Risk of treatment-altering haematological toxicity and its dependence on bone marrow doses in peptide receptor radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy is effective in treating neuroendocrine tumours, but treatment may be limited by kidney and bone marrow toxicity. In this work, the absorbed dose burden to the bone marrow was estimated using image-based dosimetry and its potential use for predicting treatment-altering toxicity was studied. Peripheral blood samples taken before and after 229 treatments with 177Lu-DOTATATE in 59 patients were studied. In connection to the treatments, a total of 940 blood sample occasions provided data on white blood cell, neutrophil granulocyte, platelet, erythrocyte and haemoglobin concentrations. SPECT/CT image data were collected at two or three time points after each treatment. Absorbed doses to bone marrow were calculated from the activity concentration in a metastasis-free lumbar vertebra. The rate of delayed and aborted treatments was analysed based on medical records. RESULTS: The average absorbed dose to the bone marrow was 0.42 Gy (median 0.33 Gy, SD 0.27 Gy) per treatment. Dose-response relationships between white blood cells, neutrophil granulocytes and haemoglobin concentrations were observed, most prominently at 31-45 days after each treatment. The correlations were stronger in patients with skeletal metastases. The rates of haematological toxicity-related delays and aborted treatments were 6% and 12%, respectively. None of the studied bone marrow dosimetric parameters could clearly predict treatment-related toxicity. However, patients with skeletal metastases had higher risk of treatment-altering toxicity (odds ratio = 6.0). CONCLUSIONS: Treatment-altering haematological toxicity in peptide receptor radionuclide therapy is relatively rare and appears difficult to fully predict from post-therapeutic image-based dosimetry. However, for patients with skeletal metastases, the haematological dose-response relationships are stronger. Future studies may focus on this patient group, to further investigate the usefulness of dosimetry in predicting decreases in blood values.

Influence of different time framings, reconstruction algorithms and post-processing methods on the quantification of myocardial blood flow from 13 N-NH3 PET images.

BACKGROUND: The aim was to investigate to what extent the quantification of myocardial blood flow (MBF) from dynamic 13 N-NH3 positron emission tomography (PET) images is affected by time frame schemes, time-of-flight (ToF), reconstruction algorithms, blood pool volume of interest (VOI) locations and compartment models in patients with suspected chronic coronary syndrome. METHODS: A standard MBF value was determined from 25 patients' rest/stress 13 N-NH3 PET/CT images reconstructed with ordered subset expectation maximization (OSEM), 5 s time frame for the first frames without ToF, subsequently analyzed using a basal VOI and the deGrado compartment model. MBFs calculated using 2 or 10 s for the first frames, ToF, block-sequential regularized expectation maximization (BSREM), apical or large VOI, Hutchins or Krivokapich compartment models were compared to MBFstandard in Bland-Altman plots (bias ± SD). RESULTS: Good agreement in global rest/stress MBF (mL/min/g) was found when changing the time frame scheme or reconstruction algorithm (MBFstandard vs. MBF2s : -0.02 ± 0.06; MBF10s : 0.01 ± 0.07; MBFBSREM : 0.01 ± 0.07), while a lower level of agreement was found when altering the other factors (MBFstandard vs. MBFToF : -0.07 ± 0.10; MBFapical VOI : -0.27 ± 0.25; MBFlarge VOI : -0.11 ± 0.10; MBFHutchins : -0.08 ± 0.10; MBFKrivokapich : -0.47 ± 0.50). CONCLUSIONS: Quantification of MBF from 13 N-NH3 PET images is more affected by choice of compartment models, ToF and blood pool VOIs than by different time frame schemes and reconstruction algorithms.

Traceable calibration with 177Lu and comparison of activity meters at hospitals in Norway and Sweden.

INTRODUCTION: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard. METHODS: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe. RESULTS: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %. CONCLUSION: The activity of 177Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.

Monte Carlo investigation of PET [68Ga]Ga-DOTA-TOC activity-administration protocols for consistent image quality.

One example of a PET exam that suffers from noise problems is [68Ga]Ga-DOTA-TOC, where patients are generally administered between 100 and 200 MBq [68Ga]Ga-DOTA-TOC, irrespective of size. However, a fixed activity can result in low signal-to-noise ratios (SNRs) in larger patients. This study aimed to evaluate the impact on image quality with respect to injected activity and patient habitus through Monte Carlo (MC) simulation. Eight anthropomorphic computer phantoms with body mass indices (BMIs) between 19 kg/m2 and 38 kg/m2 and tumours distributed in the liver were simulated using the MC software Gate v8.2 with an activity distribution defined according to [68Ga]Ga-DOTA-TOC standardised uptake values. Three activity-administration protocols were simulated: (i) with a fixed activity of 100 MBq, (ii) with the activity scaled by 2 MBq/kg, and (iii) with the activity scaled by a body size-dependent power-function based on the SNR obtained with (ii). BMI, weight, body surface area, and abdominal circumference were evaluated body size parameters. Images were reconstructed with the CASToR software and evaluated for background SNR and lesion contrast-to-noise ratio (CNR). Large SNR variabilities were obtained with protocols (i) and (ii), while (iii) generated good consistency. Several tumours failed to reach a CNR of 5 for large phantoms with protocol (i), but the CNR was generally improved by (ii) and (iii). An activity scaled by patient habitus generate better image quality consistency, which increases the likelihood that patients receive a similar standard of care.

Diagnostic accuracy for CZT gamma camera compared to conventional gamma camera technique with myocardial perfusion single-photon emission computed tomography: Assessment of myocardial infarction and function.

BACKGROUND: The solid-state cadmium-zinc-telluride (CZT) gamma camera for myocardial perfusion single-photon emission computed tomography (MPS) has theoretical advantages compared to the conventional gamma camera technique. This includes more sensitive detectors and better energy resolution. We aimed to explore the diagnostic performance of gated MPS with a CZT gamma camera compared to a conventional gamma camera for detection of myocardial infarct (MI) and assessment of left ventricular (LV) volumes and ejection fraction (LVEF), using cardiac magnetic resonance (CMR) as the reference method. METHODS: Seventy-three patients (26% female) with known or suspected chronic coronary syndrome were examined with gated MPS using both a CZT gamma camera and a conventional gamma camera as well as with CMR. Presence and extent of MI on MPS and late gadolinium enhancement (LGE) CMR was evaluated. For LV volumes, LVEF and LV mass, gated MPS images and cine CMR images were evaluated. RESULTS: MI was found in 42 patients on CMR. The overall sensitivity, specificity, positive and negative predictive values for the CZT and the conventional gamma camera were the same (67%, 100%, 100% and 69%). For infarct size > 3% on CMR, the sensitivity was 82% for the CZT and 73% for the conventional gamma camera, respectively. LV volumes were significantly underestimated by MPS compared to CMR (P ≤ .002 for all measures). The underestimation was slightly less pronounced for the CZT compared to the conventional gamma camera (2-10 mL, P ≤ .03 for all measures). For LVEF, however, accuracy was high for both gamma cameras. CONCLUSION: Differences between a CZT and a conventional gamma camera for detection of MI and assessment of LV volumes and LVEF are small and do not appear to be clinically significant.

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.

Simplified dosimetry for kidneys and tumors in 177Lu-labeled peptide receptor radionuclide therapy.

PURPOSE: To evaluate if satisfactory post-therapeutic image-based dosimetry can be achieved for Lu-177-DOTATATE treatments using a reduced number of image acquisitions to improve patient comfort and reduce economical costs. METHODS: 39 patients who underwent 147 treatment cycles of Lu-177-DOTATATE for neuroendocrine tumors were included in the study. A total of 291 and 284 absorbed doses were calculated to kidneys and tumors, respectively. Single-point dosimetry was performed using one SPECT/CT image acquired at 1 d or 7 d post-treatment using a fixed effective half-life (Teff) or using a patient-specific Teff determined for the initial cycle. Also, dose-per-activity values, (D/A)1, were determined from the first cycle and used to calculate doses for subsequent cycles. All absorbed doses were evaluated against "true" doses calculated using both the 1 d and 7 d images. The relation between tumor grade and absorbed doses was also investigated. All dosimetry was performed on SPECT images. RESULTS: Absorbed doses to kidneys were most accurate when single-point dosimetry was performed using 1 d images with median ratios in relation to "true" doses in total dose of 1.00 (IQR: 0.97-1.03) when using fixed Teff and 1.01 (IQR: 0.98-1.04) when using Teff from the initial cycle. Calculations based on the 7 d image were most accurate for tumors with corresponding ratios in total absorbed dose of 0.98 (IQR: 0.96-1.00) and 1.00 (IQR: 0.99-1.01) when using a fixed Teff or Teff from the first cycle, respectively. The (D/A)1 approach performed worse, as 2 of 77 total absorbed doses to the kidneys deviated with > 30%, and tumor-absorbed doses were increasingly overestimated with every cycle. Absorbed doses, Teff and 1 d uptake were higher for G1 tumors than G2 tumors. CONCLUSION: Dosimetry can be performed with satisfactory accuracy when using single SPECT/CT images acquired at 1 d for kidneys or at 7 d for tumors.

Validation of a computational chain from PET Monte Carlo simulations to reconstructed images.

The study aimed to create a pipeline from Monte Carlo simulated projections of a Gate PET system to reconstructed images. The PET system was modelled after the GE Discovery MI (DMI) PET/CT, and the simulated projections were reconstructed with the stand-alone reconstruction software CASToR. Attenuation correction, normalisation calibration, random estimation, and scatter estimation for the simulations were computed with in-house programs. The pipeline was compared in both projection and image space with data acquired on a clinical DMI and reconstructed with GE's off-line PET reconstruction software (PET Toolbox) and CASToR. The simulated and measured data were compared for the number of prompt coincidences, scatter fraction, contrast recovery coefficient (CRC), signal-to-noise ratio (SNR), background variability, residual lung error, and image profiles. A slight discrepancy was noted in the projection space, but good agreements were generally achieved in image space between simulated and measured data. The CRC was found to be 81 % for Gate - CASToR, 84 % for GE - CASToR, and 84 % for GE - PET Toolbox for the largest sphere of the NEMA image quality (IQ) phantom, and the SNR was found to be 98 for Gate - CASToR, 91 for GE - CASToR, and 93 for GE - PET Toolbox. Profiles drawn over the spheres for the NEMA IQ phantom and the Data Spectrum (DS) phantom show a good match between measurement and simulation. The results indicate feasibility to utilise the pipeline as a tool for off-line simulation-based studies. A complete pipeline introduces possibilities to study the impact of single parameters in the whole chain from simulation to reconstructed images.

227Th-Labeled Anti-CD22 Antibody (BAY 1862864) in Relapsed/Refractory CD22-Positive Non-Hodgkin Lymphoma: A First-in-Human, Phase I Study.

Background: BAY 1862864 is an α-particle emitting 227Th-labeled CD22-targeting antibody. This first-in-human dose-escalation phase I study evaluated BAY 1862864 in patients with CD22-positive relapsed/refractory B cell non-Hodgkin lymphoma (R/R-NHL). Materials and Methods: BAY 1862864 intravenous injections were administered at the starting 227Th radioactivity dose of 1.5 MBq (2 or 10 mg antibody), and the radioactivity dose escalated in ∼1.5 MBq increments (10 mg antibody) until the maximum tolerated dose (MTD) was reported. The primary objective was to determine the safety, tolerability, and MTD. Results: Twenty-one patients received BAY 1862864. Two dose-limiting toxicities (grade 3 febrile neutropenia and grade 4 thrombocytopenia) were reported in one patient in the 4.6 MBq (10 mg antibody) cohort. The MTD was not reached. Ten (48%) patients reported grade ≥3 treatment-emergent adverse events, with the most common being neutropenia, thrombocytopenia, and leukopenia, each occurring in 3 (14%) patients. Pharmacokinetics demonstrated the dose proportionality and stability of BAY 1862864 in the blood. The objective response rate (ORR) was 25% (5/21 patients) according to the LUGANO 2014 criteria, including 1 complete and 4 partial responses. The ORR was 11% (1/9) and 30% (3/10) in patients with relapsed high- and low-grade lymphomas, respectively. Conclusions: BAY 1862864 was safe and tolerated in patients with R/R-NHL. Clinical Trial Registration numbers: NCT02581878 and EudraCT 2014-004140-36.

EANM position paper on article 56 of the Council Directive 2013/59/Euratom (basic safety standards) for nuclear medicine therapy.

The EC Directive 2013/59/Euratom states in article 56 that exposures of target volumes in nuclear medicine treatments shall be individually planned and their delivery appropriately verified. The Directive also mentions that medical physics experts should always be appropriately involved in those treatments. Although it is obvious that, in nuclear medicine practice, every nuclear medicine physician and physicist should follow national rules and legislation, the EANM considered it necessary to provide guidance on how to interpret the Directive statements for nuclear medicine treatments.For this purpose, the EANM proposes to distinguish three levels in compliance to the optimization principle in the directive, inspired by the indication of levels in prescribing, recording and reporting of absorbed doses after radiotherapy defined by the International Commission on Radiation Units and Measurements (ICRU): Most nuclear medicine treatments currently applied in Europe are standardized. The minimum requirement for those treatments is ICRU level 1 ("activity-based prescription and patient-averaged dosimetry"), which is defined by administering the activity within 10% of the intended activity, typically according to the package insert or to the respective EANM guidelines, followed by verification of the therapy delivery, if applicable. Non-standardized treatments are essentially those in developmental phase or approved radiopharmaceuticals being used off-label with significantly (> 25% more than in the label) higher activities. These treatments should comply with ICRU level 2 ("activity-based prescription and patient-specific dosimetry"), which implies recording and reporting of the absorbed dose to organs at risk and optionally the absorbed dose to treatment regions. The EANM strongly encourages to foster research that eventually leads to treatment planning according to ICRU level 3 ("dosimetry-guided patient-specific prescription and verification"), whenever possible and relevant. Evidence for superiority of therapy prescription on basis of patient-specific dosimetry has not been obtained. However, the authors believe that a better understanding of therapy dosimetry, i.e. how much and where the energy is delivered, and radiobiology, i.e. radiation-related processes in tissues, are keys to the long-term improvement of our treatments.

Appropriate coronary revascularization can be accomplished if myocardial perfusion is quantified by positron emission tomography prior to treatment decision.

BACKGROUND: Many patients undergo percutaneous coronary intervention (PCI) without the use of non-invasive stress testing prior to treatment. The aim of this study was to determine the potential added value of guiding revascularization by quantitative assessment of myocardial perfusion prior to intervention. METHODS AND RESULTS: Thirty-three patients (10 females) with suspected or established CAD who had been referred for a clinical coronary angiography (CA) with possibility for PCI were included. Adenosine stress and rest 13N-NH3 PET, cardiac magnetic resonance (CMR), and cardiopulmonary exercise test were performed 4 ± 3 weeks before and 5 ± 1 months after CA. The angiographer was blinded to the PET and CMR results. Myocardial flow reserve (MFR) < 2.0 by PET was considered abnormal. A PCI was performed in 19/33 patients. In 41% (11/27) of the revascularized vessel territories, a normal regional MFR was found prior to the PCI and no improvement in MFR was found at follow-up (P = 0.9). However, vessel territories with regional MFR < 2.0 at baseline improved significantly after PCI (P = 0.003). Of the 14 patients not undergoing PCI, four had MFR < 2.0 in one or more coronary territories. CONCLUSION: Assessment of quantitative myocardial perfusion prior to revascularization could lead to more appropriate use of CA when managing patients with stable CAD.

Feasibility of Thorium-227/Radium-223 Gamma-Camera Imaging During Radionuclide Therapy.

Thorium-227 (227Th) is a long-lived (T1/2 = 18.7 d) α-emitter that has emerged as candidate for radioimmunotherapy. Imaging of patients treated with thorium-227 conjugates is challenging due to the low activity administered and to photon emissions with low yields. In addition, the radioactive daughter radium-223 (223Ra) have photon emissions in the same energy range as 227Th. The long half-life of 223Ra (T1/2 = 11.4 d) and the possibility of redistribution motivates efforts to separate 227Th and 223Ra. The aim of this study was to investigate the feasibility of imaging of patients treated with 227Th-labeled-monoclonal antibody (mAb) and to determine acquisition and image processing parameters to enable discrimination between 227Th and 223Ra. Imaging was performed with a GE Discovery 670 NM/CT γ-camera. Radionuclide separation with different energy windows (EW) and collimators was studied in images of vials with either 227Th or 223Ra. Phantom acquisitions with clinically relevant activities were performed to assess image quality and the usefulness of background subtraction and spatial filtering. Two patients treated with 227Th-labeled-mAb were imaged. Imaging of vials showed that 223Ra can be distinguished from 227Th using multiple energy windows. Medium- and high-energy collimators showed similar performance of sensitivity and spatial resolution, whereas the low-energy collimator had higher sensitivity but poor resolution due to collimator penetration. Visually, the image quality was improved with background subtraction and spatial filtering. The patient images exhibited the expected image quality and a possibility to separate 227Th and 223Ra. γ-Camera imaging of patients treated with 227Th-mAb is feasible and 223Ra can be distinguished from 227Th. Image quality is substantially improved using background subtraction and a spatial smoothing filter. Acquisition settings recommended for planar images are: high-energy general purpose or medium-energy general purpose collimator, 40 min acquisition time and energy windows: (1) 70-100 keV (227Th and 223Ra); (2) 215-260 keV (227Th); (3) 260-290 keV (223Ra); (4) 350-420 keV (223Ra).

Qualitative assessments of myocardial ischemia by cardiac MRI and coronary stenosis by invasive coronary angiography in relation to quantitative perfusion by positron emission tomography in patients with known or suspected stable coronary artery disease.

BACKGROUND: To relate findings of qualitative evaluation of first-pass perfusion-CMR and anatomical evaluation on coronary angiography (CA) to the reference standard of quantitative perfusion, cardiac PET, in patients with suspected or known stable coronary artery disease (CAD). METHODS AND RESULTS: Forty-one patients referred for CA due to suspected stable CAD, prospectively performed adenosine stress/rest first-pass perfusion-CMR as well as 13N-NH3 PET on the same day, 4 ± 3 weeks before CA. Angiographers were blinded to PET and CMR results. Regional myocardial flow reserve (MFR) < 2.0 on PET was considered pathological. Vessel territories with stress-induced ischemia by CMR or vessels with stenosis needing revascularization had a significantly lower MFR compared to those with no regional stress-induced ischemia or vessels not needing revascularization (P < 0.001). In 4 of 123 vessel territories with stress-induced ischemia by CMR, PET showed a normal MFR. In addition, 12 of 123 vessels that underwent intervention showed normal MFR assessed by PET. CONCLUSION: The limited performance of qualitative assessment of presence of stable CAD with CMR and CA, when related to quantitative 13N-NH3 cardiac PET, shows the need for fully quantitative assessment of myocardial perfusion and the use of invasive flow reserve measurements for CA, to confirm the need of elective revascularization.

Comparison of conventional and Si-photomultiplier-based PET systems for image quality and diagnostic performance.

BACKGROUND: A new generation of positron emission tomography with computed tomography (PET-CT) was recently introduced using silicon (Si) photomultiplier (PM)-based technology. Our aim was to compare the image quality and diagnostic performance of a SiPM-based PET-CT (Discovery MI; GE Healthcare, Milwaukee, WI, USA) with a time-of-flight PET-CT scanner with a conventional PM detector (Gemini TF; Philips Healthcare, Cleveland, OH, USA), including reconstruction algorithms per vendor's recommendations. METHODS: Imaging of the National Electrical Manufacturers Association IEC body phantom and 16 patients was carried out using 1.5 min/bed for the Discovery MI PET-CT and 2 min/bed for the Gemini TF PET-CT. Images were analysed for recovery coefficients for the phantom, signal-to-noise ratio in the liver, standardized uptake values (SUV) in lesions, number of lesions and metabolic TNM classifications in patients. RESULTS: In phantom, the correct (> 90%) activity level was measured for spheres ≥17 mm for Discovery MI, whereas the Gemini TF reached a correct measured activity level for the 37-mm sphere. In patient studies, metabolic TNM classification was worse using images obtained from the Discovery MI compared those obtained from the Gemini TF in 4 of 15 patients. A trend toward more malignant, inflammatory and unclear lesions was found using images acquired with the Discovery MI compared with the Gemini TF, but this was not statistically significant. Lesion-to-blood-pool SUV ratios were significantly higher in images from the Discovery MI compared with the Gemini TF for lesions smaller than 1 cm (p < 0.001), but this was not the case for larger lesions (p = 0.053). The signal-to-noise ratio in the liver was similar between platforms (p = 0.52). Also, shorter acquisition times were possible using the Discovery MI, with preserved signal-to-noise ratio in the liver. CONCLUSIONS: Image quality was better with Discovery MI compared to conventional Gemini TF. Although no gold standard was available, the results indicate that the new PET-CT generation will provide potentially better diagnostic performance.

A Prospective Observational Study to Evaluate the Effects of Long-Acting Somatostatin Analogs on 68Ga-DOTATATE Uptake in Patients with Neuroendocrine Tumors.

Patients with neuroendocrine tumors (NETs) are often treated with somatostatin analogs (SSAs) for control of symptoms and tumor growth. Such therapy could theoretically lead to misinterpretation of somatostatin receptor imaging with 68Ga-DOTATATE PET/CT by interfering with tracer-receptor binding. Guidelines recommend an interval of 3-4 wk between the last dose and imaging. The aim of this study was to evaluate if long-acting (LA) SSA treatment changes the uptake of 68Ga-DOTATATE in patients with NETs. Methods: From 2013 to 2016, 296 patients with, or under evaluation for, NETs were included in this prospective observational study. The effect of LA SSA on tracer uptake was evaluated in 2 main patient populations: those undergoing 68Ga-DOTATATE PET/CT before starting LA SSA treatment and at least once afterward, and those receiving ongoing LA SSA therapy, in whom the effect of the interval between the last dose of LA SSA and the PET/CT exam was analyzed. A third, explorative, analysis was performed to evaluate if clinical disease progression, regression, or stable tumor status changed the uptake of 68Ga-DOTATATE. In the 3 analyses, measurements of SUVmax in normal liver and tumor lesions were compared. Results: The median SUVmax in normal liver was significantly higher before treatment (8.6; interquartile range, 7.4-10.2) than after treatment initiation (6.0; 4.7-8.0) (P < 0.001). No significant changes in SUVmax were seen in tumor lesions after treatment initiation. No significant differences in SUVmax were found in normal liver or tumor lesions dependent on the interval between last dose of LA SSA and PET/CT. Conclusion: Treatment with LA SSA does not change SUVmax in tumor lesions, whereas SUVmax in normal liver is significantly lower after treatment. The findings have implications for interpretation of 68Ga-DOTATATE PET/CT for response assessment after SSA therapy and for guidelines on discontinuation of treatment before PET/CT.

Differences in attenuation pattern in myocardial SPECT between CZT and conventional gamma cameras.

BACKGROUND: In myocardial perfusion imaging (MPI), single-photon emission tomography (SPECT) soft-tissue attenuation by the abdomen, breasts, and lateral chest wall may create artifacts that mimic true perfusion defects. This may cause misdiagnosis of myocardial perfusion. The aim of the present study was to compare the localization, extent, and depth of attenuation artifacts in MPI SPECT for a multi-pinhole cadmium zinc telluride (CZT) camera vs a conventional gamma camera. METHODS: Phantom and patient measurements were performed using a CZT camera (GE NM 530c) and a conventional gamma camera (GE Ventri). All images were attenuation corrected with externally acquired low-dose computed tomography. The localization, extent, and depth of the attenuation artifact were quantified by comparing attenuation-corrected and non-attenuation-corrected images. RESULTS: Attenuation artifacts were shifted from the inferolateral wall to the lateral wall using the CZT camera compared to a conventional camera in both the patient and the phantom. The extent of the attenuation artifact was significantly larger for the CZT camera compared to the conventional camera (23 ± 5% vs 15 ± 5%, P < .001) for patients and the result was similar for the phantom (28% vs 19%). Furthermore, the depth of the attenuation artifact (percent of maximum counts) was less pronounced for the CZT camera than for the conventional camera, both for phantom measurements (73% vs 67%) and patients (72 ± 3% vs 68 ± 4%, P < .001). CONCLUSIONS: Attenuation artifacts are found in different locations to different extents and depths when using a CZT camera vs a conventional gamma camera for MPI SPECT. This should be taken into consideration when evaluating MPI SPECT studies to avoid misinterpretation of myocardial perfusion distribution.

Excretion and whole-body retention of radium-223 dichloride administered for the treatment of bone metastases from castration resistant prostate cancer.

OBJECTIVE: The aim of the study was to determine the fraction of administered activity that was excreted and retained by a small cohort of patients who each received treatment with radium-223 dichloride (Ra). Ra is an α-emitting radionuclide that has been approved for use in the treatment of bone metastases that are secondary to castration resistant prostate cancer. PATIENTS AND METHODS: Six patients received two weight-based administrations of Ra 6 weeks apart. Activity excreted in the urine and faeces during the first 48 h following each treatment was assessed by direct counting of the excreta. During the same period the whole-body retention of Ra was also determined using a single probe counting system. The results of the excreta counting and the whole-body counting were compared to determine whether whole-body counting was a suitable surrogate for assessing excretion. Further whole-body retention counts were made at around 3, 4, 7 and 42 days following treatment. RESULTS: Patterns of excretion and retention of Ra varied significantly between patients, but were similar for each patient's pair of treatments. The cumulative maximum activity excreted in the initial 8-h period following the Ra administration was 2.6% that increased to 39% at 48 h. The median excreted activity at ~1 and 6 weeks after treatment was 70 and 86%, respectively. Skeletal retention of Ra at 6 weeks ranged from 11 to 60% of the administered activity.

Fully quantitative cardiovascular magnetic resonance myocardial perfusion ready for clinical use: a comparison between cardiovascular magnetic resonance imaging and positron emission tomography.

BACKGROUND: Recent studies have shown that quantification of myocardial perfusion (MP) at stress and myocardial perfusion reserve (MPR) offer additional diagnostic and prognostic information compared to qualitative and semi-quantitative assessment of myocardial perfusion distribution in patients with coronary artery disease (CAD). Technical advancements have enabled fully automatic quantification of MP using cardiovascular magnetic resonance (CMR) to be performed in-line in a clinical workflow. The aim of this study was to validate the use of the automated CMR perfusion mapping technique for quantification of MP using 13N-NH3 cardiac positron emission tomography (PET) as the reference method. METHODS: Twenty-one patients with stable CAD were included in the study. All patients underwent adenosine stress and rest perfusion imaging with 13N-NH3 PET and a dual sequence, single contrast bolus CMR on the same day. Global and regional MP were quantified both at stress and rest using PET and CMR. RESULTS: There was good agreement between global MP quantified by PET and CMR both at stress (-0.1 ± 0.5 ml/min/g) and at rest (0 ± 0.2 ml/min/g) with a strong correlation (r = 0.92, p < 0.001; y = 0.94× + 0.14). Furthermore, there was strong correlation between CMR and PET with regards to regional MP (r = 0.83, p < 0.001; y = 0.87× + 0.26) with a good agreement (-0.1 ± 0.6 ml/min/g). There was also a significant correlation between CMR and PET with regard to global and regional MPR (r = 0.69, p = 0.001 and r = 0.57, p < 0.001, respectively). CONCLUSIONS: There is good agreement between MP quantified by 13N-NH3 PET and dual sequence, single contrast bolus CMR in patients with stable CAD. Thus, CMR is viable in clinical practice for quantification of MP.

The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer.

PURPOSE: The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of 223Ra-dichloride, to assess the relationship between those doses and corresponding 18F-fluoride uptake and to assess the potential of quantitative 18F-fluoride imaging to predict response to treatment. METHODS: Five patients received two intravenous injections of 223Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of 223Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial 223Ra scans. PET/CT imaging using 18F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline. RESULTS: Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5-11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in 18F-fluoride uptake was demonstrated (r2 = 0.52). A log-linear relationship was demonstrated (r2 = 0.77) between baseline measurements of 18F-fluoride uptake prior to 223Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both 223Ra and 18F-fluoride uptake in lesions (r = 0.75) as well as between 223Ra absorbed dose and 18F-fluoride uptake (r = 0.96). CONCLUSIONS: There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between 223Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of 18F-fluoride in bone metastases is significantly correlated with corresponding uptake of 223Ra, the associated 223Ra absorbed dose and subsequent lesion response to treatment.

The radiation dose to overweighted patients undergoing myocardial perfusion SPECT can be significantly reduced: validation of a linear weight-adjusted activity administration protocol.

BACKGROUND: Large body size can cause a higher proportion of emitted photons being attenuated within the patient. Therefore, clinical myocardial perfusion SPECT (MPS) protocols often include unproportionally higher radioisotope activity to obese patients. The aim was to evaluate if a linear weight-adjusted low-dose protocol can be applied to obese patients and thereby decrease radiation exposure. METHODS AND RESULT: Two hundred patients (>110 kg, BMI 18-41, [n = 69], ≤ 110 kg, BMI 31-58, [n = 131]) underwent 99mTc-tetrofosmin stress examination on a Cadmium Zinc Telluride or a conventional gamma camera using new generations of reconstruction algorithm (Resolution Recovery). Patients <110 kg were administered 2.5 MBq/kg, patients between 110 and 120 kg received 430 MBq and patients >120 kg received 570 MBq according to clinical routine. Patients >110 kg had 130% total number of counts in the images compared to patients <110 kg. Recalculating the counts to correspond to an administered activity of 2.5 MBq/kg resulted in similar number of counts across the groups. Image analyses in a subgroup with images corresponding to high activity and 2.5 MBq/kg showed no difference in image quality or ischemia quantification. CONCLUSION: Linear low-dose weight-adjusted protocol of 2.5 MBq/kg in MPS can be applied over a large weight span without loss of counts or image quality, resulting in a significant reduction in radiation exposure to obese patients.