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The aim of this study was to evaluate strategies to reduce contrast media volumes for coronary computed tomography (CT) angiography on a clinical first-generation dual-source photon-counting detector (PCD)-CT system using a dynamic circulation phantom.Coronary CT angiograph is an established method for the assessment of coronary artery disease that relies on the administration of iodinated contrast media. Reduction of contrast media volumes while maintaining diagnostic image quality is desirable. In this study, a dynamic phantom containing a 3-dimensional-printed model of the thoracic aorta and coronary arteries was evaluated using a clinical contrast injection protocol with stepwise reduced contrast agent concentrations (100%, 75%, 50%, 40%, 30%, and 20% contrast media content of the same 50 mL bolus, resulting in iodine delivery rates of 1.5, 1.1, 0.7, 0.6, 0.4 and 0.3 gl/s) on a first-generation, dual-source PCD-CT. Polychromatic images (T3D) and virtual monoenergetic images were reconstructed in the range of 40 to 70 keV in 5-keV steps. Attenuation and noise were measured in the coronary arteries and background material and the contrast-to-noise ratio (CNR) were calculated. Attenuation of 350 HU and a CNR of the reference protocol at 70 keV were regarded as sufficient for simulation of diagnostic purposes. Vessel sharpness and noise power spectra were analyzed for the aforementioned reconstructions.The standard clinical contrast protocol (bolus with 100% contrast) yielded diagnostic coronary artery attenuation for all tested reconstructions (398 HU). A 50% reduction in contrast media concentration demonstrated sufficient attenuation of the coronary arteries at 40 to 55 keV (366 HU). Virtual monoenergetic image reconstructions of 40 to 45 and 40 keV allowed satisfactory attenuation of the coronary arteries for contrast concentrations of 40% and 30% of the original protocol. A reduction of contrast agent concentration to 20% of the initial concentration provided insufficient attenuation in the target vessels for all reconstructions. The highest CNR was found for virtual monoenergetic reconstructions at 40 keV for all contrast media injection protocols, yielding a sufficient CNR at a 50% reduction of contrast agent concentration.Using virtual monoenergetic image reconstructions at 40 keV on a dual-source PCD-CT system, contrast media concentration could be reduced by 50% to obtain diagnostic attenuation and objective image quality for coronary CT angiography in a dynamic vessel phantom. These initial feasibility study results have to be validated in clinical studies.

The burden of coronavirus disease 2019 (COVID-19) airspace opacities is time consuming and challenging to quantify on computed tomography. The purpose of this study was to evaluate the ability of a deep convolutional neural network (dCNN) to predict inpatient outcomes associated with COVID-19 pneumonia.A previously trained dCNN was tested on an external validation cohort of 241 patients who presented to the emergency department and received a chest computed tomography scan, 93 with COVID-19 and 168 without. Airspace opacity scoring systems were defined by the extent of airspace opacity in each lobe, totaled across the entire lungs. Expert and dCNN scores were concurrently evaluated for interobserver agreement, while both dCNN identified airspace opacity scoring and raw opacity values were used in the prediction of COVID-19 diagnosis and inpatient outcomes.Interobserver agreement for airspace opacity scoring was 0.892 (95% CI 0.834-0.930). Probability of each outcome behaved as a logistic function of the opacity scoring (25% intensive care unit admission at score of 13/25, 25% intubation at 17/25, and 25% mortality at 20/25). Length of hospitalization, intensive care unit stay, and intubation were associated with larger airspace opacity score (p = 0.032, 0.039, 0.036, respectively).The tested dCNN was highly predictive of inpatient outcomes, performs at a near expert level, and provides added value for clinicians in terms of prognostication and disease severity.

The aim of this study was to evaluate coronary computed tomography angiography (CCTA)-based in vitro and in vivo coronary artery calcium scoring (CACS) using a novel virtual noniodine reconstruction (PureCalcium) on a clinical first-generation photon-counting detector-computed tomography system compared with virtual noncontrast (VNC) reconstructions and true noncontrast (TNC) acquisitions.Although CACS and CCTA are well-established techniques for the assessment of coronary artery disease, they are complementary acquisitions, translating into increased scan time and patient radiation dose. Hence, accurate CACS derived from a single CCTA acquisition would be highly desirable. In this study, CACS based on PureCalcium, VNC, and TNC, reconstructions was evaluated in a CACS phantom and in 67 patients (70 [59/80] years, 58.2% male) undergoing CCTA on a first-generation photon counting detector-computed tomography system. Coronary artery calcium scores were quantified for the 3 reconstructions and compared using Wilcoxon test. Agreement was evaluated by Pearson and Spearman correlation and Bland-Altman analysis. Classification of coronary artery calcium score categories (0, 1-10, 11-100, 101-400, and400) was compared using Cohen κ .Phantom studies demonstrated strong agreement between CACS PureCalcium and CACS TNC (60.7 ± 90.6 vs 67.3 ± 88.3, P = 0.01, r = 0.98, intraclass correlation [ICC] = 0.98; mean bias, 6.6; limits of agreement [LoA], -39.8/26.6), whereas CACS VNC showed a significant underestimation (42.4 ± 75.3 vs 67.3 ± 88.3, P0.001, r = 0.94, ICC = 0.89; mean bias, 24.9; LoA, -87.1/37.2). In vivo comparison confirmed a high correlation but revealed an underestimation of CACS PureCalcium (169.3 [0.7/969.4] vs 232.2 [26.5/1112.2], P0.001, r = 0.97, ICC = 0.98; mean bias, -113.5; LoA, -470.2/243.2). In comparison, CACS VNC showed a similarly high correlation, but a substantially larger underestimation (24.3 [0/272.3] vs 232.2 [26.5/1112.2], P0.001, r = 0.97, ICC = 0.54; mean bias, -551.6; LoA, -2037.5/934.4). CACS PureCalcium showed superior agreement of CACS classification ( κ = 0.88) than CACS VNC ( κ = 0.60).The accuracy of CACS quantification and classification based on PureCalcium reconstructions of CCTA outperforms CACS derived from VNC reconstructions.

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks.

Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy in patients with cancer. HER2 expression in a complex environment, such as in a heterogeneous tumor, makes the precise assessment of the HER2 status difficult using current methods. In this study, we developed a novel 99mTc-labeled anti-HER2 single-domain antibody (99mTc-NM-02) as a molecular imaging tracer for the noninvasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in 10 patients with breast cancer. Our data showed that no drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid; however, only background tracer levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10-3 mSv/MBq, and tracer uptake was visually observed in the primary tumors and metastases. A maximal standard uptake value of 1.5 was determined as a reasonable cutoff for identifying HER2 positivity using SPECT/CT imaging. Our 99mTc-NM-02 tracer is safe for use in breast cancer imaging, with reasonable radiation doses, favorable biodistribution, and imaging characteristics. 99mTc-NM-02 SPECT imaging may be an accurate and noninvasive method to detect the HER2 status in patients with breast cancer.

Introduction: The roles and responsibilities of medical physicists (MPs) are growing together with the evolving science and technology. The complexity of today's clinical trials requires the skills and knowledge of MPs for their safe and efficient implementation. However, it is unclear to what extent the skillsets offered by MPs are being exploited in clinical trials across Europe. Methods: The EFOMP Working Group on the role of Medical Physics Experts in Clinical Trials has designed a survey that targeted all 36 current National Member Organisations, receiving a response from 31 countries. The survey included both quantitative and qualitative queries regarding the involvement of MPs in trial design, setup, and coordination, either as trial team members or principal investigators. Results: The extent of MPs involvement in clinical trials greatly varies across European countries. The results showed disparities between the roles played by MPs in trial design, conduct or data processing. Similarly, differences among the 31 European countries that responded to the survey were found regarding the existence of national bodies responsible for trials or the available training offered to MPs. The role of principal investigator or co-investigator was reported by 12 countries (39%), a sign of efficient collaboration with medical doctors in designing and implementing clinical studies. Conclusion: Organisation of specific training courses and guideline development for clinical trial design and conduct would encourage the involvement of a larger number of MPs in all stages of trials across Europe, leading to a better standardisation of clinical practice. Refereed/Peer-reviewed

Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism.Patients with confirmed primary aldosteronism underwent both AVS and 11C-Metomidate PET-CT (post-dexamethasone). All results were reviewed at a multidisciplinary meeting to decide on final subtype diagnosis. Primary outcome was accuracy of PET versus AVS to diagnosis of unilateral primary aldosteronism based on post-surgical biochemical cure. Secondary outcome was accuracy of both tests to final subtype diagnosis.All 25 patients recruited underwent PET and successful AVS (100%). Final diagnosis was unilateral in 22 patients, bilateral in two and indeterminate in one due to discordant lateralization. Twenty patients with unilateral primary aldosteronism underwent surgery, with 100% complete biochemical success, and 75% complete/partial clinical success. For the primary outcome, sensitivity of PET was 80% [95% confidence interval (95% CI): 56.3-94.3] and AVS was 75% (95% CI: 50.9-91.3). For the secondary outcome, sensitivity and specificity of PET was 81.9% (95% CI: 59.7-94.8) and 100% (95% CI: 15.8-100), and AVS was 68.2% (95% CI: 45.1-86.1) and 100% (95% CI: 15.8-100), respectively. Twelve out of 20 (60%) patients had both PET and AVS lateralization, four (20%) PET-only, three (15%) AVS-only, while one patient did not lateralize on PET or AVS. Post-surgery outcomes did not differ between patients identified by either test.In our pilot study, 11C-Metomidate PET-CT performed comparably to AVS, and this should be validated in larger studies. PET identified patients with unilateral primary aldosteronism missed on AVS, and these tests could be used together to identify more patients with unilateral primary aldosteronism.http://links.lww.com/HJH/B918.

Metaiodobenzylguanidine (MIBG) imaging has been the standard for neuroblastoma staging for many decades. Novel agents such as 18F-DOPA and 68Ga-DOTATATE are being used nowadays in academic centers. During the coronavirus disease 2019 (COVID-19) pandemic, procurement of 123I-MIBG has proved particularly challenging, necessitating the use of 68Ga-DOTATATE PET. 68Ga-DOTATATE is Food and Drug Administration–approved for imaging of somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. Methods:68Ga-DOTATATE PET/CT imaging was performed for staging of 3 pediatric patients with neuroblastoma at our institution. A review of the literature was also completed. Results:68Ga-DOTATATE PET/CT scans were successfully performed on all patients. All patients showed 68Ga-DOTATATE–avid disease. PET scans showed an excellent spatial resolution and demonstrated high accuracy in concordance with current European Association of Nuclear Medicine guidelines. Conclusion: We have presented 68Ga-DOTATATE PET/CT imaging for staging of neuroblastoma and believe it can reliably be used as an alternative to 123I-MIBG. It has technical, clinical, and practical advantages making it an attractive option. Further multicenter studies are required before it can be recommended for standard clinical use.

PurposeThe conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.MethodsIn this test–retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).ResultsConcentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constantk3(related to GS activity) fromK1(related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammoniaK1correlated reliably (r2 = 0.72–0.92) with [15O]water CBF.ConclusionThe [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

To assess the impact of scan modes and reconstruction kernels using a novel dual-source photon-counting detector CT (PCD-CT) on lumen visibility and sharpness of different stent sizes.A phantom containing six balloon-expandable stents (2.5 to 9 mm diameter) in silicone tubing was scanned on a PCD-CT with standard (0.6 mm and 0.4 mm thicknesses) and ultra-high-resolution (0.2 mm thickness) modes. With the use of increasing contrast medium concentrations, densities of 0, 200, 400, and 600 HU were achieved. Standard-resolution scans were reconstructed using increasing sharpness kernels, using both polyenergetic quantitative soft tissue "conventional" ((Qr40In-stent lumen visibility was highest for Qr72UHR acquisition mode and sharp reconstruction kernels on a novel PCD-CT system significantly improve in-stent lumen visibility and sharpness-especially for smaller stent sizes.• In-stent lumen visibility and sharpness of stents significantly improve using sharp reconstruction kernels (Bv60) and ultra-high-resolution mode in photon-counting detector computed tomography. • The observed improvement of stent-lumen visibility was highest in smaller stent sizes.

Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy in patients with cancer. HER2 expression in a complex environment, such as in a heterogeneous tumor, makes the precise assessment of the HER2 status difficult using current methods. In this study, we developed a novel

Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies demonstrates improvements in treatment of advanced non–small cell lung cancer. Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single-domain antibody, NM-01, against PD-L1, radiolabeled site-specifically with 99mTc for SPECT imaging, we aimed to assess the safety, radiation dosimetry, and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results.Methods: Sixteen patients (mean age, 61.7 y; 11 men) with non–small cell lung cancer were recruited. Primary tumor PD-L1 expression was measured by immunohistochemistry. NM-01 was radiolabeled with [99mTc(OH2)3(CO)3]+ complex binding to its C-terminal hexahistidine tag. Administered activity was 3.8–10.4 MBq/kg, corresponding to 100 μg or 400 μg of NM-01. Whole-body planar and thoracic SPECT/CT scans were obtained at 1 and 2 h after injection in all patients, and 5 patients underwent additional imaging at 10 min, 3 h, and 24 h for radiation dosimetry calculations. All patients were monitored for adverse events.Results: No drug-related adverse events occurred in this study. The mean effective dose was 8.84 × 10−3 ± 9.33 × 10−4 mSv/MBq (3.59 ± 0.74 mSv per patient). Tracer uptake was observed in the kidneys, spleen, liver, and bone marrow. SPECT primary tumor–to–blood-pool ratios (T:BP) varied from 1.24 to 2.3 (mean, 1.79) at 1 h and 1.24 to 3.53 (mean, 2.22) at 2 h (P = 0.005). Two-hour primary T:BP ratios correlated with PD-L1 immunohistochemistry results (r = 0.68, P = 0.014). Two-hour T:BP was lower in tumors with ≤1% PD-L1 expression (1.89 vs. 2.49, P = 0.048). Nodal and bone metastases showed tracer uptake. Heterogeneity (>20%) between primary tumor and nodal T:BP was present in 4 of 13 patients.Conclusion: This first-in-human study demonstrates that 99mTc-labeled anti–PD-L1-single-domain antibody SPECT/CT imaging is safe and associated with acceptable dosimetry. Tumor uptake is readily visible against background tissues, particularly at 2 h when the T:BP ratio correlates with PD-L1 immunohistochemistry results.

Background: Accurate determination of human epidermal growth factor receptor 2 (HER2) expression is essential for HER2-targeted therapy. HER2 expression in a complex environment, such as in a heterogenous tumor, makes precise assessment difficult using current methods. Therefore, we developed a novel 99mTc-labeled anti-HER2-single domain antibody (99mTc-NM-02) as a molecular imaging tracer for non-invasive detection of HER2 expression and investigated its safety, radiation dosimetry, biodistribution, and tumor-targeting potential in breast cancer patients.Methods: A lead compound (NM-02) was screened from a library of hexahistidine-tagged anti-HER2-single domain antibodies and labeled with 99mTc for the preparation of 99mTc-NM-02 tracer. Ten women with breast cancer were administered 99mTc-NM-02 at a mean dose of 458 ± 37 MBq (406−510 MBq), corresponding to 100 μg of NM-02. Whole-body and local SPECT/CT images were acquired at 1 and 2 h post-administration to investigate the tumor-targeting potential in primary and metastatic lesions. Additional images were acquired at 10 min, 3 h, and 24 h in three patients to calculate radiation dosimetry. Physical evaluation and blood analysis were performed for safety assessment.Results: No drug-related adverse reactions occurred. The tracer mainly accumulated in the kidneys and liver with mild uptake in the spleen, intestines, and thyroid, but only background levels were observed in other organs where primary tumors and metastases typically occurred. The mean effective dose was 6.56 × 10−3 mSv/MBq, and tracer uptake was visually observed in primary tumors and metastases. Owing to the fast clearance of the tracer, we were able to sufficiently discern uptake over normal background in both primary lesions and metastases within 2 h after injection. A maximal standard uptake value of 1.5 could be a reasonable cutoff for determining HER2 positivity using SPECT/CT imaging.Conclusions: Our 99mTc-NM-02 tracer can be safely used for imaging in breast cancer patients with reasonable radiation doses, favorable biodistribution and imaging characteristics. 99mTc-NM-02 SPECT imaging may provide an accurate and non-invasive method to detect HER2 status in breast cancer patients.Trial registration: ClinicalTrials.gov, NCT04040686. Registered 30 July 2019. https://clinicaltrials.gov/ct2/show/NCT04040686.

Background: MIBG imaging has been the standard for neuroblastoma staging following its discovery 4 decades ago. Novel agents such as 18F-FDOPA and 68Ga-DOTATATE are being widely used nowadays in academic centers. In the midst of the COVID-19 pandemic, procurement of MIBG has proved particularly challenging, necessitating the use of 68Ga DOTATATE positron emission tomography. Methods: 68Ga-DOTATATE PET/CT imaging was carried out for completion of staging investigation for three pediatric patients who were diagnosed with Neuroblastoma at our institution, as 123Iodine MIBG became unavailable during the pandemic. Results: 68Ga-DOTATATE PET/CT scans were carried out in all three pediatric patients without any complications. All patients showed 68Gallium DOTATATE avid disease. PET/CT scans showed better spatial resolution, increased lesion contrast and demonstrated high accuracy in staging neuroblastoma patients in concordance with current EANM guidelines. Conclusion: 68Ga-DOTATATE PET/CT imaging can be reliably used as an alternative to MIBG for staging and evaluation of patients with neuroblastoma. Impact may be best in high risk disease.

Purpose The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.Methods In this test-retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).Results Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k3 (related to GS activity) from K1 (related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N]ammonia to blood (k2). Model selection favoured a reversible one tissue compartmental model, and [13N]ammonia K1 correlated reliably (r2 = 0.72–0.92) with [15O]water CBF.Conclusion The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

Purpose The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans. Methods In this test–retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF). Results Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k3 (related to GS activity) from K1 (related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammonia K1 correlated reliably (r2 = 0.72–0.92) with [15O]water CBF. Conclusion The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

Purpose The intranasal (IN) administration of radiopharmaceuticals is of interest in being a viable route for the delivery of radiopharmaceuticals that do not ordinarily cross the blood-brain barrier (BBB). However, to be viable in a patient population, good image quality as well as safety of the administration should be demonstrated. This work provides radiation dosimetry calculations and simulations related to the radiation safety of performing such experiments in a human cohort. Methods We performed Monte Carlo (MC) simulations to estimate radiation dose to the skin inside a cylindrical model of the nasal cavity assuming a homogenous distribution layer of 11 C and 18 F and calculated a geometry conversion factor (FP-C ) which can be used to convert from a planar geometry to a cylindrical geometry using more widely available software tools. We compared radiation doses from our simulated cylindrical geometry with the planar dose estimates employing our geometry conversion factor from VARSKIN 6.1 software and also from an analytical equation. Furthermore, in order to estimate radiation dosimetry to surrounding organs of interest, we performed a voxelized MC simulation of a fixed radioactivity inside the nasal cavity and calculated S-values to organs such as the eyes, thyroid, and brain. Results MC simulations of contamination scenarios using planar absorbed doses of 15.50 and 8.60 mGy/MBq for 18 F and 11 C, respectively, and 35.70 and 19.80 mGy/MBq per hour for cylindrical geometries, leading to determination of an FP-C of 2.3. Planar absorbed doses (also in units of mGy/MBq) determined by the analytical equation were 16.96 and 8.68 (18 F and 11 C) and using VARSKIN were 16.60 and 9.26 (18 F and 11 C), respectively. Application of FP-C to these results demonstrates values with a maximum difference of 9.41% from the cylindrical geometry MC calculation, demonstrating that when accounting for geometry, more simplistic techniques can be utilized to estimate IN dosimetry. Voxelized MC simulations of radiation dosimetry from a fixed source of 1 MBq of activity confined to the nasal cavity resulted in S-values to the thyroid, eyes, and brain of 1.72 x 10-6 , 1.93 x 10-5 , and 3.51 x 10-6 mGy/MBq·s, respectively, for 18 F and 1.80 × 10-6 , 1.95 × 10-5 , and 3.54 × 10-6 mGy/MBq·s for 11 C. Conclusion Dosimetry concerns about IN administrations of PET radiotracers should be considered before clinical use. Values presented in the simulations such as the S-values can be further used for assessment of absorbed doses in cases of IN administration, and can be used to develop and adapt specific study protocols. All three presented methods provided similar results when considering the use of a geometry conversion factor for planar to cylindrical geometry, demonstrating that standard tools rather than dedicate MC simulations may be used to perform dose calculations in nasal administrations.

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.

Background Positron emission tomography (PET) is the non-invasive reference standard for myocardial blood flow (MBF) quantification. Hybrid PET-MR allows simultaneous PET and cardiac magnetic resonance (CMR) acquisition under identical experimental and physiological conditions. This study aimed to determine feasibility of simultaneous 13N-Ammonia PET and dynamic contrast-enhanced CMR MBF quantification in phantoms and healthy volunteers. Methods Images were acquired using a 3T hybrid PET-MR scanner. Phantom study: MBF was simulated at different physiological perfusion rates and a protocol for simultaneous PET-MR perfusion imaging was developed. Volunteer study: five healthy volunteers underwent adenosine stress. 13N-Ammonia and gadolinium were administered simultaneously. PET list mode data was reconstructed using ordered subset expectation maximisation. CMR MBF was quantified using Fermi function-constrained deconvolution of arterial input function and myocardial signal. PET MBF was obtained using a one-tissue compartment model and image-derived input function. Results Phantom study: PET and CMR MBF measurements demonstrated high repeatability with intraclass coefficients 0.98 and 0.99, respectively. There was high correlation between PET and CMR MBF (r = 0.98, p

Introduction The development of clinically useful tracers for PET imaging is enormously challenging and expensive. The intranasal (IN) route of administration is purported to be a viable route for delivering drugs to the brain but has, as yet, not been investigated for the delivery of PET tracers. If the intranasal (IN) pathway presents a viable option, it extends the PET imaging field by increasing the number of tracers available for human use. Here we report the results of a rodent study testing the feasibility of the IN route to administer radiotracers for brain PET imaging. Methods We used two different, well characterised, brain penetrant radiotracers, [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fallypride, and aimed to evaluate the pharmacokinetics after administration of the tracers via the intranasal route, and contrast this to intravenous administration. Image acquisition was carried out after tracer administration and arterial blood samples were collected at different time intervals, centrifuged to extract plasma and gamma counted. We hypothesised that [brain region]:[plasma] ratios would be higher via the intranasal route as there are two inputs, one directly from the nose to the brain, and another from the peripheral circulation. To assess the feasibility of using this approach clinically, we used these data to estimate radiation dosimetry in humans. Results Contrary to our hypothesis, in case of both radiotracers, we did not see a higher ratio in the expected brain regions, except in the olfactory bulb, that is closest to the nose. It appears that the radiotracers move into the olfactory bulb region, but then do not progress further into other brain regions. Moreover, as the nasal cavity has a small surface area, the extrapolated dosimetry estimations for intranasal human imaging showed an unacceptably high level (15 mSv/MBq) of cumulative skin radiation exposure. Conclusions Therefore, although an attractive route for brain permeation, we conclude that the intranasal route would present difficulties due to non-specific signal and radiation dosimetry considerations for brain PET imaging.

Objective The current procedure at our centre for partitioning multidose vials of fluorine-18-fluorodeoxyglucose (F-FDG) is based on a manual method. To reduce extremity dose while reducing contamination risk, maintaining product sterility and improving the accuracy of injected activity, we recently purchased a new semiautomated partitioning system (μDDS-A). This work reports on the operating characteristics of the system and its validation for clinical use in terms of dispensing accuracy and extremity dose reduction. Methods A range of operators carried out 300 automated partitioning procedures by following a typical working-day setup. The accuracy of the activity resulting from system partitioning compared with true syringe activity was determined. We also determined the precision of system-determined activity when compared with user-requested activity. The cumulative finger dose for automated and manual partitioning techniques was measured at the fingertip using a digital dosimeter, recording the dose at different stages of the procedure. Results The results of comparisons made between the final syringe activity measured by the system and the measurement of the true syringe activity independently of the system were within ±5% for 96.63% of syringes. Precision of the syringe activity provided by the system with respect to the user-requested activity was within ±10% for 96.96% of measurements. Average finger doses compared with a manual partitioning method showed a reduction of up to 80% when relying only on the system measurement of activity. Conclusion The μDDS-A reproducibly partitions a vial of F-FDG and offers a significant reduction in extremity dose to the operator of up to 80% in comparison with a manual partition technique.

REPLY: We thank Laffon and Marthan for their interest in our study ([1][1]). They discuss the influence of measurement uncertainty on the ability to detect changes in measurements. We refer them to previous work by members of our group ([2][2]) that compared 18F-fluoride Ki measurement derived from

In 3D PET an axial compression is often applied to reduce the data size and the computation times during image reconstruction. This compression scheme can achieve good results in the centre of the FOV. However, there is a loss in the spatial resolution at off-centre positions and this effect is increased in scanners with a larger FOV. This is the case for the Siemens Biograph mMR, which by default uses an axial compression of span 11. An assessment of the improvement in the spatial resolution that would be achieved in a reconstruction without axial compression, is necessary to evaluate if the additional computational burden is justified for routine image reconstruction. In this work, we present an implementation of the ordinary Poisson ordered subsets expectation maximization (OP-OSEM) algorithm without axial compression for the mMR, and evaluate its performance for span 1 and span 11. We show that an improvement of 3 mm FWHM (i.e. an improvement of 40%) can be achieved when span 11 compression is avoided and the source is at a distance greater than 100 mm from the centre of the FOV. In addition, the general image quality properties of the algorithm were evaluated with a NEMA image quality phantom acquisition and contrasted with its reconstruction via the STIR open source reconstruction software.

BACKGROUND Treatment of inoperable hepatocellular carcinoma or secondary metastases by radioembolization using yttrium-90 (90Y) microspheres is a promising method for the treatment of unresectable liver metastases. A pretreatment scintigraphy planar scan using 99mTc-labelled macroaggregated albumin (99mTc-MAA) injected directly into the hepatic artery is carried out to assess the degree of portal shunting of blood between the liver and the lungs. The quantitative results of this scan are used to modulate the activity of therapeutic 90Y microspheres injected into the patient to limit the radiation dose received by the lungs. The presence of scattered events in the MAA lung shunt scan leads to an overestimation of the true shunting ratio, which in turn leads to the administered therapeutic activity being lowered unnecessarily to comply with the protocols of radiation protection. Overall, this may impact the efficacy of treatment. MATERIALS AND METHODS This study analyses the impact of a window-based analytical scatter-correction method on lung shunt analysis using an anthropomorphic torso phantom, and retrospectively analysed three patient case studies. RESULTS Our results of scatter in the phantom show a marked decrease in the lung shunt percentage. Clinical analysis of patient data shows that the lung shunt percentage can be overestimated by up to 50% in clinical cases, and depending on the lung shunt percentage, the efficacy of treatment by therapeutic dose reduction may be compromised. CONCLUSION Our results indicate that scatter correction should be used on 90Y pretreatment 99mTc-MAA scans in order to more accurately assess the lung shunting percentage before therapy.

Lipoma arborescens (LA) in the knee is a benign intra-articular lipomatous proliferation of the synovial membrane, and data on treatment of LA by radionuclide therapy is sparse. We present a rare case of bilateral LA in the knees successfully treated with injection of Y-citrate colloid. We assessed the biodistribution of the radiopharmaceutical through the use of SPECT/CT imaging. Our images show slight redistribution of the radiocolloid in the knee joint, whereas most of the radioactivity remains localized around the LA. MRI scans confirmed the efficacy of this treatment, with a significant reduction in LA volume after 6 months.

Visible and near-infrared light, particularly in the wavelength region of 600–1100 nm, offer a window into human and animal tissues due to reduced scattering and absorption. We review the main biophotonic methods applied to visualisation and assessment of the microcirculation and document the progress made over the past 10 years in particular. Applications, particularly in human skin, are of special topical importance due to an improved knowledge of its role and its value as a surrogate for other organs in drug testing at a time when drug development is under severe pressure.

18F-fluoride PET/CT offers the opportunity for accurate skeletal metastasis staging, compared with conventional imaging methods. 18F-fluoride is a bone-specific tracer whose uptake depends on osteoblastic activity. Because of the resulting increase in bone mineralization and sclerosis, the osteoblastic process can also be detected morphologically in CT images. Although CT is characterized by high resolution, the potential of PET is limited by its lower spatial resolution and the resulting partial-volume effect. In this context, the synergy between PET and CT presents an opportunity to resolve this limitation using a novel multimodal approach called synergistic functional–structural resolution recovery (SFS-RR). Its performance is benchmarked against current resolution recovery technology using the point-spread function (PSF) of the scanner in the reconstruction procedure. Methods: The SFS-RR technique takes advantage of the multiresolution property of the wavelet transform applied to both functional and structural images to create a high-resolution PET image that exploits the structural information of CT. Although the method was originally conceived for PET/MR imaging of brain data, an ad hoc version for whole-body PET/CT is proposed here. Three phantom experiments and 2 datasets of metastatic bone 18F-fluoride PET/CT images from primary prostate and breast cancer were used to test the algorithm performances. The SFS-RR images were compared with the manufacturer’s PSF-based reconstruction using the standardized uptake value (SUV) and the metabolic volume as metrics for quantification. Results: When compared with standard PET images, the phantom experiments showed a bias reduction of 14% in activity and 1.3 cm3 in volume estimates for PSF images and up to 20% and 2.5 cm3 for the SFS-RR images. The SFS-RR images were characterized by a higher recovery coefficient (up to 60%) whereas noise levels remained comparable to those of standard PET. The clinical data showed an increase in the SUV estimates for SFS-RR images up to 34% for peak SUV and 50% for maximum SUV and mean SUV. Images were also characterized by sharper lesion contours and better lesion detectability. Conclusion: The proposed methodology generates PET images with improved quantitative and qualitative properties. Compared with standard methods, SFS-RR provides superior lesion segmentation and quantification, which may result in more accurate tumor characterization.

Multimodality imaging techniques (PET/CT and PET/MR) offer the opportunity of integrating functional and anatomical information to improve clinical diagnostic accuracy.