Biodistribution and radiation dosimetry of the 18?kDa translocator protein (TSPO) radioligand [18F]FEDAA1106: a human whole-body PET study

Purpose

[¹⁸F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18?kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [¹⁸F]FEDAA1106 based on human whole-body PET measurements.

Methods

PET scans were performed for a total of 6.6?h after the injection of 183.8?±?9.1?MBq of [¹⁸F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software.

Results

Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2?h), liver (21.1%ID at 0.6?h), small intestine (10.4%ID at 6.3?h), kidney (4.9%ID at 1.8?h) and spleen (4.6%ID at 0.6?h). The largest absorbed dose was found in the spleen (0.12?mSv/MBq), followed by kidneys (0.094?mSv/MBq). The calculated mean effective dose was 0.036?mSv/MBq.

Conclusion

Based on the distribution and dose estimates, the estimated radiation burden of [¹⁸F]FEDAA1106 is moderately higher than that of [¹⁸F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies.     

Value of a Dixon-based MR/PET attenuation correction sequence for the localization and evaluation of PET-positive lesions

Purpose

In this study, the potential contribution of Dixon-based MR imaging with a rapid low-resolution breath-hold sequence, which is a technique used for MR-based attenuation correction (AC) for MR/positron emission tomography (PET), was evaluated for anatomical correlation of PET-positive lesions on a 3T clinical scanner compared to low-dose CT. This technique is also used in a recently installed fully integrated whole-body MR/PET system.

Methods

Thirty-five patients routinely scheduled for oncological staging underwent ¹⁸F-fluorodeoxyglucose (FDG) PET/CT and a 2-point Dixon 3-D volumetric interpolated breath-hold examination (VIBE) T1-weighted MR sequence on the same day. Two PET data sets reconstructed using attenuation maps from low-dose CT (PET_{AC_CT}) or simulated MR-based segmentation (PET_{AC_MR}) were evaluated for focal PET-positive lesions. The certainty for the correlation with anatomical structures was judged in the low-dose CT and Dixon-based MRI on a 4-point scale (0?C3). In addition, the standardized uptake values (SUVs) for PET_{AC_CT} and PET_{AC_MR} were compared.

Results

Statistically, no significant difference could be found concerning anatomical localization for all 81 PET-positive lesions in low-dose CT compared to Dixon-based MR (mean 2.51?±?0.85 and 2.37?±?0.87, respectively; p?=?0.1909). CT tended to be superior for small lymph nodes, bone metastases and pulmonary nodules, while Dixon-based MR proved advantageous for soft tissue pathologies like head/neck tumours and liver metastases. For the PET_{AC_CT}- and PET_{AC_MR}-based SUVs (mean 6.36?±?4.47 and 6.31?±?4.52, respectively) a nearly complete concordance with a highly significant correlation was found (r?=?0.9975, p?Conclusion Dixon-based MR imaging for MR AC allows for anatomical allocation of PET-positive lesions similar to low-dose CT in conventional PET/CT. Thus, this approach appears to be useful for future MR/PET for body regions not fully covered by diagnostic MRI due to potential time constraints.     

Which patients with type 2 diabetes mellitus are perceived as ‘difficult’ by general practitioners?

AimsTo find factors that are associated with a general practitioner’s (GP’s) subjective impression of a patient being ‘difficult’ within a sample of patients with type 2 diabetes mellitus (T2DM).MethodsSecondary cross-sectional analysis of a cohort of GP patients with T2DM. GP questionnaire on clinical data and GPs’ subjective ratings of patient attributes (including ‘patient difficulty’). Patient questionnaire on sociodemographics and illness perceptions. Bivariate and multivariate analyses, adjusted for cluster-effect of GP practice.ResultsData from 314 patients from 49 GPs could be analysed. Independent associations with higher GP-rated difficulty were found for (odds ratio; 95% confidence interval): male patients from male GPs (1.27; 1.06–1.53), unmarried men (1.25; 1.04–1.51), men with non-German nationality (1.80; 1.24–2.61), patients perceiving more problems with diabetes (1.17; 1.04–1.30), patients with higher BMI (1.01; 1.00–1.02) and HbA1c values (1.06; 1.02–1.10), patients being perceived by the GP as less adherent (1.34; 1.22–1.46) and less health-literate (1.19; 1.04–1.35).ConclusionsThe impact of patients’ gender and illness perception yield new insights into GP-perceived complexity of care. Culturally and gender-sensitive communication techniques for adapting health care goals to patients’ problems (rather than norm values) may alleviate GPs’ work.     

Optimism bias leads to inconclusive results-an empirical study

Objective

Optimism bias refers to unwarranted belief in the efficacy of new therapies. We assessed the impact of optimism bias on a proportion of trials that did not answer their research question successfully and explored whether poor accrual or optimism bias is responsible for inconclusive results.

Study Design

Systematic review.

Setting

Retrospective analysis of a consecutive-series phase III randomized controlled trials (RCTs) performed under the aegis of National Cancer Institute Cooperative groups.

Results

Three hundred fifty-nine trials (374 comparisons) enrolling 150,232 patients were analyzed. Seventy percent (262 of 374) of the trials generated conclusive results according to the statistical criteria. Investigators made definitive statements related to the treatment preference in 73% (273 of 374) of studies. Investigators’ judgments and statistical inferences were concordant in 75% (279 of 374) of trials. Investigators consistently overestimated their expected treatment effects but to a significantly larger extent for inconclusive trials. The median ratio of expected and observed hazard ratio or odds ratio was 1.34 (range: 0.19-15.40) in conclusive trials compared with 1.86 (range: 1.09-12.00) in inconclusive studies (P < 0.0001). Only 17% of the trials had treatment effects that matched original researchers’ expectations.

Conclusion

Formal statistical inference is sufficient to answer the research question in 75% of RCTs. The answers to the other 25% depend mostly on subjective judgments, which at times are in conflict with statistical inference. Optimism bias significantly contributes to inconclusive results.     

Targeted Therapeutic Approaches in Vulvar Squamous Cell Cancer (VSCC): Case Series and Review of the Literature

Therapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013–2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: “vulvar cancer” AND “targeted therapy,” “erlotinib,” “EGFR,” “bevacizumab,” “VEGF,” “pembrolizumab,” or “immunotherapy.” Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients [median 3.5 previous lines (range 2–5)]. In the erlotinib subgroup, two of five patients (40%) achieved stable disease (SD), while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in second/third line for a median of 3.4 months (range 2–6 months). Bevacizumab (n = 9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9); best response was complete response (CR) (n = 2/9 22.2%). Median duration of treatment was 7 months (range 4–13 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n = 3) subset was SD (n = 1/3 33%). Treatment was given as monotherapy in second/third line for a median of 3.3 months (range 3–4 months). Nine of 12 patients (75%) experienced treatment-related adverse events (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities; however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.Key words: Vulvar cancer (VC), Targeted therapy, EGFR targeting, VEGF signaling pathway, Immuno-oncology     

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

Background

Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS).

Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients

Purpose

Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.