinetic model for [⁶⁸Ga]Ga-HA-DOTATATE. For [¹⁷⁷Lu]Lu-HA-DOTATATE, PK parameters were based on literature values or estimated based on scan data (four time points post-injection) from nine patients. Finally, individual [¹⁷⁷Lu]Lu-HA-DOTATATE uptake into tumors and kidneys was predicted based on individual [⁶⁸Ga]Ga-HA-DOTATATE scan data using Bayesian estimates. Predictions were evaluated compared to observed data using a relative prediction error (RPE) for both area under the curve (AUC) and absorbed dose. Lastly, to assess the predictive value of diagnostic imaging to predict therapeutic exposure, individual prediction RPEs (using Bayesian estimation) were compared to those from population predictions (using the population model).

Results

Population uptake rate parameters for spleen, kidney and tumors differed by a 0.29-fold (15% relative standard error (RSE)), 0.49-fold (15% RSE) and 1.43-fold (14% RSE), respectively, for [¹⁷⁷Lu]Lu-HA-DOTATATE compared to [⁶⁸Ga]Ga-HA-DOTATATE. Model predictions adequately described observed data in kidney and tumors for both peptides (based on visual inspection of goodness-of-fit plots). Individual predictions of tumor uptake were better (RPE AUC –40 to 28%) compared to kidney predictions (RPE AUC –53 to 41%). Absorbed dose predictions were less predictive for both tumor and kidneys (RPE tumor and kidney –51 to 44% and –58 to 82%, respectively). For most patients, [¹⁷⁷Lu]Lu-HA-DOTATATE tumor accumulation predictions based on individual PK parameters estimated from diagnostic imaging outperformed predictions based on population parameters.

Conclusion

Our semi-physiological PK model indicated clear differences in PK parameters for [⁶⁸Ga]Ga-HA-DOTATATE and [¹⁷⁷Lu]Lu-HA-DOTATATE. Diagnostic images provided additional information to individually predict [¹⁷⁷Lu]Lu-HA-DOTATATE tumor uptake compared to using a population approach. In addition, individual predictions indicated that many aspects, apart from PK differences, play a part in predicting [¹⁷⁷Lu]Lu-HA-DOTATATE distribution.

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 I-131-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 Lu-177-PSMA therapy (100%), Y-90 microspheres of glass (84%) and resin (82%), I-131-mIBG for neuroblastoma (59%), and I-131-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 Y-90 microsphere treatments in the liver (64% and 96% of responses for resin and glass, respectively), I-131-NaI treatment of benign thyroid diseases (38% of responses), and for I-131-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.

Background: MRI does not offer a direct method to obtain attenuation correction maps as its predecessors (stand-alone PET and PET/CT), and bone visualisation is particularly challenging. Recently, zero-echo-time (ZTE) was suggested for MR-based attenuation correction (AC). The aim of this work was to evaluate ZTE- and atlas-AC by comparison to ⁶⁸Ge-transmission scan-based AC.

Nine patients underwent brain PET/MR and stand-alone PET scanning using the dopamine transporter ligand ¹¹C-PE2I. For each of them, two AC maps were obtained from the MR images: an atlas-based, obtained from T1-weighted LAVA-FLEX imaging with cortical bone inserted using a CT-based atlas, and an AC map generated from proton-density-weighted ZTE images. Stand-alone PET ⁶⁸Ge-transmission AC map was used as gold standard. PET images were reconstructed using the three AC methods and standardised uptake value (SUV) values for the striatal, limbic and cortical regions, as well as the cerebellum (VOIs) were compared. SUV ratio (SUVR) values normalised for the cerebellum were also assessed. Bias, precision and agreement were calculated; statistical significance was evaluated using Wilcoxon matched-pairs signed-rank test.

Results: Both ZTE- and atlas-AC showed a similar bias of 6–8% in SUV values across the regions. Correlation coefficients with ⁶⁸Ge-AC were consistently high for ZTE-AC (r 0.99 for all regions), whereas they were lower for atlas-AC, varying from 0.99 in the striatum to 0.88 in the posterior cortical regions. SUVR showed an overall bias of 2.9 and 0.5% for atlas-AC and ZTE-AC, respectively. Correlations with ⁶⁸Ge-AC were higher for ZTE-AC, varying from 0.99 in the striatum to 0.96 in the limbic regions, compared to atlas-AC (0.99 striatum to 0.77 posterior cortex).

Conclusions: Absolute SUV values showed less variability for ZTE-AC than for atlas-AC when compared to ⁶⁸Ge-AC, but bias was similar for both methods. This bias is largely caused by higher linear attenuation coefficients in atlas- and ZTE-AC image compared to ⁶⁸Ge-images. For SUVR, bias was lower when using ZTE-AC than for atlas-AC. ZTE-AC shows to be a more robust technique than atlas-AC in terms of both intra- and inter-patient variability.

BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.

METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [¹¹C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The ⁶⁸Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R₁) images and binding potential (BP_ND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [¹¹C]PE2I BP_ND and R₁ estimates, and [¹¹C]PE2I time-activity curves. BP_ND was examined for striatal regions and R₁ in clusters of regions across the brain.

RESULTS: For BP_ND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R₁ estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R₁ and BP_ND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.

CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a ⁶⁸Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [¹¹C]PE2I PET analysis with use of kinetic modelling.

The European directive on basic safety standards (Council directive 2013/59 Euratom) mandates dosimetry-based treatment planning for radiopharmaceutical therapies. The directive comes into operation February 2018, and the aim of a report produced by the Internal Dosimetry Task Force of the European Association of Nuclear Medicine is to address this aspect of the directive. A summary of the report is presented. A brief review of five of the most common therapy procedures is included in the current text, focused on the potential to perform patient-specific dosimetry. In the full report, 11 different therapeutic procedures are included, allowing additional considerations of effectiveness, references to specific literature on quantitative imaging and dosimetry, and existing evidence for absorbed dose-effect correlations for each treatment. Individualized treatment planning with tracer diagnostics and verification of the absorbed doses delivered following therapy is found to be scientifically feasible for almost all procedures investigated, using quantitative imaging and/or external monitoring. Translation of this directive into clinical practice will have significant implications for resource requirements. Molecular radiotherapy is undergoing a significant expansion, and the groundwork for dosimetry-based treatment planning is already in place. The mandated individualization is likely to improve the effectiveness of the treatments, although must be adequately resourced.

Background: Myocardial perfusion scintigraphy (MPS) is a clinically useful noninvasive imaging modality for diagnosing patients with suspected coronary artery disease. By utilizing gated MPS, the end diastolic volume (EDV) and end systolic volume (ESV) can be measured and the ejection fraction (EF) calculated, which gives incremental prognostic value compared with assessment of perfusion only. The aim of this study was to evaluate the inter-departmental variability of EF, ESV, and EDV during gated MPS in Sweden.

Methods: Seventeen departments were included in the study. The SIMIND Monte Carlo (MC) program together with the XCAT phantom was used to simulate three patient cases with different EDV, ESV, and EF. Individual simulations were performed for each department, corresponding to their specific method of performing MPS. Images were then sent to each department and were evaluated according to clinical routine. EDV, ESV, and EF were reported back.

Results: There was a large underestimation of EDV and ESV for all three cases. Mean underestimation for EDV varied between 26% and 52% and for ESV between 15% and 60%. EF was more accurately measured, but mean bias still varied between an underestimation of 24% to an overestimation of 14%. In general, the intra-departmental variability for EDV, ESV, and EF was small, whereas inter-departmental variability was larger.

Conclusions: Left ventricular volumes were generally underestimated, whereas EF was more accurately estimated. There was, however, large inter-departmental variability.

Background: Attenuation correction of PET/MRI is a remaining problem for whole-body PET/MRI. The statistical decomposition algorithm (SDA) is a probabilistic atlas-based method that calculates synthetic CTs from T2-weighted MRI scans. In this study, we evaluated the application of SDA for attenuation correction of PET images in the pelvic region.

Materials and method: Twelve patients were retrospectively selected from an ongoing prostate cancer research study. The patients had same-day scans of [11C]acetate PET/MRI and CT. The CT images were non-rigidly registered to the PET/MRI geometry, and PET images were reconstructed with attenuation correction employing CT, SDA-generated CT, and the built-in Dixon sequence-based method of the scanner. The PET images reconstructed using CT-based attenuation correction were used as ground truth.

Results: The mean whole-image PET uptake error was reduced from - 5.4% for Dixon-PET to - 0.9% for SDA-PET. The prostate standardized uptake value (SUV) quantification error was significantly reduced from - 5.6% for Dixon-PET to - 2.3% for SDA-PET.

Conclusion: Attenuation correction with SDA improves quantification of PET/MR images in the pelvic region compared to the Dixon-based method.

Background: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic O-15-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide.

Results: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R-2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% +/- and a coefficient of variation (CoV) of 7.3%.

Conclusion: Our results show promising results that a robust IDIF can be produced for dynamic O-15-water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with O-15-water feasible.

Background: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic ¹⁵O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide.

Results: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R² values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%.

Conclusion: Our results show promising results that a robust IDIF can be produced for dynamic ¹⁵O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with ¹⁵O–water feasible.