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OBJECTIVE: Interleukin-15 (IL-15) is a proinflammatory, innate response cytokine that mediates pleiotropic effector function in rheumatoid arthritis (RA) inflammatory synovitis. Our objective was to study the ability of HuMax-IL15, a human IgG1 anti-IL-15 monoclonal antibody, to neutralize exogenous and endogenous IL-15 activity in vitro and to perform a phase I-II dose-escalation trial with HuMax-IL15 in patients with active RA. METHODS: Mononuclear cells from blood and synovial fluid (SF) of RA patients were isolated and cultured in vitro under experimental conditions involving the addition of HuMax-IL15. HuMax-IL15 was administered to 30 RA patients who received no other disease-modifying antirheumatic drugs in a 12-week, dose-ascending, placebo-controlled, double-blind, phase I-II proof-of-concept study. RESULTS: In vitro studies showed that HuMax-IL15 suppressed proliferation and induced apoptosis in an IL-15-dependent cell line, BDB2, and was capable of suppressing the release of interferon-gamma by synovial fluid mononuclear cell (SFMC) cultures induced by exogenous IL-15. Furthermore, HuMax-IL15 F(ab')2 fragments suppressed exogenous IL-15-induced CD69 expression in RA peripheral blood mononuclear cells and SFMCs, which indicates that HuMax-IL15 can specifically neutralize several biologic effects of IL-15 in synovial tissue in vitro. In a phase I-II clinical trial, HuMax-IL15 was well tolerated clinically, with no significant effects on T lymphocyte subset and natural killer cell numbers. Substantial improvements in disease activity were observed according to the American College of Rheumatology criteria for 20% improvement (63% of patients), 50% improvement (38%), and 70% improvement (25%). CONCLUSION: These clinical data suggest for the first time that IL-15 could represent a novel therapeutic target in RA. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea. [ABSTRACT FROM PUBLISHER]

Background: Patients with schizophrenia have an increased prevalence of risk factors for peripheral artery disease (PAD) and is expected to have an increased prevalence of PAD. PAD can be detected utilizing toe-brachial index (TBI) which screens for vascular pathology proximal to the toes., Methods: Using a cross-sectional design, we defined the subpopulations: (1) Patients diagnosed with schizophrenia less than 2 years before inclusion (SCZ < 2), (2) Psychiatric healthy controls matched to subpopulation 1 on sex, age, and smoking status, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (SCZ ≥ 10). TBI was calculated by dividing toe pressures by systolic brachial blood pressure, and PAD was defined by TBI < 0.70. Logistic regression analysis with PAD as outcome and sex, age, smoking status, BMI, skin temperature, diagnosis of schizophrenia, and comorbidities as explanatory variables was conducted., Results: PAD was present in 26.2% of patients diagnosed with SCZ < 2 (17 of 65) and in 18.5% of psychiatric healthy controls (12 of 65) with no statistically significant difference in prevalence rates (p = 0.29). PAD was present in 22.0% of patients diagnosed with SCZ ≥ 10 (31 of 141). In logistic regression, patients diagnosed with SCZ < 2 had an increased odds of PAD with psychiatric healthy controls as reference (Odds ratio = 2.80, 95% confidence interval 1.09-7.23, p = 0.03). The analysis was adjusted for age, sex, smoking status, BMI and comorbidities such as hypertension, diabetes and heart disease., Conclusions: This study did not find statistically significant increased prevalence rates of PAD in patients with schizophrenia even though patients with SCZ were compared to psychiatric healthy controls using TBI. Utilizing logistic regression PAD was associated with schizophrenia diagnosis within the last 2 years, age and skin temperature. As PAD is initially asymptomatic, screening could be relevant in patients with schizophrenia if other risk factors are prevalent. Further large-scale multicenter studies are warranted to investigate schizophrenia as a potential risk factor for PAD., Trial Registration: Clinicaltrials.gov identifier NCT02885792., (© 2023. The Author(s).)

Aim: To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging., Methods: At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up., Results: Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%)., Conclusion: PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients.

Introduction: Comparing imaging examinations with those previously obtained is considered mandatory in imaging guidelines. To our knowledge, no studies are available on neither the influence, nor the sequence, of prior imaging and reports on diagnostic accuracy using biopsy as the reference standard. Such data are important to minimize diagnostic errors and to improve the preparation of diagnostic imaging guidelines. The aim of our study was to provide such data., Materials and Methods: A retrospective cohort of 216 consecutive skeletal biopsies from patients with at least 2 different imaging modalities (X-ray, CT and MRI) performed within 6 months of biopsy was identified. The diagnostic accuracy of the individual imaging modality was assessed. Finally, the possible influence of the sequence of imaging modalities was investigated., Results: No significant difference in the accuracy of the imaging modalities was shown, being preceded by another imaging modality or not. However, the sequence analyses indicate sequential biases, particularly if MRI was the first imaging modality., Conclusion: The sequence of the imaging modalities seems to influence the diagnostic accuracy against a pathology reference standard. Further studies are needed to establish evidence-based guidelines for the strategy of using previous imaging and reports to improve diagnostic accuracy.

Objective: To determine whether preoperative staging of high-risk prostate cancer with 18 F-sodium-fluoride ( 18 F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases., Design: Nationwide, population-based cohort study using real-world data., Setting: The study used national health registries, including all sites in Denmark from 2011 to 2018., Participants: Newly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either 18 F-NaF PET or bone scintigraphy., Main Outcome Measures: The risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival., Results: Between 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent 18 F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the 18 F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving 18 F-NaF PET and bone scintigraphy, respectively., Conclusion: Patients with high-risk prostate cancer undergoing preoperative staging with 18 F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups., Competing Interests: Competing interests: One author received grants from Bayer and Novo Nordisk for the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients., Methods: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0., Results: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively., Conclusion: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: Although volumetric imaging by computed tomography (CT) is the gold standard for preoperative assessment of the future liver remnant, nuclear imaging studies have shown promising data. This systematic review summarized the results from trials investigating volumetric and nuclear medicine imaging for the prediction of postoperative mortality and liver failure (LF)., Methods: MEDLINE and Web of Science were searched for papers investigating nuclear imaging methods for the prediction of postoperative clinical outcomes in patients undergoing local, liver-directed treatments. Only papers investigating both preoperative nuclear imaging and CT or magnetic resonance imaging (MR) for the prediction of postoperative mortality and/or LF were included., Results: Twenty-five trials were qualified for this review. All trials but two used technetium-based tracers for the nuclear imaging examination. Four papers used MR imaging and the remaining used CT for the volumetric evaluation. Overall, the studies were heterogeneous both in terms of methodology and imaging technique. Of the thirteen studies reporting on postoperative mortality, most were descriptive without detailed diagnostic data. A few with detailed data found that nuclear imaging had better predictive value than volumetric imaging. Nineteen studies investigated the prediction of postoperative LF of which seven papers investigated the predictive value of both modalities in multivariable regression analysis. Two papers found that only nuclear imaging parameters were predictive of LF, one paper found that the CT parameter was predictive, and four papers found that combined nuclear and CT/MR imaging parameters were predictive of LF., Conclusion: Both methodologies were useful in the preoperative assessment of patients scheduled for liver interventions, especially in combination, but nuclear imaging demonstrated better predictive value for postoperative mortality and LF in a few trials. The overall technical and methodological heterogeneity of the included studies complicates the ability to directly compare the clinical utility of the two imaging techniques., (© 2021. The Author(s).)

Background: The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies., Purpose: To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy., Material and Method: A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated., Results: 210 of 215 biopsies (98%; 95% CI 0.94-0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001-0.03), and three were equivocal (lack of imaging description)., Conclusion: Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Foundation Acta Radiologica 2021.)

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18 F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

Objective: Hepatobiliary scintigraphy (HBS) is an important tool in diagnosing biliary atresia in infants. There is limited evidence on the use of single photon emission computed tomography/computed tomography (SPECT/CT) as an additional imaging method to planar imaging. We evaluated the value of SPECT/CT in unclear cases of planar HBS., Subjects and Methods: Consecutive patients with suspected biliary atresia who underwent guideline-compliant HBS from January 2010 until March 2020 were reviewed, and cases with SPECT/CT were identified. Each step within the imaging procedure (dynamic, static [early and late], and SPECT/CT) was blindly reread in consensus by two observers and categorized based on a 5-point scale: 0, definitely no bowel excretion (i.e., atresia confirmed); 1, probably positive; 2,equivocal; 3, probably negative; and 4, definite negative (i.e., atresia not confirmed). In this analysis, categories were dichotomized as negative for biliary atresia (scores 3-4) or positive (scores 0-2, including equivocal scans). Available follow-up information constituted the standard of truth (SoT)., Results: Twenty-three infants had HBS, among which ten (4 boys and 6 girls; mean age 36 days; range 8-108) underwent SPECT/CT. Single photon emission computed tomography SPECT/CT was performed as early examination (<8h) in 3 subjects and late (8 to 24 h) in 7 infants. Reread SPECT/CT was categorized as positive for atresia in three infants and negative in seven infants. The SoT showed biliary atresia in one of ten patients. Single photon emission computed tomography/CT was true positive in one case, false positive in two, and true negative in seven. No false negative cases were noted. The diagnostic performance of SPECT/CT showed a sensitivity of 100%, specificity of 78%, positive predictive value (PPV) of 33%, negative predictive value (NPV) of 100%, and accuracy of 90%. For comparison, the diagnostic performance of planar HBS showed a sensitivity of 100%, specificity of 67%, PPV of 25%, NPV of 100%, and accuracy of 70%. In summary, the addition of SPECT/CT to planar HBS improved specificity andaccuracyand marginally improved PPV. Single photon emission computed tomography/CT provided more confidence in the final conclusion in 8/10 patients. In the remaining two cases, SPECT/CT did not improve the level of confidence (one remained equivocal, and one changed from probably no excretion to equivocal)., Conclusion: These preliminary data demonstrated increased accuracy of add-on SPECT to planar HBS predominantly due to improved specificity. This finding is consistent with the existing but limited literature and supports the recommendation of routine use of SPECT/CT or SPECT.

Objective: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria., Materials and Methods: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent., Results: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses., Conclusion: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

Objective: To evaluate the frequency and malignancy rate of incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the breast on PET/computed tomography (CT)., Material and Methods: All PET/CT scan reports from a single institution from 2010 to 2017 were electronically searched for words or phrases related to FDG uptake in the breast. Potentially eligible PET/CT scans were manually reviewed for the presence of focal incidental findings in the breast, and a final diagnosis was established based on pathology, clinical examinations, and clinical follow-up., Results: A total of 19 551 PET/CT scans were reviewed, from which 66 patients (0.3%) presented with unexpected focal FDG-avid lesions of the breast. Fifty-three patients (80.3%) had follow-up evaluations. The final diagnosis showed malignancies in 38 patients. Thirty-four patients had biopsy-verified cancer (primary breast cancers, n = 30; metastasis, n = 4), and four patients with known lymphoma showed a tumour response in the breast after chemotherapy. The malignancy rate was 85.0% among patients who underwent biopsy (34 of 40 patients). The SUVmax was significantly higher in patients with a final malignant diagnosis (n = 38) than in those with a benign diagnosis (n = 15) (4.5 ± 2.9 vs. 2.7 ± 1.3, P = 0.03)., Conclusion: Incidental uptake of FDG in the breast was rare. However, the malignancy rate was high among these patients, particularly among patients who had a follow-up biopsy. We recommend biopsy or thorough follow-up in patients with incidental focal uptake of FDG in the breast.

Background and study aims  Further diagnostics of incidental colorectal lesions on 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is questionable. Therefore, we aimed to evaluate the clinical importance of incidentally detected colorectal lesions on FDG-PET/CT. Patients and methods  In the North Denmark Region, a retrospective study was performed among 19,987 patients who had an FDG-PET/CT from January 2006 to December 2015. Among these patients, we identified patients with a colonoscopy within 12 months from the PET/CT scan and a description of incidental colorectal PET-avid lesions on the PET/CT. PET findings were compared with colonoscopy-detected lesions and eventually histopathology. Results  Incidental PET-avid lesions were observed in 549 patients. Colonoscopy revealed lesions in 457 (83 %), among whom 338 patients had a final histopathological diagnosis. Malignant and premalignant lesions were found in 297 patients (54 % among patients with a PET-avid lesion). The lesions were cancer in 76 patients and adenoma in 221 patients of whom 30 had high-grade and 191 low-grade adenomas. The findings changed patient management in 166 cases (30 % of all patients with a PET-avid lesion). A colonoscopy-based surveillance program was initiated for 80 % of patients with high-grade adenoma. No patients with PET-avid lesions but normal colonoscopy developed colorectal cancer during 3 years of observation (median observation time 7 years). Conclusions  Incidental colorectal FDG uptake was infrequently observed, but when present, it was associated with a high rate of malignant or premalignant lesions. Our results indicate that patients with incidental colorectal FDG uptake should be referred to diagnostic work-up including colonoscopy., Competing Interests: Competing interests Drs. Kousgaard, Petersen, and Thorlacius-Ussing have received grant support, un related to the study. Dr. Petersen has received fees for speaking at meetings arranged by Astellas Pharma, Sanofi-Genzyme, Janssen Pharma, and Bayer, and has been a paid participant at conferences organized by Sanofi-Genzyme and Bayer; and receives consulting fees from KLIFO Drug Development Council, Copenhagen and ljpmedical, Aalborg, Denmark., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objective: To investigate inter- and intraobserver agreement using standard (std)-single-photon emission computed tomography/computed tomography (SPECT/CT) or ultra-fast acquisition (UF)-SPECT/CT as an add-on to planar whole-body bone scintigraphy (WB-BS) for the detection of bone metastases in patients with known cancer., Methods: Images from patients (n = 104) participating in a prospective trial comparing SPECT/CT as an add-on to WB-BS with two different acquisition methods (std-SPECT/CT; 20 s per view, 32 views and UF-SPECT/CT; 16 views of 10 s per view) were included. The combinations of WB-BS with the two different SPECT/CT acquisition methods were independently evaluated by two experienced observers using a three-point scale (M0: no metastases, Me: equivocal for bone metastases and M1: bone metastases). The observers re-evaluated the scans 6 months later. Inter- and intraobserver agreement was calculated using linear weighted kappa., Results: The linear weighted kappa for the interobserver agreement was 0.78 [95% confidence interval (CI) 0.61-0.94] for WB-BS with std-SPECT/CT and 0.84 (95% CI 0.67-1.00) for WB-BS with UF-SPECT/CT. Similar values were observed for the intraobserver agreement, in which the linear weighted kappa was 0.76 (95% CI 0.60-0.92) and 0.73 (95% CI 0.57-0.90) for std-SPECT/CT and UF-SPECT/CT, respectively., Conclusion: Satisfactory inter- and intraobserver agreement was seen for both acquisition methods, emphasizing that the use of SPECT/CT as an add-on to WB-BS is a robust method for the detection of bone metastases even when conducted with a very short acquisition time.

Background: Several nuclear imaging methods may predict postoperative liver function and outcome, but none has achieved recommendations in clinical guidelines. The purpose of this systematic review was to summarize the existing knowledge on this topic., Methods: MEDLINE and Web of Science were searched for studies investigating nuclear medicine imaging methods for the prediction of postoperative liver function in patients undergoing localized, liver-directed treatments. The postoperative endpoints were clinical outcome (morbidity and mortality) as well as measures of postoperative liver function, e.g., liver function assessed by biochemical tests or nuclear imaging., Results: A total of 1352 references were identified, of which 82 fulfilled the eligibility criteria and were included in the review. Most studies (n = 63) were retrospective studies. The vast majority of studies assessed [ 99m Tc]Tc-galactosyl serum albumin (GSA) (n = 57) and [ 99m Tc]Tc-mebrofenin (n = 19). Liver resection was entirely or partly major (involved at least three segments) in 78 reports. There were notable variations in the research methodology, e.g., image acquisition, imaging variables, and endpoints. Thirty-seven studies reported on postoperative mortality, of which most reported descriptive data at the patient level. Of the four reports that performed multivariate analyses, two showed significant predictive results of isotope-based preoperative tests. Fifty-two papers presented data on postoperative liver failure. Multivariate predictive analyses were performed in eighteen trials, of which fifteen showed the significant value of nuclear medicine tests., Conclusion: There is sparse evidence supporting the significant value of nuclear medicine imaging methods in predicting postoperative mortality. In contrast, a notable number of trials showed a significant prediction of liver failure in multivariate analyses. The research methodology was heterogeneous and exploratory in most trials. Documentation of nuclear medicine tests in this setting awaits the results of properly designed, prospective trials with the standardization of both the nuclear medicine test and endpoints.

Objective: Gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga-PSMA PET/CT) has become a well-established imaging method for the evaluation of patients with prostate cancer. However, several cases have revealed PSMA uptake in a large variety of conditions other than prostate cancer. Prostate-specific membrane antigen uptake in thyroid cancer has also been reported. The aim of the present study was to systematically investigate the prevalence and clinical significance of thyroid incidental findings in patients undergoing 68 Ga-PSMA PET/CT., Materials and Methods: We retrospectively identified all patients referred for 68 Ga-PSMA PET/CT at the Department of Nuclear Medicine, Aalborg University Hospital, Denmark between May 2015 and May 2019. Patients with increased PSMA uptake in the thyroid gland were included in the analysis. Follow-up included imaging, biochemical, and/or histopathological collected over six months., Results: A total of 341 patients were included. Increased 68 Ga-PSMA uptake in the thyroid gland was observed in 13 patients (4%). Focal uptake was observed in seven patients, diffuse uptake in five patients and mixed focal and diffuse uptake in one patient. Malignancy was verified in two patients (2/13 patients, 15%), both patients with focal PSMA uptake., Conclusion: Gallium-68-PSMA thyroid incidental findings are rare in prostate cancer patients. However, cases of focal PSMA uptake in the thyroid gland should be further investigated, as these findings may represent metastatic or primary malignancy of the thyroid gland.

Background: Equivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics., Purpose: To investigate the reporting and handling of equivocal imaging findings in diagnostic studies of bone metastases, and to assess the impact on diagnostic performance of the methods used to analyze equivocal findings. The conceptual issue was reified based on two actual observations., Material and Methods: A recent meta-analysis of bone metastases in prostate cancer was conducted and data were obtained from a large clinical trial with a true reference of bone metastasis, where diagnostic characteristics were calculated with equivocal scans handled by: removal; considered malignant; considered benign; and intention-to-diagnose., Results: The meta-analysis included 18 trials where the median proportion of reported equivocal results was 27%. Eleven (61%) studies reported an equivocal option for the index test, 42% reported equivocal results and described how these were analyzed. The clinical trial included 583 prostate cancer patients with 20% equivocal results. The different methods of managing equivocal findings resulted in highly variable outcomes: sensitivity = 85%-100%; specificity = 78%-99%; and positive and negative predictive values = 44%-94% and 97%-100%, respectively. The diagnostic performances obtained using the four methods were differentially susceptible to the proportion of equivocal imaging findings and the prevalence of bone metastases., Conclusion: Reporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

Background: Several local ablative modalities have been introduced for the treatment of locally advanced pancreatic cancer (LAPC). However, there is no consensus on how to evaluate the imaging response after treatment. A systematic review was performed regarding the use of imaging for response assessment in LAPC., Methods: A systematic literature search was conducted in PubMed. Studies reporting imaging outcomes were included in the review. Studies were excluded if the imaging outcomes could not be differentiated between different disease stages, tumor histology or surgical approaches., Results: Thirty-four studies were included in the analysis. Fourteen studies used standardized response criteria, while six studies did not report the response evaluation method. The rest used self-determined criteria, absolute size comparisons or similar methods. One study found a correlation between early systemic progression (<6 months) and overall survival., Conclusion: There was notable variation in the use of imaging for response assessment in LAPC. This significantly hinders cross-comparison of results among studies. There is currently only sparse evidence of an association between imaging responses and overall survival. The field calls for standardized recommendations regarding the choice of response assessment method, timing of scans, target definition and reporting of outcomes., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the added value and diagnostic accuracy of 68 Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa)., Methods: Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68 Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68 Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference., Results: In total, 112 patients were included; 68 Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68 Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68 Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68 Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68 Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions., Conclusion: 68 Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings.

Background: The aim was to compare the diagnostic accuracy of 68 Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68 Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test., Results: Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68 Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68 Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68 Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68 Ga-PSMA PET/CT was 9-11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining., Conclusions: The sensitivity of 68 Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68 Ga-PSMA PET/CT and MRI/CT.

Our aim was to evaluate the interobserver agreement in 18 F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods: 18 F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the 18 F-NaF PET/CT scans on a patient level using a 3-category scale (no bone metastases [M0], equivocal for bone metastases, and bone metastases present [M1]) and on a dichotomous scale (M0/M1). In patients with no more than 10 lesions, the location and number of lesions were recorded. On a patient level, the diagnostic performance was calculated using a sensitivity analysis, in which equivocal lesions were handled as M0 as well as M1. Results: 18 F-NaF PET/CT scans from 219 patients with PCa were included, of whom 129 patients were scanned for primary staging, 67 for biochemical recurrence, and 23 for metastatic castration-resistant PCa. Agreement between the observers was almost perfect on a patient level (3-category unweighted κ = 0.83 ± 0.05, linear weighted κ = 0.90 ± 0.06, and dichotomous κ = 0.91 ± 0.07). On a lesion level (dichotomous scale), the observers agreed on the number and location of bone metastases in 205 (93.6%) patients. In the remaining 14 patients, the readers disagreed on the number of lesions in 13 patients and the location of bone metastases in 1 patient. A final diagnosis of bone metastases was made for 211 of 219 patients. The sensitivity ranged from 0.86 to 0.92, specificity from 0.83 to 0.97, positive predictive value from 0.70 to 0.93, and negative predictive value from 0.94 to 0.96. Conclusion: The interobserver agreement on 18 F-NaF PET/CT for the detection of bone metastases in patients with PCa was very high among trained observers, both on a patient level and on a lesion level. Moreover, the diagnostic performance of 18 F-NaF PET/CT was satisfactory, rendering 18 F-NaF PET/CT a robust tool in the diagnostic armamentarium., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a reference test., Methods: A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopathology. The trials must have diagnostic data on a patient level., Results: Eighteen eligible clinical trials included 969 patients. The median patient number per study was 32 (range 10 to 208). Five trials were prospective, and nine trials had a consecutive enrolment of patients. Sixteen studies used Ga-68-PSMA-11; there was one study with Cu-64-PSMA and one study with F-18-DCDFPyL. Twelve studies used PET/CT, four trials used PET/MR. Most trials included patients with intermediate and high-risk. Diagnostic accuracy varied notably among the studies; sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%. Weighted sensitivity was 59%, weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI); in all cases, sensitivity and specificity were superior with PSMA PET. Three studies compared PSMA PET with multi-parametric or diffusion-weighted MRI with mixed results., Conclusions: PSMA PET showed promising diagnostic accuracy for primary lymph node staging with pathology as reference. Recommendation for PSMA PET for high-risk patients in clinical guidelines should be supported by confirmatory, prospective trials with patient-relevant outcomes.

Ga-PSMA PET/CT has become a well-established imaging modality to detect prostate cancer (PCa) metastases in biochemical recurrence. Despite its claimed specificity for PCa, Ga-PSMA uptake in tissues unrelated to PCa, particularly in the neovascular tissue of other cancers, has been reported in numerous studies. A 73-year-old man underwent Ga-PSMA PET/CT for biochemical recurrence of PCa 7 years after radical prostatectomy. The Ga-PSMA PET/CT showed 1 lesion with PSMA uptake in the distal left ureter. Histology revealed a low-grade noninvasive papillary urothelial carcinoma. By immunohistochemistry, PSMA expression was observed in the neoplastic urothelial cells and in the vessels of the papillary structures.

The aim of this study was to determine if additional 18 F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels < 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level ≥ 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Both 99m Tc-DTPA and 51 Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51 Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99m Tc-DTPA and 51 Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51 Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99m Tc-DTPA (CaNa 3 -DTPA) and 2.5 MBq 51 Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m 2 . No patients suffered from ascites or significant oedema. The mean 51 Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated ( r  = 0.993). The plasma clearance was significantly higher when measured by 99m Tc-DTPA than by 51 Cr-EDTA ( p  = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99m Tc-DTPA and that of 51 Cr-EDTA. Therefore, 99m Tc-DTPA can replace 51 Cr-EDTA when needed.

Background and Aims: Classically, peripheral arterial disease (PAD) is diagnosed by a low ankle-brachial index (ABI), but the diagnosis can also be made based on toe-brachial index (TBI) measurements. The objective of this study was to characterize patients with low TBI but normal ABI, and chart potential underestimation of PAD prevalence by solitary use of ABI., Methods: A total of 3739 consecutive patients with known or suspected PAD referred for ABI and TBI measurements in a four-year period were compared to an age- and gender matched control group (n = 17,340)., Results: In the patient cohort, 65.0% had low ABI, 20.5% had low TBI but normal ABI, and 14.5% had normal indices. When comparing the frequencies of comorbidities related to atherosclerotic disease (myocardial infarction, congestive heart failure, cerebrovascular disease, diabetes mellitus, chronic kidney failure), there were no significant differences among patients with low ABI or low TBI with normal ABI in any of the variables (all p > 0.06). Of the patients with low TBI and normal ABI, 18.7% were diagnosed with diabetes mellitus type I or II, and 8.2% with chronic kidney disease., Conclusions: Patients with low TBI but normal ABI represented 20.5% of patients referred with the suspicion of PAD. Furthermore, patients with low TBI but normal ABI presented similar comorbid characteristics to patients with low ABI, who have a well-described increased risk of cardiovascular morbidity and mortality. The solitary use of ABI underestimated the prevalence of PAD in the population, and PAD screening could potentially be improved by routine application of TBI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Semi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication., Materials and Methods: Quantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV 2.5 (SUV 2.5 cut-off) and MTV 41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTV VAS ) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss' kappa for multiple observers., Results: In the quantitative analysis, a ROC-determined MTV 2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV 41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss' kappa 0.47). MTV VAS and eMTV were not consistently correlated with the outcome., Conclusion: Predictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.

Ventilation/perfusion single-photon emission computed tomography performed using an aerosol of carbon-coated technetium is frequently used for diagnosing pulmonary embolism. Certain patients may suffer from chronic obstructive pulmonary disease (COPD); for such patients, the formation of mucus clots in airways can cause accumulation of the aerosol in the larger airways. This centralized deposition of the aerosol leads to insufficient activity in peripheral lung segments and subsequently results in ventilation images of substandard or even nondiagnostic quality. Continuous positive airway pressure (CPAP) therapy improves airway dynamics and quality of life for COPD patients. We report for the first time the results for two patients for whom initial ventilation scans were of insufficient quality, but diagnostic-quality images were obtained after CPAP therapy., Competing Interests: There are no conflicts of interest.

A 69-year-old man with newly diagnosed prostate cancer PSA 274 ng/mL, Gleason 4+3, T-stage 3b) underwent Ga-PSMA PET/CT for staging with follow-up scans 6 and 13 weeks after androgen deprivation therapy (ADT) initiation. Six weeks after ADT initiation, lymph node metastases observed at staging showed metabolic and radiological regression, whereas the skeleton showed increased PSMA uptake in existing bone metastases and several new PSMA-avid lesions. Skeletal PSMA uptake decreased after 13 weeks of ADT, and prostate-specific antigen decreased to 16 ng/mL. These findings suggest the presence of the flare phenomenon to ADT in bone metastases seen on PSMA PET/CT.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To prospectively compare diagnostic accuracies for detection of bone metastases by 68 Ga-PSMA PET/CT, 18 F-NaF PET/CT and diffusion-weighted MRI (DW 600 -MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR)., Methods: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68 Ga-PSMA PET/CT, a 18 F-NaF PET/CT and a DW 600 -MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm 2 ). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic., Results: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68 Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18 NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW 600 -MRI (n = 60 patients). The diagnostic performance of DW 600 -MRI was significantly lower than that of 68 Ga-PSMA PET/CT and 18 NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68 Ga-PSMA PET/CT and 18 NaF PET/CT (p = 0.65)., Conclusion: 68 Ga-PSMA PET/CT and 18 F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW 600 -MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Aim: To compare 18 F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99m Tc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment., Material and Methods: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses., Results: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy., Conclusion: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

Purpose of the Report: The aim of this study was to prospectively investigate the detection rate of Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management., Materials and Methods: Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a Ga-PSMA PET/CT. Changes in patient management based on the results of Ga-PSMA PET/CT were assessed., Results: Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, Ga-PSMA PET/CT guided the choice of treatment., Conclusions: Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (<0.5 ng/mL) were notably below the values reported in previous retrospective studies; however, detection rates improved with increasing PSA levels.

Incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the thyroid on positron emission tomography (PET/CT) is rare but often associated with malignancy. The epidemiology of thyroid incidentalomas has only to some extent been described in countries with iodine deficiency. Here we report data from Denmark, a country with known iodine deficiency and wide access to PET/CT. All FDG PET/CT comprising the head and neck region, during 2014, were retrospectively reviewed, and patients with focal FDG uptake in the thyroid gland were identified. A total of 2451 patients had an FDG PET/CT of which 59 (2.4%) patients presented with FDG-avid focal lesions in the thyroid gland. Among the 59 patients with FDG-avid lesions, 33 patients (56%) received work up with ultrasound, thyroid technetium scintigraphy, fine needle aspiration, and/or histology of which 20 patients had a conclusive pathology report. Ten patients with FDG-avid lesions were identified with thyroid malignancy. The risk of thyroid malignancy was 16.9% among patient with incidental FDG-avid thyroid lesions. Our findings indicated a similar frequency of FDG thyroid incidentalomas and malignancy rates in an iodine deficient population compared to summary data from prior studies, studies mostly performed in geographical areas of normal or excess iodine supplementation.

Objective: The aim of this study was to investigate the contribution of contrast-enhanced computed tomography (CE-CT) to the localization of parathyroid adenomas compared with the dual-phase Tc-99m MIBI SPECT with low-dose CT (LD-CT)., Patients and Methods: This retrospective study included consecutive patients with primary hyperparathyroidism who underwent a preoperative dual-phase MIBI SPECT/CT followed by surgical resection. The standard of care was dual-phase MIBI SPECT/CT, acquired with LD-CT in the early phase and CE-CT in the late phase (SPECT/CE-CT). The presence and localization of positive sites were extracted from study reports. To examine the role of CE-CT, patient cases were independently re-reviewed, with the early LD-CT fused with early and late SPECT (SPECT/LD-CT). The two SPECT/CT methods were compared for sensitivity, and the positive predictive value and histopathology were used as a reference., Results: In total, 138 patients were included. The investigation was positive for suspected adenomas in 124 patients using SPECT/CE-CT and in 122 patients using SPECT/LD-CT. The per-patient sensitivity was 87.5% [95% confidence interval (CI): 80.7-92.6%] for SPECT/CE-CT and was not statistically significantly different from SPECT/LD-CT (85.3%; 95% CI: 78.2-90.8%) (P=0.39). The positive predictive value was 95.2% (95% CI: 95.4-99.9%) with SPECT/CE-CT versus 100% (95% CI: 96.8-100%) with SPECT/LD-CT. For small adenomas (≤500 mg), the sensitivity was low with SPECT/CE-CT (67%) as well as with SPECT/LD-CT (64%)., Conclusion: Late CE-CT, compared with late LD-CT, did not significantly improve the sensitivity of dual-phase Tc-99m MIBI parathyroid SPECT/CT in a population of patients with primary hyperparathyroidism. These findings were consistent regardless of the size, location, or histology of the adenomas.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes on current therapy. We investigated whether response assessed with PET/CT combined with baseline total metabolic tumor volume (TMTV) could detect early relapse or refractory disease. Methods: From 7 European centers, 140 patients with nodal PTCL who underwent baseline PET/CT were selected. Forty-three had interim PET (iPET) performed after 2 cycles (iPET2), 95 had iPET performed after 3 or 4 cycles (iPET3/4), and 96 had end-of-treatment PET (eotPET). Baseline TMTV was computed with a 41% SUV max threshold, and PET response was reported using the Deauville 5-point scale. Results: With a median of 43 mo of follow-up, the 2-y progression-free survival (PFS) and overall survival (OS) were 51% and 67%, respectively. iPET2-positive patients (Deauville score ≥ 4) had a significantly worse outcome than iPET2-negative patients ( P < 0.0001, hazard ratio of 6.8 for PFS; P < 0.0001, hazard ratio of 6.6 for OS). The value of iPET3/4 was also confirmed for PFS ( P < 0.0001) and OS ( P < 0.0001). The 2-y PFS and OS for iPET3/4-positive ( n = 28) and iPET3/4-negative ( n = 67) patients were 16% and 32% versus 75% and 85%, respectively. The eotPET results also reflected patient outcome. A model combining TMTV and iPET3/4 stratified the population into distinct risk groups (TMTV ≤ 230 cm 3 and iPET3/4-negative [2-y PFS/OS, 79%/85%]; TMTV > 230 cm 3 and iPET3/4-negative [59%/84%]; TMTV ≤ 230 cm 3 and iPET3/4-positive [42%/50%]; TMTV > 230 cm 3 and iPET3/4-positive [0%/18%]). Conclusion: iPET response is predictive of outcome and allows early detection of high-risk PTCL patients. Combining iPET with TMTV improves risk stratification in individual patients., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials ( n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study ( p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients., Competing Interests: There are no competing interests in this manuscript. Lars J. Petersen and Helle D. Zacho received grant support. Lars J. Petersen received fees for speaking at meetings arranged by Sanofi-Genzyme, Janssen Pharma, and Bayer; has been a paid participant in conferences by Sanofi-Genzyme and Bayer; and receives consulting fees from KLIFO Drug Development Council.

Background: The aim of this study is to assess whether ultra-fast acquisition SPECT/CT (UF-SPECT/CT) can replace standard SPECT/CT (std-SPECT/CT) as "add-on" to whole-body bone scintigraphy (WB-BS) for the investigation of bone metastases. Consecutive cancer patients referred for WB-BS who underwent SPECT/CT in addition to WB-BS were included. Std-SPECT, UF-SPECT, and low-dose CT were performed (std-SPECT: matrix 128 × 128, zoom factor 1, 20 s/view, 32 views; UF-SPECT: identical parameters except for 10 s/view and 16 views, reducing the acquisition time from 11 to 3 min). A consensus diagnosis was reached by two observers for each set of images (WB-BS + standard SPECT/CT or WB-BS + UF-SPECT/CT) using a three-category evaluation scale: M0: no bone metastases; M1: bone metastases; and Me: equivocal findings., Results: Among the 104 included patients, most presented with prostate cancer (n = 71) or breast cancer (n = 28). Using WB-BS + std-SPECT/CT, 71 (68%) patients were classified as M0, 19 (18%) as M1, and 14 (14%) as Me. Excellent agreement was observed between WB-BS + std-SPECT/CT and WB-BS + UF-SPECT/CT using the three-category scale: kappa = 0.91 (95% CI 0.84-0.97). No difference in observer agreement between cancer types was detected. SPECT/CT provided a definitive classification in 90 of 104 cases in which WB-BS was not entirely diagnostic., Conclusions: To investigate potential bone metastases, UF-SPECT/CT can be conducted as add-on to WB-BS to notably reduce the SPECT acquisition time without compromising diagnostic confidence.