Positron emission tomography (PET) is increasingly used for the detection, characterization, and follow-up of tumors located in the thorax. However, patient respiratory motion presents a unique limitation that hinders the application of high-resolution PET technology for this type of imaging. Efforts to transcend this limitation have been underway for more than a decade, yet PET remains for practical considerations a modality vulnerable to motion-induced image degradation. Respiratory motion control is not employed in routine clinical operations. In this article, we take an opportunity to highlight some of the recent advancements in data-driven motion control strategies and how they may form an underpinning for what we are presenting as a fully automated data-driven motion control framework. This framework represents an alternative direction for future endeavors in motion control and can conceptually connect individual focused studies with a strategy for addressing big picture challenges and goals.Electronic supplementary materialThe online version of this article (doi:10.1186/2197-7364-1-8) contains supplementary material, which is available to authorized users.

Cancer immunotherapy is changing the imaging evaluation of cancer treatment response and treatment-related toxic effects. New emerging patterns of treatment response and treatment-related toxic effects after treatment with immunomodulating agents have been observed. Treatment response after immunomodulatory therapy can be associated with significantly delayed decrease in tumor size, and new or enlarging tumors observed soon after completion of treatment may not reflect disease progression. In addition, activation of the immune system to fight cancer may lead to unwanted autoimmune-mediated toxic effects that could be mistaken for metastatic disease or misdiagnosed as a non-treatment-related process and delay appropriate clinical management. Radiologists must recognize the novel treatment response patterns and the wide range of autoimmune toxic effects, which should not be mistaken for treatment failure or metastatic disease progression.

Purpose To assess the performance of hardware- and software-gating technologies in terms of qualitative and quantitative characteristics of respiratory motion in positron emission tomography (PET) imaging. Materials and Methods Between 2010 and 2013, 219 fluorine 18 fluorodeoxyglucose PET examinations were performed in 116 patients for assessment of pulmonary nodules. All patients provided informed consent in this institutional review board-approved study. Acquisitions were reconstructed as respiratory-gated images by using hardware-derived respiratory triggers and software-derived signal (via an automated postprocessing method). Asymmetry was evaluated in the joint distribution of reader preference, and linear mixed models were used to evaluate differences in outcomes according to gating type. Results In blind reviews of reconstructed gated images, software was selected as superior 16.9% of the time (111 of 657 image sets; 95% confidence interval [CI]: 14.0%, 19.8%), and hardware was selected as superior 6.2% of the time (41 of 657 image sets; 95% CI: 4.4%, 8.1%). Of the image sets, 76.9% (505 of 657; 95% CI: 73.6%, 80.1%) were judged as having indistinguishable motion quality. Quantitative analysis demonstrated that the two gating strategies exhibited similar performance, and the performance of both was significantly different from that of nongated images. The mean increase ± standard deviation in lesion maximum standardized uptake value was 42.2% ± 38.9 between nongated and software-gated images, and lesion full width at half maximum values decreased by 9.9% ± 9.6. Conclusion Compared with vendor-supplied respiratory-gating hardware methods, software gating performed favorably, both qualitatively and quantitatively. Fully automated gating is a feasible approach to motion correction of PET images. (©) RSNA, 2016 Online supplemental material is available for this article.

Pascal Espié and YanLing He are co-first authors who have contributed equally to the work. James S. Rush and Peter Gergely have contributed equally to the work.Clinical Trial Registration Number: NCT02089087.Abbreviations: AEs, adverse events; AUC last , area under the plasma concentration-time curve from time zero to the last quantifiable concentration; BLQ, below limit of quantification;Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases. K E Y W O R D S clinical research/practice, clinical trial, immunosuppressant -fusion proteins and monoclonal antibodies: B cell specific, immunosuppression/immune modulation, translational research/ science S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Espié P, He Y, Koo P, et al. First-inhuman clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody. Am J Transplant. 2020;20: 463-473. https ://doi.

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Purpose 4DCT-ventilation is an exciting imaging modality that uses 4DCT data to calculate lung function maps. The development of clinical trials is underway to use 4DCT-ventilation imaging to preferentially spare functional lung in patients undergoing radiotherapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer disease Methods and Materials A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient’s 4DCT imaging, deformable image registration, and a density-change based algorithm. In order to assess each patient’s spatial ventilation profile both quantitative and qualitative metrics were developed including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate weighted mean lung doses (fMLD) and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (p<0.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average fMLD was 19.6 Gy and 5.4 Gy for stage III and I patients respectively with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion Our 118 patient retrospective study found that 65% stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung highlighting the importance of evaluating the function of each patient and developing a personalized functional avoidance treatment approach.

The RADAR III Group recommends NGI techniques for select patients suspected of disease progression based on laboratory (biomarker) values, comorbidities, and symptoms. Currently, F-fluciclovine andGallium (Ga) PSMA PET/CT are the NGI agents with a favorable combination of availability, specificity, and sensitivity. There is ongoing research for additional NGI technologies, which may offer improved diagnostic accuracy and therapeutic options. As NGI techniques evolve and presumably result in improved global accessibility, a clinician's ability to detect micrometastases may be enhanced for both decision-making and patient outcomes.

(177)Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.