Performing [18F]MFBG Long-Axial-Field-of-View PET/CT Without Sedation or General Anesthesia for Imaging of Children with Neuroblastoma.

Meta-[123I]iodobenzylguanidine ([123I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [123I]MIBG with the new PET tracer meta-[18F]fluorobenzylguanidine ([18F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [18F]MFBG LAFOV PET/CT and compare it with [123I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [123I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [123I]MIBG scintigraphy and SPECT/low-dose CT, [18F]MFBG LAFOV PET/ultra-low-dose CT was performed 1 h after injection (1.5-3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [123I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [18F]MFBG was produced in a fully automated good manufacturing practice-compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [18F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1-7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [123I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [18F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [18F]MFBG LAFOV PET/CT compared with [123I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [18F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma.

The effect of 99mTc on dual-energy X-ray absorptiometry measurement of body composition and bone mineral density.

Whether the γ-emission by radioisotopes influences the outcome of dual-energy X-ray absorptiometry (DXA) measurements is not fully elucidated. The aim of this study was to evaluate the effect of antecedent administration of 99mTc on DXA measurements regarding body composition and bone mineral density (BMD) using a K-edge filter scanner. The phantom measurements were performed by placing a urinary bladder phantom containing 40 mL of radioisotope solution on the pelvic region of a whole-body phantom. Twenty-seven patients attending our department for a routine examination involving the administration of a tracer marked with 99mTc were included. The patients underwent a whole-body DXA scan before and within 2 h after tracer injection using a GE/Lunar Prodigy scanner. Control scans were performed on 40 volunteers, who had not received any radioactive tracer. In both phantom and patient measurements, we found a significant dose-related decrease in fat mass and BMD and a corresponding increase in fat-free mass (p < 0.001). Based on the linear regression analysis, we suggest upper dose limits for the measurement of BMD at 0.77 µSv/h and body composition at 0.21 µSv/h (dose rate measured at a distance of 1m from the patient). Caution should be taken when interpreting the results of DXA scans performed in close temporal proximity to procedures involving the administration of 99mTc.

Imaging modalities for pulmonary tuberculosis in children: A systematic review.

Purpose: The optimal choice of protocol for diagnostic imaging in children with tuberculosis (TB) is a contemporary challenge due to the war in Ukraine, which potentially can create a steep rise in TB cases in Western Europe. We aimed to gather all primary research comparing imaging modalities and their diagnostic accuracies for pulmonary findings in children with suspected or confirmed pulmonary tuberculosis (PTB). Method: We searched the databases PubMed and Embase using pre-specified search terms, for English- and non-English published and un-published reports from the period 1972 to 2022. We retrieved reports via citation search in excluded literature reviews and systematic reviews. Studies were eligible if most of the study population was between 0 and 18 years of age with confirmed or suspected PTB, and study participants had described diagnostic images from two or more different imaging modalities. Results: A total of 15 studies investigated conventional chest X-Ray (CXR) and computed tomography (CT) in diagnosing PTB in children. Nine studies investigated the number of participants in where CT or CXR confirmed the diagnosis of TB, and all of them, including a total of 1244 patients, reported that findings compatible with TB were more frequently detected on CT than CXR. Only two studies did not include radiological findings as part of their diagnostic criteria for PTB, and combined they showed that CT diagnosed 54/54 (100 %) children with confirmed PTB, while CXR diagnosed 42/54 (78 %). Two studies compared magnetic resonance imaging (MRI) with CXR and showed that MRI diagnosed more children with PTB than CXR. One study reported a higher positive predictive value (PPV), sensitivity and specificity for PTB findings for MRI than CXR. One study compared CXR with high-kilovolt (high-kV) CXR, finding compatible sensitivity and specificity regarding confirmation of PTB. Two studies compared ultrasound (US) with CXR and found that US had a higher diagnostic yield and more often correctly identified consolidations, mediastinal LAP, and pleural effusion. Conclusion: CT showed a higher diagnostic accuracy for PTB findings than CXR, MRI and US, and should be the imaging modality of first choice when available. MRI had a higher sensitivity and specificity than CXR for LAP, pleural effusion, and cavitation. US was complimentary in initial diagnostic work-up and follow up. A diagnostic strategy for PTB in children according to local availability and expertise is proposed, as no evidence from this systematic review shows otherwise, in acknowledgement of the expertise in high TB-burdened countries. CT can be performed when in doubt, due to the higher diagnostic yield.

Urokinase-type plasminogen activator receptor (uPAR) assessed by liquid biopsies and PET/CT for prognostication in head and neck cancer patients.

Strong prognostic biomarkers are lacking regarding the stratification of treatment and surveillance regimens in head and neck squamous cell carcinoma (HNSCC). The study aimed to assess the prognostic value of soluble urokinase-type plasminogen activator receptor in plasma (suPAR) compared to evaluation by uPAR-positron-emission-tomography (PET) in HNSCC patients. Plasma from 19 controls and 49 HNSCC patients referred to curatively intended radiotherapy (2017-2021) was collected pre-treatment and post-treatment (n = 37). Information on uPAR-PET was available from previous evaluation. Patient median suPAR was significantly higher pre- and post-treatment compared to controls (p = 0.013, p = 0.003) and increased significantly during radiotherapy (p = 0.003). Pre-treatment suPAR did not predict survival outcomes. Post-treatment suPAR significantly predicted RFS (HR = 6.67 (95% CI 1.44-30.9) p = 0.015), but not OS (HR = 3.29 (95% CI 0.882-12.3) p = 0.076) in univariate analysis. RFS prediction was maintained for post-treatment suPAR in multivariate analysis, including TNM-stage (HR = 6.62 (95% CI 1.40-31.4) p = 0.017). Pre-treatment uPAR-PET/CT and post-treatment suPAR was available in 24 patients. High uPAR-estimates on both modalities was significantly associated with poor RFS compared to patients with low uPAR-estimates (log-rank, p = 0.008). Patients with discordant uPAR-estimates (one-low/one-high) were at intermediate risk, although non-significant (p = 0.131). In conclusion, pre-treatment suPAR did not predict RFS or OS. Pre-treatment uPAR-PET and post-treatment suPAR predicted RFS.

uPAR PET/CT for Prognostication and Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing Radium-223 Therapy: A Prospective Phase II Study.

The aim of this Phase II study was to investigate the potential for response assessment and prognostication of positron emission tomography (PET) using the ligand 68Ga-NOTA-AE105 targeting the urokinase-type plasminogen activator receptor (uPAR) in patients receiving Radium-223-dichloride therapy (223RaCl2). A combined whole-body uPAR PET and computed tomography (CT) was performed before initiation of 223RaCl2 and after two cycles of therapy. Standardized uptake value (SUV) in selected bone metastases was measured and the lesion with the highest SUVmax was considered the index lesion. Clinical outcomes were overall survival (OS), radiographic progression free survival (rPFS) and occurrence of symptomatic skeletal event (SSE). A total of 17 patients were included and 14 patients completed both baseline and follow-up uPAR-PET/CT. Baseline SUVmax of the index lesion was associated with OS; hazard ratio 2.51 (95% CI: 1.01-6.28, p = 0.05) per unit increase in SUVmax. No association between changes in SUVmax from baseline to follow-up and OS, progression during therapy, or rPFS was found. Baseline SUVmax was a significant predictor of SSE with receiver operating characteristics (ROC) area under the curve (AUC) = 0.81 (95% CI: 0.58-1.00, p = 0.034). A cut-off for tumor SUVmax could be established with an odds ratio of 14.0 (95% CI: 1.14-172.6, p = 0.023) for occurrence of SSE within 12 months. Although based on a small number of patients, uPAR-PET SUVmax in bone metastases was predictive for OS and risk of SSE in mCRPC patients receiving 223RaCl2. However, a relatively low uptake of the uPAR ligand in bone metastases impedes visual evaluation and requires another modality for lesion delineation.

Eosinophilic Cystitis Presenting as Possible Pediatric Rhabdomyosarcoma in Conventional Imaging Including 18F-FDG-PET/CT/MRI-A Rare Case.

Eosinophilic cystitis (EC) is a relatively rare, but benign inflammatory bladder disease compared to that of the malignant pediatric rhabdomyosarcoma (RMS), in which it can be mimicking on initial suspicion. The origin, symptoms and findings of both EC and RMS are still discussed and hence, lead to the challenge in distinguishing them by cystoscopy and several image modalities. We present a case in which cross-sectional imaging modalities including fluorine-18-fluro-2-deoxy-D-glucose (18F-FDG)-positron emission tomography (PET) / computed tomography (CT) / magnetic resonance imaging (MRI) (18F-FDG-PET/CT/MRI (The imaging modality 18F-FDG-PET/CT/MRI referring to two continuous scans scanned on the same 18F-FDG-tracer dose for both the whole-body 18F-FDG-PET/CT and the regional 18F-FDG-PET/MRI of the pelvis.)) raised suspicion of RMS. Hence, the final diagnosis of EC was established by repeated histopathology. It is important to have EC in mind when seeking differential diagnosis of malignant diseases like RMS in order to provide the correct treatment for the patient and highly homogenously increased 18F-FDG-uptake should raise the suspicion of EC as a differential diagnosis. Furthermore, 18F-FDG-uptake rate is suggested as a future potential biomarker for monitoring of therapeutic response in eosinophilic inflammatory diseases, thus more research on this topic is needed.

Urokinase-Type Plasminogen Activator Receptor (uPAR) PET/MRI of Prostate Cancer for Noninvasive Evaluation of Aggressiveness: Comparison with Gleason Score in a Prospective Phase 2 Clinical Trial.

The aim of this study was to evaluate the correlation between uptake of the PET ligand 68Ga-NOTA-AE105, targeting the urokinase-type plasminogen activator receptor (uPAR), and Gleason score in patients undergoing prostate biopsy. Methods: Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase 2 trial. A combination of uPAR PET and multiparametric MRI (mpMRI) was performed, and the SUV in the primary tumor, as delineated by mpMRI, was measured by 2 independent readers. The correlation between the SUV and the Gleason score obtained by biopsy was assessed. Results: A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between the SUVmax and the Gleason score (Spearman ρ = 0.55; P = 0.003). Receiver operating characteristic analysis showed an area under the curve of 0.88 (95% CI, 0.67-1.00) for discriminating a Gleason score of greater than or equal to 3 + 4 from a Gleason score of less than or equal to 3 + 3. A cutoff for the tumor SUVmax could be established with a sensitivity of 96% (79%-99%) and a specificity of 75% (30%-95%) for detecting a Gleason score of greater than or equal to 3 + 4. For discriminating a Gleason score of greater than or equal to 4 + 3 from a Gleason score of less than or equal to 3 + 4, a cutoff could be established for detecting a Gleason score of greater than or equal to 4 + 3 with a sensitivity of 93% (69%-99%) and a specificity of 62% (36%-82%). Conclusion: SUV measurements from uPAR PET in primary tumors, as delineated by mpMRI, showed a significant correlation with the Gleason score, and the tumor SUVmax was able to discriminate between low-risk Gleason score profiles and intermediate risk Gleason score profiles with a high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for the noninvasive evaluation of PCa and might reduce the need for repeated biopsies (e.g., in active surveillance).

Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study.

BACKGROUND: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. METHODS: A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV1) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation. RESULTS: In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group. CONCLUSIONS: Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post hoc exploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.

223Ra Therapy of Advanced Metastatic Castration-Resistant Prostate Cancer: Quantitative Assessment of Skeletal Tumor Burden for Prognostication of Clinical Outcome and Hematologic Toxicity.

The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving 223RaCl2 We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with 223RaCl2Methods: This study was a retrospective investigation of a Danish cohort of mCRPC patients who received 223RaCl2 therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI BoneBSI) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. Results: A total of 88 patients were included. The median number of completed 223RaCl2 cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; P = 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; P = 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of 223RaCl2 (n = 52) and in 84% of the patients after the end of therapy (n = 32). There was no significant association between a change in the BSI during therapy and OS. Conclusion: The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receiving 223RaCl2 Further prospective studies are needed to evaluate the potential of the BSI for response assessment in 223RaCl2 therapy.

An Uncommon Case of Pediatric Esthesioneuroblastoma Presenting as SIADH: 18F-FDG PET/CT in Staging and Post-Therapeutic Assessment.

Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from the olfactory neuroepithelium and accounts for 3-6% of all intranasal tumors [¹]. ENBs can be locally aggressive and cause invasion and destruction of surrounding structures. Histological grading and clinical stage at presentation are highly predictive of survival and especially presence of lymph node and distant metastases are determining prognostic factors [²,³,4,5]. Thus, reliable imaging is essential in these patients. Conventional imaging modalities for staging ENB are magnetic resonance imaging (MRI) and computed tomography (CT). However, fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (18F-FDG PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of ENB patients compared to conventional imaging [6]. We present a case demonstrating the diagnostic work-up and follow-up with 18F-FDG PET/CT in a young patient with ENB with a highly atypical clinical presentation.

Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients.

BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy. MATERIALS AND METHODS: Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015. End points were number of completed Ra-223 cycles, overall survival (OS) and radiographic progression-free survival (rPFS). Bone scintigraphy, CT of thorax and abdomen, hematological status, PSA and alkaline phosphatase were evaluated prior to first dose and after 3rd and 6th treatment, respectively. Follow-up period was 18 months after first Ra-223 cycle. RESULTS: A total of 50 consecutive patients initiated Ra-223 therapy in the time period. Seventeen of 50 patients (34%) had prolonged interval between cycles due to delivery problems. Median delay was 4 weeks (range 3-9 weeks). Patients with delayed treatment had significantly longer median rPFS [delayed patients: 7.1 months (95% CI 4.9-9.3) vs. 4.5 months (95% CI 2.8-6.3)]. There was no significant difference in number of completed cycles or median OS. CONCLUSION: We find no negative impact of prolonged interval between Ra-223 cycles due to non-disease related reasons on OS, rPFS or number of completed treatment cycles.

Contemporary methods of body composition measurement.

Reliable and valid body composition assessment is important in both clinical and research settings. A multitude of methods and techniques for body composition measurement exist, all with inherent problems, whether in measurement methodology or in the assumptions upon which they are based. This review is focused on currently applied methods for in vivo measurement of body composition, including densitometry, bioimpedance analysis, dual-energy X-ray absorptiometry, computed tomography (CT), magnetic resonance techniques and anthropometry. Multicompartment models including quantification of trace elements by in vivo neutron activation analysis, which are regarded as gold standard methods, are also summarized. The choice of a specific method or combination of methods for a particular study depends on various considerations including accuracy, precision, subject acceptability, convenience, cost and radiation exposure. The relative advantages and disadvantages of each method are discussed with these considerations in mind.

Rate and predictors of the conversion of abstracts presented at the Canadian Cardiovascular Congress scientific meetings to full peer-reviewed publications.

The rate of conversion of abstracts presented at scientific meetings into peer-reviewed published manuscripts is an important metric for medical societies, because it facilitates translation of scientific knowledge into practice. We determined the rate and predictors of conversion of scientific abstracts presented at the Canadian Cardiovascular Congress (CCC) from 2006 to 2010 into peer-reviewed article publications within 2 years of their initial presentation. Using a previously validated computer algorithm, we searched the International Statistical Institute Web of Science to identify peer-reviewed full manuscript publications of these abstracts. A multivariable logistic regression was used to identify independent factors associated with successful publication. From 2006 to 2010, 3565 abstracts were presented at the CCC. Overall 24.1% of presented abstracts were published within 2 years of the conference. Mean impact factor for publications was 5.2 (range, 0.4-53.2). The type of presentation (for poster vs oral; odds ratio, 0.71; 95% confidence interval, 0.60-0.83; P < 0.001) and category of presentation (P < 0.001) were significantly associated with successful publication. Late breaking abstracts and those related to cancer and clinical sciences were more likely to be published, compared with prevention, vascular biology, and pediatrics. In conclusion, the publication rate at the CCC is only marginally lower than that reported for large international North American and European cardiology conferences (30.6%). Efforts should focus on several identified barriers to improve conversion of abstracts to full report publication.