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Introduction: Although the use of 68Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to 68Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of 68Ga-labelled radiopharmaceuticals. Method: Workers in eight centres wore a ring dosimeter for all tasks involving 68Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during 68Ga procedures was also identified in one centre. Results: The median normalised ring dose for 68Ga procedures was found to be 0.25 mSv GBq−1 (range 0.01–3.34). The normalised 68Ga ring doses recorded in this study are similar to that found in the literature for 18F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual 68Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv). Conclusion: When appropriate shielding and radiation protection practices are employed, the extremity dose due to 68Ga is comparable to that of 18F and is expected to be well below the regulatory limits for the majority of workers.

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed as well as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies. ispartof: NUCLEAR MEDICINE AND BIOLOGY vol:100 pages:61-90 ispartof: location:United States status: published

OBJECTIVES This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing. BACKGROUND Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris. METHODS Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with >= 50% stenosis on CT angiography underwent CT myocardial perfusion imaging. RESULTS By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001). CONCLUSIONS In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484) (C) 2018 by the American College of Cardiology Foundation.

BACKGROUND Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease. HYPOTHESIS/OBJECTIVES To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection. ANIMALS Sixty-eight dogs with thyroid neoplasia. METHODS Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018). RESULTS Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia.

Background: Diagnosing diabetic foot infection is often difficult, despite several available diagnostic methods. Amongst these, several imaging modalities exist to evaluate the diabetic foot in case of a suspected osteomyelitis. Nuclear Medicine, in particular, offers a variety of radiopharmaceuticals and techniques. Nowadays the gold standard radionuclide procedure, when an osteomyelitis is suspected, is represented by the use of radiolabelled leukocytes with either Tc-99m-HMPAO or In-111-oxine.Methods: In this review, we describe the correct acquisition and interpretation of white blood cell scintigraphy and we provide an overview of the existing literature data of the use of this technique in the infected diabetic foot. If images are correctly acquired, displayed and interpreted, this modality reaches very high diagnostic accuracy (>95%) in detecting osteomyelitis and it allows the differential diagnosis with a soft tissue infection or inflammation. Single-photon emission computed tomography/computed tomography (SPECT/CT) in addition to planar images is mandatory to determine the extent and exact location of the infective process in both fore foot and mid-hint foot. With the addition of bone marrow scintigraphy using radiolabelled nanocolloids, radiolabelled white blood cell scintigraphy is also able to differentiate between Charcot neuroarthropathy and osteomyelitis, which is a challenge in the evaluation of diabetic foot. Radiolabelled anti-granulocyte monoclonal antibodies and their fragments can also be used instead of white blood cells although there is a limited experience on their usefulness in diabetic foot infection.

Long-lived europium-154 impurities are formed during the production of medical samarium-153 in a high-flux nuclear reactor. A method to separate these europium impurities from samarium was investigated using the hydrophobic quaternary ammonium ionic liquid Aliquat 336 nitrate. The separation method consists of the selective reduction of Eu3+ by zinc metal in an aqueous feed solution containing a high nitrate salt concentration. Subsequent extraction using undiluted Aliquat 336 nitrate leads to an efficient separation of both lanthanides in a relatively short time frame. Sm3+ was extracted to the neat ionic liquid phase much more efficiently than Eu2+. An initial approach using the addition of dicyclohexano-18-crown-6 to capture Eu2+ in the ionic liquid phase was less efficient. ispartof: RSC ADVANCES vol:8 issue:36 pages:20077-20086 ispartof: location:England status: published

Computational phantoms are commonly used in internal radiation dosimetry to assess the amount and distribution pattern of energy deposited in various parts of the human body from different internal radiation sources. Radiation dose assessments are commonly performed on predetermined reference computational phantoms while the argument for individualized patient-specific radiation dosimetry exists. This study aims to evaluate the influence of body habitus on internal dosimetry and to quantify the uncertainties in dose estimation correlated with the use of fixed reference models. The 5-year-old IT'IS male phantom was modified to match target anthropometric parameters, including body weight, body height and sitting height/stature ratio (SSR), determined from reference databases, thus enabling the creation of 125 5-year-old habitus-dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body morphometries. We evaluated the absorbed fractions and the mean absorbed dose to the target region per unit cumulative activity in the source region (S-values) of F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code and calculated the absorbed dose and effective dose of five 18F-labelled radiotracers for children of various habitus. For most organs, the S-value of F-18 presents stronger statistical correlations with body weight, standing height and sitting height than BMI and SSR. The self-absorbed fraction and self-absorbed S-values of F-18 and the absorbed dose and effective dose of 18F-labelled radiotracers present with the strongest statistical correlations with body weight. For 18F-Amino acids, 18F-Brain receptor substances, 18F-FDG, 18F-L-DOPA and 18F-FBPA, the mean absolute effective dose differences between phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%, 13.3% and 11.4%, respectively. Total body weight, standing height and sitting height have considerable effects on human internal dosimetry. Radiation dose calculations for individual subjects using the most closely matched habitus-dependent computational phantom should be considered as an alternative to improve the accuracy of the estimates.

Objectives An electronic training programme (ETP) was developed for interpretation of images during routine clinical use of the PET amyloid imaging agent [18F] flutemetamol injection (VIZAMYL). This study was carried out to validate the ETP.Materials and methods Five nuclear medicine technologists (NMTs) and five readers previously inexperienced in amyloid image interpretation were required to self-train using the ETP and pass a test to participate. A total of 305 [18F] flutemetamol PET images were then tested as the validation set, following preassessment and reorientation (where required) by one of five NMTs. Next, a new set of readers blinded to clinical information independently assessed all 305 images. Images had been acquired in previous studies from patients representing the full spectrum of cognitive capacity. When available, a standard of truth determined by histopathology or clinical history was used to derive sensitivity and specificity for image interpretation from this validation set. Randomly selected images (n= 29) were read in duplicate to measure intrareader reproducibility. Images were read first without, and subsequently with anatomic images, if available.Results All NMTs and all readers scored 100% on the qualifying test. The interpretation of 135 cases without anatomic image support resulted in sensitivity ranging from 84% to 94% (majority 94%, median 92%) and specificity ranging from 77% to 96% (majority 92%, median 81%). Inter-reader agreement was very high, with most kappa scores more than 0.8. Intrareader reproducibility ranged from 93 to 100%.Conclusion The self-guided ETP effectively trained new amyloid PET image readers to accurately and reproducibly interpret [F-18] flutemetamol PET images. Nucl Med Commun 38:234-241 Copyright (C) 2017 The Author(s). Published by Wolters Kluwer Health, Inc.

OBJECTIVES This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing. BACKGROUND Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris. METHODS Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with >= 50% stenosis on CT angiography underwent CT myocardial perfusion imaging. RESULTS By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001). CONCLUSIONS In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484) (C) 2018 by the American College of Cardiology Foundation.

Background: Diagnosing diabetic foot infection is often difficult, despite several available diagnostic methods. Amongst these, several imaging modalities exist to evaluate the diabetic foot in case of a suspected osteomyelitis. Nuclear Medicine, in particular, offers a variety of radiopharmaceuticals and techniques. Nowadays the gold standard radionuclide procedure, when an osteomyelitis is suspected, is represented by the use of radiolabelled leukocytes with either 99mTc-HMPAO or 111In-oxine. Methods: : In this review, we describe the correct acquisition and interpretation of white blood cell scintigraphy and we provide an overview of the existing literature data of the use of this technique in the infected diabetic foot. If images are correctly acquired, displayed and interpreted, this modality reaches very high diagnostic accuracy (>95%) in detecting osteomyelitis and it allows the differential diagnosis with a soft tissue infection or inflammation. Single-photon emission computed tomography/computed tomography (SPECT/CT) in addition to planar images is mandatory to determine the extent and exact location of the infective process in both fore foot and midhint foot. With the addition of bone marrow scintigraphy using radiolabelled nanocolloids, radiolabelled white blood cell scintigraphy is also able to differentiate between Charcot neuroarthropathy and osteomyelitis, which is a challenge in the evaluation of diabetic foot. Radiolabelled anti-granulocyte monoclonal antibodies and their fragments can also be used instead of white blood cells although there is a limited experience on their usefulness in diabetic foot infection.

International audience; The project "Metrology for molecular radiotherapy" is a collaborative European project initiated to bring together expertize in ionizing radiation metrology and nuclear medicine research. This project deals with the development of personalized dosimetry to individual patients who are undergoing molecular radiotherapy (also known as targeted radionuclide therapy). The general aim is to provide a metrological traceability to primary standards for individual dosimetry in the case of molecular radiotherapy. In particular, one objective is the standardization of Y-90-labeled resin microspheres SIR-Spheres (Sirtex, Sydney, Australia) used for the treatment of liver cancer by radioembolization. The present paper describes the primary measurements carried out using the Triple to Double Coincidence Ratio (TDCR) method applied after the complete dissolution of the SIR-Spheres in the Sirtex vial. A method for the dissolution was developed to optimize the homogeneity of the solution to enable the primary measurements based on Cherenkov and liquid scintillation counting. A comprehensive description of the protocol implemented for the microsphere dissolution is reported. First calibration factors obtained with the reference ionization chambers at LNE-LNHB are also given.

Ga-68-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of Ga-68-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of I-125-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of Ga-68-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR 5 1.95 +/- 0.51 vs. 1.22 +/- 0.25 and mean TBR 5 1.24 +/- 0.38 vs. 0.96 +/- 0.37, respectively; P

International audience; Due to their stability and reproducibility, re-entrant pressurized ionization chambers (also called radionuclide calibrators) are widely used for activity measurements in nuclear medicine services as well as in national metrology institutes to maintain reference standards. Generally, these secondary instruments yield accurate activity measurements for gamma-emitting radionuclides. Ionization chambers are easy to use and thus well-adapted to guarantee the metrological traceability between national metrology institutes and end-users. However, the reproducibility of calibration factors can be significantly impaired when measuring high-energy pure beta-emitters such as radiopharmaceuticals based on 90Y. This is because the bremsstrahlung emission contributing to the instrument response is strongly dependent on the geometry of the components surrounding the radioactive solution. The present article describes a new design based on pulse counting to address this problem. It takes advantage of Cherenkov emission resulting from Compton scattering in transparent materials. The interest of Cherenkov counting is to obtain a low-sensitivity detector that enables direct measurements of high-activity solutions (at least up to 10 GBq for 90Y-microspheres in aqueous suspensions used in nuclear medicine). A simple design based on a geometry close to an ionization chamber used at LNHB (Vinten 671 type) is described. The feasibility in terms of detection efficiencies (lower than 10^-4for 90Y solutions) of the new radionuclide calibrator is investigated by Monte Carlo calculations using the Geant4 code.

Purpose: The rapid growth and usage of small animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is first to characterize the magnitude and spatial distribution of the scatter component in small animal PET imaging when scanning single and multiple rodents simultaneously and second to assess the relevance and evaluate the performance of scatter correction under similar conditions. Methods: The LabPET™ 8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape based and more realistic voxel based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small animal PET imaging evaluated in terms of image quality and quantitative accuracy. Results: A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single and multiple subject imaging. In the LabPET™ 8 scanner the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out of field of view (FOV) scatter fraction (SF) is 1.70 0.76 and 0.11 for lower energy thresholds of 250 350 and 400 keV respectively. The increase in SF ranged between 25 and 64 when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole body and rat whole body anatomical models were improved for multiple imaging studies following scatter correction. Conclusions: The magnitude and spatial distribution of the scatter component in small animal PET imaging of single and multiple subjects simultaneously were characterized and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies whereas its impact is insignificant in single mouse imaging. © 2013 World Molecular Imaging Society.

There has been a significant increase in the number of joint prosthesis replacements worldwide. Although relatively uncommon, complications can occur with the most serious being an infection. Various radiological and nuclear imaging techniques are available to diagnose prosthetic joint infections (PJI). In this review article, we describe the pathophysiology of PJI, the principles of nuclear medicine imaging and the differences between Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The value of nuclear medicine techniques for clinical practice is also discussed. Then we provide an overview of the most often used radionuclide imaging techniques that may be helpful in diagnosing prosthetic joint infection: the Ga-67-citrate, labelled white blood cells in vitro and in vivo (monoclonal antibodies directed against specific targets on the leukocytes), and F-18-fluorodeoxyglucose (F-18-FDG). We describe their working methods, the pitfalls, and the interpretation criteria. Furthermore, we review recent advances in imaging bacteria, a molecular imaging method that holds promises for the detection of occult infections. We conclude proposing two diagnostic flow-charts, based on data in the literature, that could help the clinicians to choose the best nuclear imaging method when they have a patient with suspicion of or with proven PJI.

There has been a significant increase in the number of joint prosthesis replacements worldwide. Although relatively uncommon, complications can occur with the most serious being an infection. Various radiological and nuclear imaging techniques are available to diagnose prosthetic joint infections (PJI). In this review article, we describe the pathophysiology of PJI, the principles of nuclear medicine imaging and the differences between Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The value of nuclear medicine techniques for clinical practice is also discussed. Then we provide an overview of the most often used radionuclide imaging techniques that may be helpful in diagnosing prosthetic joint infection: the (67)Ga-citrate, labelled white blood cells in vitro and in vivo (monoclonal antibodies directed against specific targets on the leukocytes), and (18)F-fluorodeoxyglucose ((18)F-FDG). We describe their working methods, the pitfalls, and the interpretation criteria. Furthermore, we review recent advances in imaging bacteria, a molecular imaging method that holds promises for the detection of occult infections. We conclude proposing two diagnostic flow-charts, based on data in the literature, that could help the clinicians to choose the best nuclear imaging method when they have a patient with suspicion of or with proven PJI.

Proceedings of the 20th International Conference on Radionuclide Metrology and its Applications (ICRM), 8-11 June 2015, Vienna, Austria. Organizer TU Wien. Editors Franz-Josef Maringer, Dirk Arnold, Uwe Wätjen.; International audience; The present paper addresses the calibration of well-type ionization chambers (ICs) used at LNE-LNHB as standard transfer instruments to calibrate hospitals in the case of SIR-Spheres $^{90}$Y resin microspheres (Sirtex, Australia). Developed for interventional oncology, this radiopharmaceutical is directly injected in the liver for cancer treatment via a selective internal radiation therapy. The present work was carried out in the framework of the European project “Metrology for molecular radiotherapy” (MetroMRT). As commonly performed in radionuclide metrology for radiopharmaceuticals, the objective is to ensure the metrological traceability of SIR-Spheres to hospitals. Preceding studies were focused on primary measurements of SIR-Spheres based on the TDCR (Triple to Double Coincidence Ratio) method, applied after the dissolution of the $^{90}$Y-labeled resin microspheres. As $^{90}$Y is a high-energy β$^-$-emitter, the IC response strongly depends on the transport of electrons in the radioactive solution and surroundings (vial, chamber liners and materials). The variability of the IC-response due to the geometry dependence is investigated by means of measurements and Monte Carlo simulations in the case of a Vinten IC. The aim of the present study was also to propose a reliable uncertainty for ICs calibrations for the standard transfer of SIR-Spheres to hospitals.

The aim of this study was to define, retrospectively, the utility to perform Tc-99m-EDDA/HYNIC-Tyr3-octreotide (Tc-99m-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which Tc-99m-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of Tc-99m-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 Tc-99m-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, Tc-99m-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comorbidities, such as dyslipidemia and metabolic syndrome. We have used whole-body PET/CT to characterize the biodistribution and dosimetry of a novel high-affinity, subtype-selective radioligand, F-18-MK-9470, in healthy male and female subjects. Methods: Eight nonobese subjects (5 men, 3 women; age, 22-54 y) underwent serial whole-body PET/CT for 6 h after a bolus injection of 251 +/- 25 MBq F-18-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-F-18-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide). Source organs were delineated 3-dimensionally using the combined morphologic and functional data. Residence times were derived from time-activity profiles using both the trapezoid rule and curve fitting. Individual organ doses and effective doses were determined using the OLINDA software package, with different approaches for gastrointestinal and urinary excretion modeling. Results: F-18-MK-9470 is taken up slowly in the brain, reaching a plateau at approximately 90-120 min after bolus injection and is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, small intestine, and liver are the organs with the highest absorbed dose (average: 159, 98, 87 and 86 mu Gy/MBq, respectively). The mean effective dose (ED) was 22.8 +/- 4.3 mu Sv/MBq, indicating relatively low intersubject variability and a mean value in the range of many commercially available F-18-labeled radiopharmaceuticals. Brain uptake was relatively high compared with that of existing central nervous system ligands for other receptors, between 3.2% and 4.9% of the injected dose. Conclusion: The estimated radiation bur-den of F-18-MK-9470 for PET CB1 receptor imaging shows relatively low variability between subjects and has an acceptable ED, which allows multiple serial cerebral scans of good image quality, while remaining within the risk category class II-b defined by the World Health Organization and the International Commission for Radiation Protection for a standard injected activity (185-370 MBq). ispartof: Journal of Nuclear Medicine vol:49 issue:3 pages:439-445 ispartof: location:United States status: published

1Nuclear Medicine Unit, Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Ospedale S. Andrea, “Sapienza” University, Via di Grottarossa 1035, 00189 Roma, Italy 2Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen University of Groningen, Hanzeplein 1, 9700 RB Groningen, Netherlands 3Nuclear Medicine Department, Bichat-Claude Bernard Hospital and Paris Diderot University, 46 Rue Henri Huchard, 75018 Paris, France

Drug analysis and development with PET should fully exhaust the ability of this tomographic technique to quantify regional tracer concentrations in vivo. Data evaluation based on visual inspection or assessment of regional image contrast is not sufficient for this purpose since much of the information present in dynamically acquired data is not used by these approaches. Compartment modelling of dynamic PET data is generally the method of choice since it allows a quantitative assessment of the underlying pharmacokinetic parameters describing drug transport, metabolism and molecular interactions. We present here an overview of key issues of compartment modelling with specific attention to the assumptions underlying the various models and their limitations. We believe that a thorough understanding of the applicability of models is mandatory for the development, successful execution and analysis of quantitative PET studies. Otherwise, meaningful and interpretable results will often not be obtained.

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human-versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of F-18-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, F-18-FBPA and O-15-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human-versus mouse-derived biokinetic data. Moreover, the effect of using voxel-versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

International audience; Focusing optics operating in the soft gamma-ray photon energy range can advance a range of scientific and technological applications that benefit from the large improvements in sensitivity and resolution that true imaging provides. An enabling technology to this end is multilayer coatings. We show that very short period multilayer coatings deposited on super-polished substrates operate efficiently above 0.6 MeV. These experiments demonstrate that Bragg scattering theory established for multilayer applications as low as 1 eV continues to work well into the gamma-ray band. (C) 2014 Optical Society of America

Purpose: Positron emission tomography (PET) plays an important role in the diagnosis, staging, treatment, and surveillance of clinically localized diseases. Combined PET/CT imaging exhibits significantly higher sensitivity, specificity, and accuracy than conventional imaging when it comes to detecting malignant tumors in children. However, the radiation dose from positron-emitting radionuclide to the pediatric population is a matter of concern since children are at a particularly high risk when exposed to ionizing radiation. Methods: The authors evaluate the absorbed fractions and specific absorbed fractions (SAFs) of monoenergy photons/electrons as well as S-values of 9 positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124) in 48 source regions for 10 anthropomorphic pediatric hybrid models, including the reference newborn, 1-, 5-, 10-, and 15-yr-old male and female models, using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code. Results: The self-absorbed SAFs and S-values for most organs were inversely related to the age and body weight, whereas the cross-dose terms presented less correlation with body weight. For most source/target organ pairs, Rb-82 and Y-86 produce the highest self-absorbed and cross-absorbed S-values, respectively, while Cu-64 produces the lowest S-values because of the low-energy and high-frequency of electron emissions. Most of the total self-absorbed S-values are contributed from non-penetrating particles (electrons and positrons), which have a linear relationship with body weight. The dependence of self-absorbed S-values of the two annihilation photons varies to the reciprocal of 0.76 power of the mass, whereas the self-absorbed S-values of positrons vary according to the reciprocal mass. Conclusions: The produced S-values for common positron-emitting radionuclides can be exploited for the assessment of radiation dose delivered to the pediatric population from various PET radiotracers used in clinical and research settings. The mass scaling method for positron-emitters can be used to derive patient-specific S-values from data of reference phantoms. (C) 2013 American Association of Physicists in Medicine.

Purpose: Positron emission tomography (PET) plays an important role in the diagnosis, staging, treatment, and surveillance of clinically localized diseases. Combined PET/CT imaging exhibits significantly higher sensitivity, specificity, and accuracy than conventional imaging when it comes to detecting malignant tumors in children. However, the radiation dose from positron-emitting radionuclide to the pediatric population is a matter of concern since children are at a particularly high risk when exposed to ionizing radiation. Methods: The authors evaluate the absorbed fractions and specific absorbed fractions (SAFs) of monoenergy photons/electrons as well as S-values of 9 positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124) in 48 source regions for 10 anthropomorphic pediatric hybrid models, including the reference newborn, 1-, 5-, 10-, and 15-yr-old male and female models, using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code. Results: The self-absorbed SAFs and S-values for most organs were inversely related to the age and body weight, whereas the cross-dose terms presented less correlation with body weight. For most source/target organ pairs, Rb-82 and Y-86 produce the highest self-absorbed and cross-absorbed S-values, respectively, while Cu-64 produces the lowest S-values because of the low-energy and high-frequency of electron emissions. Most of the total self-absorbed S-values are contributed from non-penetrating particles (electrons and positrons), which have a linear relationship with body weight. The dependence of self-absorbed S-values of the two annihilation photons varies to the reciprocal of 0.76 power of the mass, whereas the self-absorbed S-values of positrons vary according to the reciprocal mass. Conclusions: The produced S-values for common positron-emitting radionuclides can be exploited for the assessment of radiation dose delivered to the pediatric population from various PET radiotracers used in clinical and research settings. The mass scaling method for positron-emitters can be used to derive patient-specific S-values from data of reference phantoms. (C) 2013 American Association of Physicists in Medicine.

Ziel: Zur Darstellung von Integrin αvβ3 von Tumoren oder Tumorneugefäßen wählten wir das zyklische Bindungspeptid Arg-Gly-Asp-D-Tyr-Lys (RGDyK) gekoppelt an NODAGA zur Markierung mit 68Ga. Methoden: NODAGA-RGDyK (ABX) wurde mit dem 68Ga-Eluat des 68Ge-Generators IGG100 markiert mit der Prozessoreinheit PharmTracer. Bioverteilungen wurden in weiblichen Hsd-Mäusen 10, 30, 60 und 90 min nach i.v.-Injektion von 68Ga-NODAGA-RGDyK gemessen und als OLINDA-Dosimetrie auf den Menschen projiziert. In SCID-Mäusen, die A431 und andere Tumoren trugen, wurde die Tumoraufnahme mit microPET und Bioverteilungen studiert. Ergebnisse: Die effektive Halbwertszeit von 68Ga-NODAGA-RGDyK war ~25 min im Ganzkörper und den meisten Organen außer Leber und Milz, für die eine stabile Aufnahme gemessen wurde. Die für Frauen und Männer berechnete effektive Dosis (ED) war 0.012 bzw. 0.016 mSv/MBq mit der Annahme eines Blasenleerungsintervalls von 0.5 h. Mit dynamischem PET wurde eine rasche A431-Tumoraufnahme innerhalb von 10 Minuten beobachtet, gefolgt von einem langsamen Abfluss. Bioverteilungen zeigten eine A431-Tumoraufnahme von 68Ga-NODAGA-RGDyK von 3.4±0.4 und 2.7±0.3%ID/g nach 1 bzw. 2 Stunden. Ähnliche Tumoranreicherungen in der Maus wurden in einem Maus- und Humanbrustkrebs gemessen sowie in humanem Ovarialkrebs. Co-Injektion mit einer Überdosis (5 mg/kg) unmarkiertem NODAGA-RGDyK mit dem Radiopharmazeutikum reduzierte die Tumoraufnahme auf 0.23±0.01%ID/g nach 1 Stunde, jedoch wurde eine ähnlich reduzierte Aufnahme auch in andern normalen Organen beobachtet. Wenn unmarkiertes Peptid 15 min nach 68Ga-NODAGA-RGDyK injiziert wurde, verminderte sich die Aufnahme besonders in Tumor und Nebennieren. Diese Beobachtung kann im Vergleich zu anderen Normalgeweben als unterschiedliches Bindungsverhalten gedeutet werden. Schlussfolgerung: NODAGA-RGDyK konnte zuverlässig mit 68Ga markiert werden und zeigte für Menschen eine vorhergesagte ED von 0.014 mSv/MBq. Die Tumoranreicherung war schnell und signifikant. Sie wurde aus Tumor und Nebennieren durch nachgespritztes, unmarkiertes NODAGA-RGDyK in ähnlicher Weise verdrängt. Aim: To visualize neovasculature and/or tumour integrin αvβ3 we selected the binding moiety Arg-Gly-Asp-D-Tyr-Lys (RGDyK) coupled to NODAGA for labeling with 68Ga. Methods: NODAGA-RGDyK (ABX) was labeled with the 68Ga eluate from the 68Ge generator IGG100 using the processor unit PharmTracer. Biodistribution was measured in female Hsd mice sacrificed 10, 30, 60 and 90 min after i.v. injection of 68Ga-NODAGA-RGDyK for OLINDA dosimetry extrapolated to humans. Tumour targeting was studied in SCID mice bearing A431 and other tumour transplants using microPET and biodistribution measurements. Results: Effective half-life of 68Ga-NODAGA-RGDyK was ~25 min for total body and most organs except liver and spleen that showed stable activity retention. With a bladder voiding interval of 0.5 h the calculated effective dose (ED) was 0.012 and 0.016 mSv/MBq for males and females, respectively. Rapid uptake within 10 min was observed in A431 tumours with dynamic PET followed by a slow release. Biodistribution measurements showed a 68Ga-NODAGA-RGDyK uptake in A431 tumours of 3.4±0.4 and 2.7±0.3%ID/g at 1 and 2 h, respectively. Similar uptakes were observed in a mouse and human breast and ovarian cancer xenografts. Co-injection of excess (5 mg/kg) unlabeled NODAGA-RGDyK with the radiotracer reduced tumour uptake at one hour to 0.23±0.01%ID/g, but similarly decreased uptake in normal organs as well. When unlabeled peptide was injected 15 min after 68Ga-NODAGA-RGDyK, uptake diminished particularly in tumour and adrenals, suggestive of a different binding mode compared with other normal tissues. Conclusion: NODAGA-RGDyK was reliably labeled with 68Ga and revealed a predicted ED of 0.014 mSv/MBq. Tumour uptake was rapid and significant and was chased with unlabeled RGDyK in a similar manner as adrenal uptake.

This study aimed to estimate the radiation absorbed doses to normal tissues and tumor lesions during radioimmunotherapy with (177)Lu-cG250. Serial planar scintigrams after injection of (111)In-cG250 or (177)Lu-cG250 in patients with metastasized renal cell carcinoma were analyzed quantitatively. The estimated radiation doses were correlated with observed hematologic toxicity. In addition, the accuracy of the predicted therapeutic absorbed doses, based on diagnostic (111)In-cG250 data, were determined.METHODS:Twenty patients received a diagnostic tracer activity of (111)In-cG250 (185 MBq), followed by radioimmunotherapy with (177)Lu-cG250. The administered activity of (177)Lu-cG250 was escalated by entering 3 patients at each activity level starting at 1,110 MBq/m(2), with increments of 370 MBq/m(2). After each diagnostic and therapeutic administration, whole-body scintigraphic images and pharmacokinetic data were acquired. Hematologic toxicity was graded using the Common Toxicity Criteria, version 3.0. Diagnostic (111)In-cG250 data were used to simulate (177)Lu and (90)Y data by correcting for the difference in physical decay. Absorbed doses were calculated for the whole body, red marrow, organs, and tumor metastases for the therapeutic (177)Lu-cG250, simulated (177)Lu-cG250, and simulated (90)Y-cG250 data.RESULTS:Observed hematologic toxicity, especially platelet toxicity, correlated significantly with the administered activity (r = 0.85), whole-body absorbed dose (r = 0.65), and red marrow dose (r = 0.62 and 0.75). An inverse relationship between the mass and absorbed dose of the tumor lesions was observed. Calculated mean absorbed doses were similar for the simulated and measured (177)Lu-cG250 data. Absorbed doses (whole body and red marrow) based on the simulated (177)Lu-cG250 data correlated with the observed platelet toxicity (r = 0.65 and 0.82). The tumor-to-red marrow dose ratio was higher for radioimmunotherapy with (177)Lu-cG250 than for radioimmunotherapy with (90)Y-cG250, indicating that (177)Lu has a wider therapeutic window for radioimmunotherapy with cG250 than (90)Y.CONCLUSION:In patients with metastasized renal cell carcinoma, hematologic toxicity after treatment with (177)Lu-cG250 can be predicted on the basis of administered activity and whole-body and red marrow-absorbed dose. Diagnostic (111)In-cG250 data can be used to accurately predict absorbed doses and myelotoxicity of radioimmunotherapy with (177)Lu-cG250. These estimations indicate that in these patients, higher radiation doses can be guided to the tumors with (177)Lu-cG250 than with (90)Y-cG250.

Purpose: To evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin - single photon emission computer tomography (T-SPECT). Materials and methods: We studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263). Results: Abnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 +/- 3.5 vs 2.6 +/- 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 +/- 3.0 vs 2.6 +/- 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent. Conclusion: The study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences. Radiation Oncology

TO THE EDITOR: In a recent issue of The Journal Nuclear Medicine, 2 interesting papers on PET detection of epidermal growth factor receptor (EGFR) in cancer were published ( [1][1],[2][2] ). Liu et al. reported the potential of 11C-PD153035 for the imaging of EGFR expression in humans, especially in

The excitation functions of proton induced reactions on Sc targets (100% Sc-45), leading to the formation isotopes K-43, Sc-43, Sc-44m, Sc-44g and Ti-44 were studied by the stacked foil activation technique up to 37 MeV. High-resolution gamma-spectrometry measurements were performed on an HPGe detector in order to determine the activity of the irradiated SC2O3 pellets and Ti monitor foils. The reaction cross-sections were measured from their respective thresholds up to E-P = 36.4 MeV and were compared with previous values reported in literature. Possible batch yields and optimal irradiation parameters for generator Ti-44-Sc-44g in high current accelerators are discussed. (C) 2009 Elsevier B.V. All rights reserved.

In its theoretical part, this work is concerned with the equipment and devices used within the nuclear-medicine quality assurance programme, in particular gamma-camera, as well as acceptance and operational tests the purpose of which is to verify parameter compliance in reference to the values determined during the equipment acceptance tests. Special attention is paid to the signal detection quality, activity measurement correctness and precision, the factors influencing the same and the measurement errors. To avoid incorrect interpretation of erroneous measurements results, continuous quality control is required for the instruments intended to detect ionising radiation. Another subject of the theoretical part is quality of the visualisation technique where the poor quality of the final image may result from incorrect setting and/or failures of the visualisation equipment. The final section of the theoretical part reviews the existing fixtures and radiation sources used in calibration and testing of the image properties of scintillation cameras {--} the so-called phantoms. The target of this work is verification of the basic parameters stability of two gamma-cameras and demonstration of the importance of regular scintillographic measurements for the medical examination quality. The practical part of this work is focused on comparison regarding parameter stability of two Siemens SPECT cameras, model E.CAM of different manufacturing dates. Subject to verification were the basic equipment parameters normally tested within the standard operation stability and quality assurance programmes. The measured values have been arranged in tables and shown in graphs, and subject to statistical processing. The results of this work will be used in working out the operational standards for the nuclear medicine department of Faculty Hospital in Lochotín in Plzeň, and may serve as reference data in decision on replacement of outdated equipment and devices.

The aim of this study was to define, retrospectively, the utility to perform Tc-99m-EDDA/HYNIC-Tyr3-octreotide (Tc-99m-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which Tc-99m-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of Tc-99m-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 Tc-99m-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, Tc-99m-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

Small-animal positron emission tomography (PET) and single photon emission tomography (SPECT) are invaluable tools in drug discovery and in assessing novel therapeutic agents. In a typical small-animal PET or SPECT imaging session, a radiopharmaceutical is administered and the kinetics of its distribution tracked. Whereas the PET and SPECT protocols for the radiotraceras used in clinical practice are well established, at least for the radiotracers that are used in clinical practice, the acquisition, reconstruction and data analysis procedures applied in small rodents are heterogeneous among centres, often being determined by the scanner characteristics and by the animal models and anaesthesia procedures used in the laboratory. This review, intended to serve as a guide to preclinical PET and SPECT experiments, aims to familiarise the reader with the aspects of PET and SPECT that pertain to in vivo preclinical acquisitions and, in particular, with the technical and methodological know-how that is needed for better application of radionuclide imaging techniques in preclinical cancer research.