The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18 F-fluoride plasma clearance (K i ) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 mg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K i values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K i values increased by 24% (p ¼ .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k 3 /[k 2 þ k 3 ]), which increased by 23% (p ¼ .0006). In contrast to K i , spine SUVs increased by only 3% (p ¼ .84). The discrepancy between changes in K i and SUVs was explained by a 20% decrease in 18 F À plasma concentration. SUVs increased by 37% at the femoral shaft (p ¼ .0019), 20% at the total hip (p ¼ .032), and 11% at the pelvis (p ¼ .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18 F À PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. ß

Patients treated with radioiodine present a radiation hazard and precautions are necessary to limit the radiation dose to family members, nursing staff and members of the public. The precautions advised are usually based on instantaneous dose rates or iodine retention and do not take into account the time spent in close proximity with a patient. We have combined whole-body dose rate measurements taken from 86 thyroid cancer patients after radioiodine administration with published data on nursing and social contact times to calculate the cumulative dose that may be received by an individual in contact with a patient. These dose estimates have been used to calculate restrictions to patients behaviour to limit received doses to less than 1 mSv. We have also measured urinary iodide excretion in 19 patients to estimate the potential risk from the discharge of radioiodide into the domestic drainage system. The dose rate decay was biexponential for patients receiving radioiodine to ablate the thyroid after surgery (the ablation group, A) and monoexponential for these receiving subsequent treatments for residual or recurrent disease (the follow-up group, FU). The faster clearance in the follow-up patients generally resulted in less stringent restrictions than those advised for ablation patients. For typical activities of 1850 MBq for the ablation patients and 3700 MBq or 7400 MBq for the follow-up patients, the following restrictions were advised. Patients could travel in a private car for up to 8h on the day of treatment (for an administered activity of 1850 MBq in group A) or 4 and 2h (for activities of 3700 or 7400 MBq in group FU) respectively. Patients should remain off work for 3 days (1850 MBq/group A) or 2 days (up to 7400 MBq/group FU). Partners should avoid close contact and sleep apart for 16 days (1850 MBq/group A) or 4-5 days (3700 or 7400 MBq/group FU). Contact with children should be restricted according to their age, ranging from 16 days (1850 MBq/group A) or 4-5 days (3700 or 7400 MBq in group FU) for younger children, down to 10 days (1850 MBq/group A) or 4 days (up to 7400 MBq/group FU) for older children. The cumulative dose to nursing staff for the week after treatment was dependent on patient mobility and was estimated at 0.08 mSv for a self-caring patient to 6.3 mSv for a totally helpless patient (1840 MBq/group A). Corresponding doses to nurses looking after patients in group FU were 0.18-12.3 mSv (3700 MBq) or 0.36-24.6 mSv (7400 MBq). Sensible guidelines can be derived to limit the dose received by members of the public and staff who may come into contact with cancer patient treated with radioiodine to less than 1 mSv. The rapid clearance of radioiodine in patients treated on one or more than one occasion means that therapy could be administered at home to selected patients with suitable domestic circumstances. In most cases the restriction times, despite the high administered activities, are less than those for patients treated for thyrotoxicosis. The concentration of radioiodide in domestic dr...

We have investigated improvements to PET-MR image registration offered by PET-CT scanning. Ten subjects with suspected soft-tissue sarcomas were scanned with an in-line PET-CT and a clinical MR scanner. PET to CT, CT to MR and PET to MR image registrations were performed using a rigid-body external marker technique and rigid and non-rigid voxel-similarity algorithms. PET-MR registration was also performed using transformations derived from the registration of CT to MR. The external marker technique gave fiducial registration errors of 2.1 mm, 5.1 mm and 5.3 mm for PET-CT, PET-MR and CT-MR registration. Target registration errors were 3.9 mm, 9.0 mm and 9.3 mm, respectively. Voxel-based algorithms were evaluated by measuring the distance between corresponding fiducials after registration. Registration errors of 6.4 mm, 14.5 mm and 9.5 mm, respectively, for PET-CT, PET-MR and CT-MR were observed for rigid-body registration while non-rigid registration gave errors of 6.8 mm, 16.3 mm and 7.6 mm for the same modality combinations. The application of rigid and non-rigid CT to MR transformations to accompanying PET data gives significantly reduced PET-MR errors of 10.0 mm and 8.5 mm, respectively. Visual comparison by two independent observers confirmed the improvement over direct PET-MR registration. We conclude that PET-MR registration can be more accurately and reliably achieved using the hybrid technique described than through direct rigid-body registration of PET to MR.

The fusion of functional positron emission tomography (PET) data with anatomical magnetic resonance (MR) or computed tomography images, using a variety of interactive and automated techniques, is becoming commonplace, with the technique of choice dependent on the specific application. The case of PET-MR image fusion in soft tissue is complicated by a lack of conspicuous anatomical features and deviation from the rigid-body model. Here we compare a point-based external marker technique with an automated mutual information algorithm and discuss the practicality, reliability and accuracy of each when applied to the study of soft tissue sarcoma. Ten subjects with suspected sarcoma in the knee, thigh, groin, flank or back underwent MR and PET scanning after the attachment of nine external fiducial markers. In the assessment of the point-based technique, three error measures were considered: fiducial localisation error (FLE), fiducial registration error (FRE) and target registration error (TRE). FLE, which represents the accuracy with which the fiducial points can be located, is related to the FRE minimised by the registration algorithm. The registration accuracy is best characterised by the TRE, which is the distance between corresponding points in each image space after registration. In the absence of salient features within the target volume, the TRE can be measured at fiducials excluded from the registration process. To assess the mutual information technique, PET data, acquired after physically removing the markers, were reconstructed in a variety of ways and registered with MR. Having applied the transform suggested by the algorithm to the PET scan acquired before the markers were removed, the residual distance between PET and MR marker-pairs could be measured. The manual point-based technique yielded the best results (RMS TRE =8.3 mm, max =22.4 mm, min =1.7 mm), performing better than the automated algorithm (RMS TRE =20.0 mm, max =30.5 mm, min =7.7 mm) when registering filtered back-projection PET images to MR. Image reconstruction with an iterative algorithm or registration of a composite emission-transmission image did not improve the overall accuracy of the registration process. We have demonstrated that, in this application, point-based PET-MR registration using external markers is practical, reliable and accurate to within approximately 5 mm towards the fiducial centroid. The automated algorithm did not perform as reliably or as accurately.

With the increasing use of positron emission tomography (PET) for disease staging, follow-up and therapy monitoring in a number of oncological indications there is growing interest in the use of PET and PET-CT for radiation treatment planning. In order to create a strong clinical evidence base for this, it is important to ensure that research data are clinically relevant and of a high quality. Therefore the National Cancer Research Institute PET Research Network make these recommendations to assist investigators in the development of radiotherapy clinical trials involving the use of PET and PET-CT. These recommendations provide an overview of the current literature in this rapidly evolving field, including standards for PET in clinical trials, disease staging, volume delineation, intensity modulated radiotherapy and PET-augmented planning techniques, and are targeted at a general audience. We conclude with specific recommendations for the use of PET in radiotherapy planning in research projects.

New positron emission tomography (PET) tracers could have a substantial impact on early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) progression, particularly if they are accompanied by optimised deep learning methods. To realize the full potential of deep learning for PET imaging, large datasets are required for training. However, dataset sizes are restricted due to limited availability. Meanwhile, most of the AD classification studies have been based on structural MRI rather than PET. In this paper, we propose a novel application of conditional Generative Adversarial Networks (cGANs) to the generation of 𝐹 18 -florbetapir PET images from corresponding MRI images. Furthermore, we show that generated PET images can be used for synthetic data augmentation, and improve the performance of 3D Convolutional Neural Networks (CNN) for predicting progression to AD. Our method is applied to a dataset of 79 PET images, obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We generate high quality PET images from corresponding MRIs using cGANs, and we evaluate the quality of generated PET images by comparison to real images. We then use the trained cGANs to generate synthetic PET images from additional MRI dataset. Finally we build a 152-layer ResNet to compare the MCI classification performance using both traditional data augmentation method and our proposed synthetic data augmentation method. Mean Structural Similarity (SSIM) index was 0.95± 0.05 for generated PET and real PET. For MCI progression classification, the traditional data augmentation method showed 75% accuracy while the synthetic data augmentation improved this to 82%.

Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for α v β 3 /α v β 5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, 18 F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of 18 F-fluciclatide in multiple solid-tumor types. Methods: Thirtynine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of 18 F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. 18 F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Results: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r 5 0.92, P , 0.05, at 40 min; r 5 0.94, P , 0.05, at 65 min; r 5 0.94, P , 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter 18 F-FDG studies. Conclusion: The test-retest reproducibility of 18 F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.