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Funding Information: On behalf of the Public and Community Oversight Group (PCOG) of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards: Ian Wright; John Phipps; Colette Kelly; Robert Goundry; Eve Smyth; Andrew Wood; Paul Dale (also of the Scottish Environment Protection Agency). On behalf of the Society and College of Radiographers Patient Advisory Group: Lynda Johnson; Philip Plant; Michelle Carmichael – Specialist Senior Staff Nurse Guy's and St Thomas’ NHS Foundation trust.

Objectives Bedside radiographs are usually obtained gridless, without a physical scatter correction grid because of several limitations. Therefore, multiple manufacturers of mobile radiography systems provide the possibility to apply scatter correction software (SC SW) on those images. The purpose of this study was to characterize different series of radiographs-gridless, SC SW, and physical grid-with an image quality assessment algorithm (IQAA). Furthermore, we investigated the potential dose reduction and the correlation between the output of the IQAA and the human observers. Materials and Methods We obtained different series of radiographs with an anthropomorphic phantom (multipurpose chest phantom N1 "Lungman," Kyoto Kagaku, Kyoto, Japan). All radiographs were obtained with flat-panel detectors of 5 different manufacturers in a wall bucky system. An IQAA to analyze the radiographs was implemented in our department but was originally developed by the research group of the Duke University Medical Center. Seven physical quantities were calculated by the IQAA: rib-lung contrast (RLcontrast), subdiaphragm-lung contrast (SLcontrast), lung detail (L-detail), mediastinum detail (M-detail), lung noise (L-noise), mediastinum noise (M-noise), and rib-lung sharpness (RLsharpness). In a proof of concept, the results of the IQAA were validated by 3 experienced radiologists. Results Regression coefficients (b) of the linear regression model indicate that the human observer results correlate well with the IQAA (b >= 0.89, R-2 >= 0.83). All manufacturers have SC SW that increases the 7 physical quantities of the gridless images. However, several manufacturers have SC SW that increases the physical metrics to the same level as the physical grid images. The SC SW radiographs obtained with a reduced tube load have an increased level of contrast, detail, sharpness, and noise compared with the gridless images obtained with the higher tube load. Conclusions We have proven in a proof of concept that the originally developed IQAA can be used to characterize different series of images of different manufacturers. Based on the physical quantities, SC SW increases the contrast, detail, sharpness, and noise. The experimental results in this study assume a patient dose reduction could be possible when SC SW is applied.

Objectives We evaluated the different Virtual Grid software ratios (Fujifilm, Tokyo, Japan) on gridless clinical chest radiographs with visual grading analysis (VGA). In addition, we investigated the 2 image quality assessment algorithms (IQAAs). Materials and Methods Gridless chest radiographs of 50 different intensive care unit patients were collected and afterward processed with Virtual Grid software. Different software (SW) grid ratios-6:1, 10:1, 13:1, 17:1, and 20:1-were applied to investigate the image quality (IQ) improvement. Image quality improvement was assessed by 4 radiologists in a relative VGA study where the reference image was processed with SW grid ratio of 10:1. One of the IQAAs used to analyze the radiographs was implemented in our department but was originally developed by the research group of the Duke University Medical Center. A general IQ score (IQS) was calculated based on contrast, detail, and noise. Another IQAA-NIQE (naturalness image quality evaluator)-available in Matlab (MATLAB Research R2019b; the MathWorks, Inc) was evaluated. Both methods were compared with VGA. Results Visual grading analysis scores of gridless radiographs are significantly lower (P < 0.001). Image quality increases with increasing SW grid ratios, up to grid ratio of 17:1. However, some anatomical structures-spine and ribs-are negatively affected by the higher grid ratios. A correlation coefficient of 0.99 between the VGA and the IQS was observed. The correlation coefficient between VGA and NIQE was 1.00. Conclusions Virtual Grid with SW grid ratio of 6:1 improves the IQ of gridless chest bedside radiographs. The grid ratios 17:1 and 20:1 should be considered carefully as the SW negatively affects parts of the ribs and spine. Therefore, grid ratios up to 13:1 can be advised. The IQAAs are promising and could be used to detect differences in IQ when different scatter correction SW settings are used.

Background Personal radiation protective equipment (PRPE) such as lead aprons, vests, skirts and thyroid shields minimize radiation exposure of operators using ionizing radiation. However, PRPE might be prone to cracks and tears in the attenuating layer of the garments which results in inadequate radiation protection and increased operator dose. Currently, there are no uniform guidelines regarding regular inspection and/or rejection criteria of PRPE. Purpose This study aims to investigate the prevalence, qualification and quantification of PRPE integrity during a longitudinal follow-up. Methods All PRPE of a large, general hospital was yearly evaluated in the period 2018–2020. The equipment was inspected on a tele-operated X-ray table and cracks and tears were qualified and quantified using an X-ray opaque ruler. Rejection criteria of Lambert & McKeon were applied to accept or reject further use of the PRPE. In brief, all pieces, except for thyroid shields, with a total defect area larger than 670mm2 are rejected. For tears, specifically at the position of the gonads, an extra rejection criterion of 15mm2 is defined. For thyroid shields, the rejection criterion is set to 11mm2. Results In the 3-year follow-up period, a total of 915 PRPE were evaluated. 43.3% of PRPE showed tears and 29.3% needed to be rejected based on the Lambert & McKeon criteria. More specifically, in 2018, 2019 and 2020, respectively, 17.4%, 16.9% and 21.2% were rejected. In the attached figure, typical examples of visualized defects are represented. The median tear area (interquartile range) was 12 (30) mm2. Remarkably, of 195 newly registered PRPE, 8.7% showed tears in the first year of use of which 88.2% needed to be rejected. In the latter case, the median tear area (interquartile range) was 40 (50) mm2. Information regarding purchase date and size is missing in respectively 45.5% and 50.7% of the cases. Additionally, 13.7% lacked information regarding lead equivalency. Conclusion PRPE are prone to tears and cracks. Up to 40% of PRPE showed tears and cracks resulting in nearly 20% rejections. Newly purchased PRPE are not guaranteed to remain free of cracks and tears in the first year of use. These results urge the importance for regular X-ray based integrity analysis of PRPE. Funding Acknowledgement Type of funding sources: None.

Micro-CT imaging is an increasingly popular tool in the internal investigation of objects and materials. However, as an X-ray based technique, a potentially harmful radiation dose is deposited in the sample during the measurement. In (non small-animal) micro-CT imaging one is dealing with a strong variation in measurement systems and settings, resulting in many different acquisition circumstances and the absence of standard imaging protocols. Therefore, the deposited dose is rarely studied for micro-CT applications. This research aimed at developing a fast simulation technique to predict the dose associated with micro-CT scanning. Its performance is compared with that of two different Monte Carlo simulation tools and with a straight forward approach to estimate an upper limit for the dose. The fast simulation method, obtaining a dose estimation based on the energy absorption coefficient, is much faster than the Monte Carlo simulations, and the results are accurate within 30%. This enables us to predict the dose for a known sample and a known scanner setup, without complex Monte Carlo simulations and will allow researchers to avoid radiation damage or unwanted radiation induced effects, an increasingly important concern in 3D and 4D micro-CT scanning.

Prostate specific membrane antigen (PSMA) is highly overexpressed in prostate cancer. Many PSMA analogue radiotracers for PET/CT imaging of prostate cancer staging have been developed such as 68Ga-PSMA-11. This radiotracer has achieved good results in multiple clinical trials, but because of superior imaging characteristics of 18F-fluoride, 18F-PSMA-11 was developed. The aim of this study was to evaluate the safety of administration and the radiation dosimetry of 18F-PSMA-11. METHODS: Six patients (age 62-68y, mean 66 ± 2y) with suspected prostate cancer recurrence after previous treatment were administered 2 MBq/kg bodyweight 18F-PSMA-11 followed by PET/CTlow-dose imaging at 0, 20, 50, 90 and 300 min post injection (p.i.). To evaluate the safety of administration, vital parameters were monitored. To assess toxicity, full blood count and biochemical parameters were determined. According to the latest ICRP recommendations, radiation dosimetry analysis was performed using IDAC-Dose 2.1. For blood activity measurement, small samples of venous blood were collected at various timepoints p.i. The unbound 18F-fluoride fraction was determined in plasma 20, 50 and 90 min after administration to evaluate the defluorination rate of 18F-PSMA-11. RESULTS: After injection, 18F-PSMA-11 was rapidly cleared from the blood. 29.0 ± 5.9% of the activity was excreted in urine at 5h p.i. The free 18F fraction in plasma increased from 9.7 ± 1.0% 20 min p.i. to 22.2 ± 1.5% 90 min p.i. The highest tracer uptake was observed in kidneys, bladder, spleen and liver. No study drug related adverse events were observed. The calculated mean effective dose was 12.8 ± 0.6 µSv/MBq. CONCLUSION:18F-PSMA-11 can be safely administered and results in a mean effective dose of 12.8 ± 0.6 µSv/MBq. Therefore, the total radiation dose is lower compared to other PSMA PET agents and in the same range of 18F-DCFPyL.

Background Dual axis rotational coronary angiography ( DARCA ) reduces radiation exposure during coronary angiography on older x‐ray systems. The purpose of the current study is to quantify patient and staff radiation exposure using DARCA on a modality already equipped with dose‐reducing technology. Additionally, we assessed applicability of 1 dose area product to effective dose conversion factor for both DARCA and conventional coronary angiography ( CCA ) procedures. Methods and Results Twenty patients were examined using DARCA and were compared with 20 age‐, sex‐, and body mass index–matched patients selected from a prior study using CCA on the same x‐ray modality. All irradiation events are simulated using PCXMC ( STUK , Finland) to determine organ and effective doses. Moreover, for DARCA each frame is simulated. Staff dose is measured using active personal dosimeters (DoseAware, Philips Healthcare, The Netherlands). With DARCA , median cumulative dose area product is reduced by 57% (ie, 7.41 versus 17.19 Gy·cm 2 ). Effective dose conversion factors of CCA and DARCA are slightly different, yet this difference is not statistically significant. The occupational dose at physician's chest, leg, and collar level are reduced by 60%, 56%, and 16%, respectively, of which the first 2 reached statistical significance. Median effective dose is reduced from 4.75 mSv in CCA to 2.22 mSv in DARCA procedures, where the latter is further reduced to 1.79 mSv when excluding ventriculography. Conclusions During invasive coronary angiography, DARCA reduces radiation exposure even further toward low‐dose values on a system already equipped with advanced image processing and noise reduction algorithms. For both DARCA and CCA procedures, using 1 effective dose conversion factor of 0.30 mSv·Gy −1 ·cm −2 is feasible.

INTRODUCTION Cardiac catheterization procedures result in high patient radiation exposure and corresponding staff doses are reported to be among the highest for medical staff. The purpose of current randomized controlled study was to quantify the potential radiation dose reduction for both patient and staff, enabled by recent X-ray technology. This technology is equipped with advanced image processing algorithms, real-time dose monitoring, and an acquisition chain optimized for cardiac catheterization applications. METHODS A total of 122 adult patients were randomly assigned to one of two cath labs, either the reference X-ray modality (Allura Xper FD10, Philips Healthcare, the Netherlands) or the new X-ray system (AlluraClarity FD20/10 Philips Healthcare, the Netherlands). Exposure parameters and staff dosimeter readings were recorded for each exposure. Technical measurements were performed to define the radiation scatter behavior. RESULTS With the newer equipment, patient radiation dose is reduced (as total dose-area product) by 67% based on geometric means with 95%CI of 53%, 77% for diagnostic and interventional procedures. The C-arm and leg dosimeter readings were both reduced with 65% (P

Prostate-specific membrane antigen (PSMA) is highly overexpressed in prostate cancer. Many PSMA analog radiotracers for PET/CT prostate cancer staging have been developed, such as

On 5 December 2013 the European Council promulgated Directive 2013/59/EURATOM. This Directive is important for Medical Physicists and Medical Physics Experts as it puts the profession on solid foundations and describes it more comprehensively. Much commentary regarding the role and competences has been developed in the context of the European Commission project “European Guidelines on the Medical Physics Expert” published as Radiation Protection Report RP174. The guidelines elaborate on the role and responsibilities under 2013/59/EURATOM in terms of a mission statement and competence profile in the specialty areas of Medical Physics relating to medical radiological services, namely Diagnostic and Interventional Radiology, Radiation Oncology and Nuclear Medicine. The present policy statement summarises the provisions of Directive 2013/59/EURATOM regarding the role and competences, reiterates the results of the European Guidelines on the Medical Physics Expert document relating to role and competences of the profession and provides additional commentary regarding further issues arising following the publication of the RP174 guidelines.

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

International audience; The “intended purpose” in all therapeutic exposures is treatment efficacy against malignant disease. The optimization principle (as low as reasonably achievable, ALARA) of article 56, when applied in a therapy situation, states that absorbed doses to nontarget tissues should be kept reasonably low, but not so low as to lose efficacy. We think that this applies above all to the fight against life-threatening cancer. As a consequence, we believe that to adhere to the optimization principle in oncological patients, nuclear medicine therapy should be based on individualized dosimetry.

Background: Biologicals directed against tumour necrosis factor (TNF) have proven their efficacy in the treatment of spondyloarthritis and rheumatoid arthritis. We present a radiolabelling method for certolizumab pegol (CZP), a commercially available humanized Fab'-fragment directed against TNF. A biodistribution and dosimetry study was conducted. Tc-S-HYNIC CZP was synthesized. The in vitro TNF neutralizing activity was tested by exposing L929s-cells to various concentrations 99mTc-S-HYNIC CZP and measuring TNF-induced cytotoxicity. For biodistribution and dosimetry, WB images and blood and urine sampling were performed up to 24 h pi. Cumulative activities were estimated using mono-exponential fitting, and organ doses were estimated using OLINDA/EXM. The effective dose was calculated using the International Commission on Radiological Protection 103 recommendations. The uptake of the tracer in the peripheral joints was assessed visually and semiquantitatively. Results: In vitro tests showed blocking of TNF cytotoxicity by the Tc-99m-S-HYNIC CZP formulation comparable to the effect obtained with the unlabelled CZP with or without the HYNIC linker. We analysed eight patients with rheumatoid arthritis or spondyloarthritis. The highest mean absorbed organ doses were recorded for kidneys, spleen, and liver: 56 (SD 7), 34 (SD 6), and 33 (SD 7) mu Gy/MBq. The effective dose was 6.1 (SD 0.9) mSv for a mean injected activity of 690 (SD 35) MBq. The urinary excretion was 15.1% (SD 8.1) of the IA at 22.5 h. Blood analysis yielded a distribution half-life of 1.2 h (SD 1.5) and an elimination half-life of 26.9 h (SD 2.7). Visual analysis of the scans revealed marked tracer accumulation in the clinically affected peripheral joints. In addition, there was a statistically significant higher uptake of the tracer in the swollen joints (median uptake ratio compared to background of 3.3 in rheumatoid arthritis and 2.4 in peripheral spondyloarthritis) compared to clinically negative joints (respectively 1.3 and 1.6). Conclusions: We present a radiolabelling technique for CZP, a Fab'-fragment directed against TNF and currently used as a therapeutic agent in rheumatology. An effective dose of 6.1 mSv (SD 0.9) was estimated. We confirmed the uptake of this new radiopharmaceutical in clinically affected peripheral joints.

Purpose To assess the potential dose reduction to the thyroid and breasts in chest CT, using organ-based tube-current modulation (OBTCM). Posterior organs in the field of view were analyzed and overall lifetime attributable risk (LAR) of cancer induction and mortality was evaluated. Methods With OBTCM, the exposure is lower when the X-ray tube passes over the anterior surface of the patient. In this way, the breast doses can be limited. However, to preserve image quality, the total exposure during one rotation has to be equal to the exposure of scans without OBTCM enabled. Therefore, the tube-current is higher during posterior projections. In this study (Jan 2015–Dec 2016), the location of the breasts with respect to the reduced tube-current zone was determined. Using Monte-Carlo simulations, patient-specific dose distributions of chest CT scans were calculated for 50 female patients (mean age 53.7 y ± 17.5, range 20–80 y). The potential dose reduction of OBTCM was assessed. In addition, simulations of clinical OBTCM scans were made for 17 female patients (mean age 43.8 y ± 17.1 y, range 20–69 y). LAR of cancer incidence and mortality was estimated according to BEIR-VII. Image quality (IQ) between standard and OBTCM scans was compared. Results No women had all breast tissue within the reduced tube-current zone. Clinical observed dose reductions were 18% (thyroid) and 9% (breasts) whereas lung, liver and kidney doses were 17%, 11% and 26% higher. Overall, LAR for cancer incidence was not significantly different (p = .06) between conventional and OBTCM scanning. IQ improved with OBTCM (p Conclusions The potential benefit of OBTCM to the female breast in chest CT is overestimated due to a limited reduced tube-current zone; despite a 9% dose reduction to the female breast, posterior organs will absorb up to 26% more radiation, resulting in no reduction of radiation induced malignancies.

The last years, the clinical interest in quantitative SPECT/CT imaging is increasing. Especially in the rapidly growing field of radionuclide therapy, quantitative imaging is essential to provide nuclear medicine physicians with accurate dosimetric data. As a result, manufacturers now focus on producing SPECT/CT systems that are intrinsically quantitative. SPECT quantification is more challenging than PET quantification. In fact, the correction for photon absorption is relatively straightforward to apply in PET. In addition, in SPECT, we need to consider a variety of radionuclides with different photon energies and energy windows, different collimators and the potential for drifts in performance due to the greater number of moving parts in a SPECT system. With SPECT/CT, the coregistered CT data provide accurate information on the density of the body tissues, which can be used in algorithms that correct for photons that have been Compton-scattered or attenuated within the body. State-of-the-art reconstruction techniques are based on statistical iterative methods such as the ordered-subset maximum-likelihood expectation maximization algorithm (OSEM). In this approach, the physical characteristics of the acquisition process can be completely modeled in the reconstruction. In this presentation, an overview of all factors affecting SPECT image quantification will be presented. The latest developments to achieve quantitative SPECT/CT reconstruction will be discussed, together with calibration issues to finally obtain radioactivity concentrations per unit volume (kBq/ml).

Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111 MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24 h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT4) and for the thyroid to salivary gland ratio with sodium pertechnetate γ-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT4 and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.

Background: The first aim of this study was to evaluate the correlation between clinical and physical-technical image quality applied to different strengths of iterative reconstruction in chest CT images using Thiel cadaver acquisitions and Catphan images. The second aim was to determine the potential dose reduction of iterative reconstruction compared to conventional filtered back projection based on different clinical and physical-technical image quality parameters. Methods: Clinical image quality was assessed using three Thiel embalmed human cadavers. A Catphan phantom was used to assess physical-technical image quality parameters such as noise, contrast-detail and contrast-to-noise ratio (CNR). Both Catphan and chest Thiel CT images were acquired on a multislice CT scanner at 120 kVp and 0.9 pitch. Six different refmAs settings were applied (12, 30, 60, 90, 120 and 150refmAs) and each scan was reconstructed using filtered back projection (FBP) and iterative reconstruction (SAFIRE) algorithms (1,3 and 5 strengths) using a sharp kernel, resulting in 24 image series. Four radiologists assessed the clinical image quality, using a visual grading analysis (VGA) technique based on the European Quality Criteria for Chest CT. Results: Correlation coefficients between clinical and physical-technical image quality varied from 0.88 to 0.92, depending on the selected physical-technical parameter. Depending on the strength of SAFIRE, the potential dose reduction based on noise, CNR and the inverse image quality figure (IQF(inv)) varied from 14.0 to 67.8 %, 16.0 to 71.5 % and 22.7 to 50.6 % respectively. Potential dose reduction based on clinical image quality varied from 27 to 37.4 %, depending on the strength of SAFIRE. Conclusion: Our results demonstrate that noise assessments in a uniform phantom overestimate the potential dose reduction for the SAFIRE IR algorithm. Since the IQF(inv) based dose reduction is quite consistent with the clinical based dose reduction, an optimised contrast-detail phantom could improve the use of contrast-detail analysis for image quality assessment in chest CT imaging. In conclusion, one should be cautious to evaluate the performance of CT equipment taking into account only physical-technical parameters as noise and CNR, as this might give an incomplete representation of the actual clinical image quality performance.

Purpose: To investigate the association between six transforming growth factor β1 gene ( TGFβ1 ) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGFβ1 . Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions ( p = 0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients. Conclusions: The present study shows that homozygous variant TGFβ1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT.

Objectives The purpose of this study was to quantify the reduction in patient radiation dose during coronary angiography (CA) by a new X-ray technology, and to assess its impact on diagnostic image quality. Background Recently, a novel X-ray imaging technology has become available for interventional cardiology, using advanced image processing and an optimized acquisition chain for radiation dose reduction. Methods 70 adult patients were randomly assigned to a reference X-ray system or the novel X-ray system. Patient demographics were registered and exposure parameters were recorded for each radiation event. Clinical image quality was assessed for both patient groups. Results With the same angiographic technique and a comparable patient population, the new imaging technology was associated with a 75% reduction in total kerma-area product (KAP) value (decrease from 47 Gycm2 to 12 Gycm2, P

During interventional cardiology procedures patient and staff are exposed to X-ray radiation. Minimizing radiation dose is a crucial part of quality care. This study quantifies the radiation dose reduction for patient and staff enabled by a novel X-ray imaging technology using advanced real-time

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained. Electronic supplementary material The online version of this article (doi:10.1007/s00259-011-1904-z) contains supplementary material, which is available to authorized users.

Background— A better knowledge of patient x-ray dose and the associated radiation risk in pediatric interventional cardiology is warranted in view of the extensive use of x-rays and the higher radiosensitivity of children. In the present study, γ-H2AX foci were used as a biomarker for radiation-induced effects. Patient-specific dose was assessed and radiation risks were estimated according to the linear-no-threshold model, commonly used in radiation protection, and the γ-H2AX foci data. Methods and Results— In 49 pediatric patients (median age, 0.75 years) with congenital heart disease who underwent cardiac catheterization procedures, blood samples were taken before and shortly after the procedure. γ-H2AX foci were determined in peripheral blood T lymphocytes. In each patient, a net increase in γ-H2AX foci, representing DNA double-strand breaks induced by interventional x-rays, was observed. In addition, a patient-specific Monte Carlo simulation of the procedure was performed, resulting in individual blood, organ, and tissue doses. Plotting of γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity. Median effective doses calculated according to the International Commission on Radiological Protection 60 and 103 publications are 5.6 and 6.4 mSv, respectively. The lifetime-attributable risk of cancer mortality was calculated from the linear-no-threshold model and the γ-H2AX foci data. This resulted in lifetime-attributable risk values of 1% and 4%, respectively, for the patient population under study. Conclusions— γ-H2AX foci as a biomarker for DNA damage indicate that radiation risk estimates according to the linear-no-threshold hypothesis are possibly underestimates. Great care should be taken to minimize and optimize patient radiation exposure.

Earlier reports described the preferential uptake of d-amino acids in tumor-bearing mice. Moreover, it was shown that in tumor cells in vitro the L-amino acid transporter system seemed to lack stereospecificity. Because of the successful results with 123/125I-2-iodo-L-phenylalanine, 123/125I-2-iodo-D-phenylalanine was developed, and its tumor-detecting characteristics were evaluated in vivo.123I labeling of 2-iodo-D-phenylalanine was performed with a kit formulation by use of Cu1+-assisted nucleophilic exchange. 123I-2-Iodo-D-phenylalanine was evaluated in R1M tumor-bearing athymic mice by dynamic planar imaging (DPI) and dissection. The in vivo stability of the tracer was tested by high-performance liquid chromatography. Tumor tracer retention and tracer contrast were evaluated as a function of time. Two-compartment blood modeling from DPI results and dosimetric calculations from biodistribution results were carried out. Moreover, 125I-2-iodo-D-phenylalanine and 18F-FDG uptake in acute inflammation was investigated.123I-2-Iodo-D-phenylalanine was metabolically stable. Fast, high, and specific tumor retention was observed. Two-compartment modeling confirmed the fast clearance of the tracer through the kidneys to the bladder, as observed by DPI and dissection. Moreover, compared with the L-isomer, 123I-2-iodo-D-phenylalanine demonstrated faster clearance and faster uptake in the peripheral compartment. No accumulation in the abdomen or in the brain was noted. Dosimetry revealed that 123I-2-iodo-D-phenylalanine demonstrated a low radiation burden comparable to those of 123I-2-iodo-L-phenylalanine and 123I-2-iodo-L-tyrosine. Although 123I-2-iodo-D-phenylalanine showed a tumor retention of only 4%, the tumor contrast was increased up to 350% at 19 h after injection.123I-2-Iodo-D-phenylalanine is a promising tracer for diagnostic oncologic imaging because of its high, fast, and specific tumor uptake and fast clearance from blood.

This study aimed to investigate the feasibility of the intraarterial administration of 3.7 GBq (188)Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for treatment of hepatocellular carcinoma (HCC) in patients with moderately advanced cirrhosis.Patients with HCC and underlying cirrhosis classified as Child-Pugh B in terms of severity were eligible. Whole-body scintigraphies were performed at 4 time points after injection. Absorbed doses to the various organs were calculated according to the MIRD formalism. Urine was collected for 52 h after injection. Toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria for Adverse Events (version 3.0) scale. Responses were evaluated on MRI and by alpha-fetoprotein (AFP) monitoring.A mean activity +/- SD of 3.7 +/- 0.2 GBq (188)Re-HDD/lipiodol was administered in the hepatic artery to 12 patients; 36.2% +/- 5.7% of the activity was excreted in the urine 52 h after injection. The absorbed dose to the liver, lungs, kidney, and thyroid was 7.6 +/- 2.9, 4.8 +/- 2.6, 0.8 +/- 0.7, and 0.2 +/- 0.1 Gy (mean +/- SD), respectively. Two weeks after administration, 6 of 12 patients had adverse events consisting of aggravations of preexisting laboratory changes (3 patients), fatigue (2 patients), vomiting (1 patient), fever (1 patient), encephalopathy (1 patient), and ascites (1 patient). Toxicity assessment at week 6 revealed single cases of the worsening of hyperbilirubinemia, pleural effusion, thrombocytopenia, and dyspnea. Three patients dropped out of the study because of deterioration of their general condition. The response was assessable by MRI in 8 patients: 1 patient with a partial response and 7 patients with stable disease were reported. Nine patients with an initially elevated AFP were evaluated. Stable AFP was recorded in 1 patient and 3 showed a reduction, whereas a considerable increase was observed in 5 patients.After the administration of 3.7 GBq (188)Re-HDD/lipiodol, half of the Child-Pugh B patients in the present study had a worsening of their general condition or aggravation of preexisting symptoms. This was associated with a rise in AFP in a considerable number of patients. In the future, administration of the radiopharmaceutical as close to the tumor feeding arteries as possible might avoid further deterioration of the liver function and show enhanced antitumoral activity.

The aim of this study was to investigate the pharmacokinetics, organ dosimetry, and toxicity after the intraarterial administration of (188)Re-labeled 4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for palliative treatment of hepatocellular carcinoma (HCC). A secondary objective was to document the response.A mean activity of 3.60 GBq (188)Re-HDD/lipiodol (range, 1.86-4.14 GBq) was administered to 11 patients (16 treatment sessions) via a transfemoral catheter. The pharmacokinetic and dosimetric data were collected by means of venous blood samples, urine collections, and 4 or 5 gamma-scintigraphies over 76 h. Absorbed doses to the various organs were calculated according to the MIRD formalism, using the MIRDOSE3.1 software. The toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria scale. The response was evaluated on MRI and by monitoring of the tumor marker.A fast blood clearance of the injected activity was observed with a calculated effective half-life of 7.6 +/- 2.2 h (+/-SD) in blood. The predominant elimination of the activity was through urinary excretion with a mean renal clearance of 44.1% +/- 11.7% (+/-SD) of the injected activity within the 76 h after administration. Fecal elimination was negligible. The calculated whole-body effective half-life was 14.3 +/- 0.9 h (+/-SD). The absorbed dose to the liver tissue, the lungs, the kidneys, and the thyroid was 4.5 +/- 1.9, 4.1 +/- 1.2, 0.9 +/- 0.7, and 0.3 +/- 0.1 Gy, respectively. Treatment was well tolerated, except in 2 patients. One Child B patient experienced a worsening of his liver dysfunction (hyperbilirubinemia) and another patient experienced dyspnea and coughing. Response assessment on MRI showed 1 case of partial response, disease stabilization in 11 treatments, and progressive disease in 1 treatment. In 5 of 8 treatment sessions with an initially elevated alpha-fetoprotein, a reduction (range, 19%-90%) was observed 6 wk later.After the intraarterial administration of 3.60 GBq (188)Re-HDD/lipiodol, a fast clearance of the activity appearing in the blood is observed and the predominant elimination is through urinary excretion. The tolerance as well as the preliminary response rates of the present phase I study are encouraging.

Background— Because of the higher radiosensitivity of infants and children compared with adults, there is a need to evaluate the doses delivered to pediatric patients who undergo interventional cardiac procedures. However, knowledge of the effective dose in pediatric interventional cardiology is very limited. Methods and Results— For an accurate risk estimation, a patient-specific Monte Carlo simulation of the effective dose was set up in 60 patients with congenital heart disease who underwent diagnostic (n=28) or therapeutic (n=32) cardiac catheterization procedures. The dose-saving effect of using extra copper filtration in the x-ray beam was also investigated. For diagnostic cardiac catheterizations, a median effective dose of 4.6 mSv was found. Therapeutic procedures resulted in a higher median effective dose of 6.0 mSv because of the prolonged use of fluoroscopy. The overall effect of inserting extra copper filtration into the x-ray beam was a total effective dose reduction of 18% with no detrimental effect on image quality. An excellent correlation between the dose-area product and effective patient dose was found ( r =0.95). Hence, dose-area product is suitable for online estimation of the effective dose with good accuracy. With all procedures included, the resulting median lifetime risk for stochastic effects was 0.08%. Conclusions— Because of the high radiation exposure, it is important to monitor patient dose by dose-area product instrumentation and to use additional beam filtration to keep the effective dose as low as possible in view of the sensitivity of the pediatric patients.

This study reports on the in vitro evaluation, biodistribution, and dosimetry of (123)I-labeled monoclonal antibody (mAb) 14C5, a new antibody-based agent proposed for radioimmunodetection of tumor growth and metastasis in vivo.(123)I-mAb 14C5 was prepared by direct iodination and tested for stability in vitro. Binding assays were performed on human SK-BR-3 and HeLa carcinoma cells to investigate the antigen expression, antibody affinity, and kinetics of tracer binding. For the biodistribution and dosimetry study, 3- to 4-wk-old NMRI mice were injected intravenously with (123)I-mAb 14C5 (148.0 +/- 7.4 kBq per mouse) and killed at preset time intervals. Organs, blood, urine, and feces were counted for radioactivity uptake, and the data were expressed as the percentage injected dose per gram tissue (%ID/g tissue) or %ID. The MIRDOSE3.0 program was applied to extrapolate the estimated absorbed radiation doses for various organs to the human reference adult.(123)I-mAb 14C5 was obtained in radiochemical yields of 85.0% +/- 2.5% and radiochemical purities were97%. The iodinated antibody demonstrated good in vitro stability with 93.6% +/- 0.1% of (123)I-mAb 14C5 remaining intact at 24 h after radiolabeling. (123)I-mAb 14C5 bound to SK-BR-3 cells (dissociation constant [K(d)] approximately 0.85 +/- 0.17 nmol/L) and HeLa cells (K(d) approximately 1.71 +/- 0.17 nmol/L) with nanomolar affinity and high specificity, whereas both cell types exhibited a high CA14C5 antigen expression (maximum number of binding sites [B(max)] = 40.6 +/- 5.2 and 57.1 +/- 9.6 pmol/L, respectively). In mice, (123)I-mAb 14C5 accumulated primarily in lungs (20.4 %ID/g), liver (15.1 %ID/g), and kidneys (11.1 %ID/g) within 5 min after injection. A delayed uptake was observed in stomach (12.8 %ID/g) and urinary bladder (8.7 %ID/g) at 3 and 6 h, respectively, after injection. Radioactivity clearance was predominantly urinary, with 44.9 +/- 4.5 %ID excreted during the initial 48 h after administration (cumulative amount). The highest absorbed radiation doses determined for the human reference adult were received by the urinary bladder wall (0.1200-0.1210 mGy/MBq), liver (0.0137-0.0274 mGy/MBq), uterus (0.0196-0.0207 mGy/MBq), and lower large intestine wall (0.0139-0.0258 mGy/MBq). The average effective dose resulting from a single (123)I-mAb 14C5 injection was estimated to be 0.017-0.022 mSv/MBq.(123)I-mAb 14C5 shows good in vitro biologic activity and favorable biodistribution properties for imaging carcinomas of different origin and provides an acceptable radiation dose to the patient.

One approach to treatment of primary hepatocellular carcinoma (HCC) is intraarterial injection of (131)I-lipiodol. Although clinical results have been positive, the therapy can be improved by using (188)Re instead of (131)I as the radionuclide. (188)Re is a high-energy beta-emitter, has a shorter half-life than (131)I, and has only low-intensity gamma-rays in its decay. The present study compared the cytotoxic effect of the radionuclide therapy in HCC patients treated with (131)I-lipiodol and (188)Re-4-hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)/lipiodol. To this end, dicentric chromosomes (DCs) were scored in metaphase spreads of peripheral blood cultures. The equivalent total-body dose was deduced from the DC yields using an in vitro dose-response curve.Twenty (131)I-lipiodol treatments and 11 (188)Re-HDD/lipiodol treatments were performed on, respectively, 16 and 7 patients with inoperable HCC. Patients received a mean activity of 1.89 GBq of (131)I-lipiodol or 3.56 GBq of (188)Re-HDD/lipiodol into the liver artery by catheterization. For each patient, a blood sample was taken during the week before therapy. A blood sample was also taken 7 and 14 d after administration for the patients treated with (131)I-lipiodol and 1 or 2 d after administration for the patients treated with (188)Re-HDD/lipiodol.The mean DC yield of (188)Re-HDD/lipiodol therapy (0.087 DCs per cell) was significantly lower than that of (131)I-lipiodol therapy (0.144 DCs per cell) for the administered activities. Corresponding equivalent total-body doses were 1.04 Gy for (188)Re-HDD/lipiodol and 1.46 Gy for (131)I-lipiodol. Data analysis showed that, in comparison with (131)I-lipidol, (188)Re-HDD/lipiodol yielded a smaller cytotoxic effect and a lower radiation exposure for an expected higher tumor-killing effect.(188)Re is a valuable alternative for (131)I in the treatment of HCC with radiolabeled lipiodol, and a dose escalation study for (188)Re-HDD/lipiodol therapy is warranted.

Objectives Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. Methods From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. Results Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose–response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. Conclusion CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. Key Points • CT induces a small, significant number of double-strand DNA breaks in children. • More effective CT dose reduction results in less DNA damage. • Risk estimates based on the LNT hypothesis may represent underestimates.