Median Standardized Uptake Value Research Articles

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

BackgroundThe pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium. ObjectivesThis study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM. MethodsForty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups. ResultsATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, β = 0.139, P < 0.001), native T1 time (r = 0.432, β = 0.020, P = 0.005), RV-LS (r = 0.445, β = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, β = 2.842, P = 0.003), troponin T (r = 0.422, β = 0.048, P = 0.007), 6MWD (r = 0.385, β = −0.007, P = 0.017), and NAC stage (r = 0.490, β = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021). ConclusionsIn ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

Towards improved diagnosis: radiomics and quantitative biomarkers in 18 F-PSMA-1007 and 18 F-fluorocholine PET/CT for prostate cancer recurrence.

This study compared the radiomic features and quantitative biomarkers of 18 F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18 F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUV mean , PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUV max value was significantly higher for 18 F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUV mean , TL-PSMA/FCH, and PSMA/FCH-TV between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUV mean /SUV max and PSA level was moderate, both for 18 F-PSMA ( r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH ( r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18 F-PSMA ( r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH ( r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUV max values for both radiotracers compared with those who did not, the difference was statistically significant only for 18 F-PSMA ( P < 0.05). Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18 F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/μL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

Associations of galectin-3 levels with measures of vascular disease in patients with rheumatoid arthritis

ObjectivesGalectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA). MethodsRA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic SUV, and MFR. ResultsA total of 124 RA patients (mean age 57; 82 % women, 45 % Hispanic; median RA duration 6.8 years; 75 % seropositive; median CDAI 16; 33 % on prednisone; 89 % on DMARDs; median CAC score 0; median aorta SUV 2.59; mean MFR 2.86; median galectin-3 level 8.54 ng/mL) were analyzed. In univariable analysis, higher galectin-3 levels were associated with higher aortic SUV (p = 0.007) but CAC score and MFR were not. In multivariable analysis, higher galectin-3 level remained significantly associated with higher aortic SUV (ß Coefficient=0.1786, p value=0.002). ConclusionIn our cohort of RA patients without clinical CVD, higher serum galectin-3 levels were independently associated with higher levels of aortic inflammation, but not CAC score or MFR. This suggests that galectin-3 may be a biomarker for an inflammatory and potentially reversible stage, but not a later (calcified) stage, of atherosclerosis in patients with RA.

Reduction of Metabolic Active Tumor Volume Prior to CAR T-Cell Therapy Improves Survival Outcomes in Patients with Large B-Cell Lymphoma

Introduction CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become the standard 2 nd or 3 rd line therapy for patients with relapsed or refractory Large B-cell lymphoma (r/r LBCL). As part of this treatment bridging therapy is frequently used between T-cell apheresis and CAR T-cell infusion in order to limit disease progression, diminish lymphoma-related symptoms and/or reduce tumor volume. Bridging therapy has shown to be feasible, safe and effective in patients prior to infusion. In addition, a lower tumor volume is associated with better treatment outcomes and less toxicity. However, the exact reduction and dynamics in metabolic active tumor volume (MATV) are unknown. Here we investigated the relation of changes in pre-apheresis (baseline) MATV, based on 18F-FDG PET scans, and pre-lymphodepleting chemotherapy (pre-LD) MATV with CAR T-cell outcomes and toxicities in patients with r/r LBCL. Methods Baseline and pre-LD MATVs and PET characteristics were calculated semi-automatically of patients who were treated with CAR T-cell therapy. A Standardized Uptake Value (SUV) threshold of 2.5 was used to maintain robustness and avoid MATV underestimation. Bridging strategies consisted of radiotherapy, chemotherapy, or a combination of both. Primary endpoints were duration of response (DOR) and overall survival (OS). Secondary endpoints included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The Youden index was used to identify the optimal cut-off for dividing patients into low- and high-MATV groups to predict DOR at 2 years. Two-year DOR and OS rates were estimated using Kaplan-Meier curves and the log-rank test was utilized to compare the differences among low- and high-MATV patient groups. Univariable analysis was performed with Cox regression for DOR and OS, and with logistic regression for CRS and ICANS. Results Seventy-four patients with LBCL and treated with CAR T-cell therapy were included in the study. For all patients baseline 18F-FDG PET scans were available, whereof in 68 patients the pre-LD scans. The median baseline MATV was 180 cc (IQR 64 - 426) with a median SUV max of 18.8 (IQR 11.9 - 28.1) and increased to 241 cc (IQR 75 - 525) at pre-LD, with a median SUV max of 21.0 (IQR 12.8 - 31.3). The optimal cut-offs for low- and high-MATV patient groups at baseline and pre-LD were 190 cc and 480 cc, respectively. Patients with a low MATV baseline had a better DOR (Figure 1A) and OS compared to high MATV baseline patients (both p &amp;lt; 0.001). Patients with a high MATV baseline that was reduced to a low MATV pre-LD showed a significant improvement in DOR (Figure 1B) and OS, compared to patients with a high MATV pre-LD ( p = 0.036 for DOR; p = 0.015 for OS). Univariable analysis showed that a high baseline MATV was associated with a worse DOR (HR 6.43 CI [2.15 - 19.20]; p &amp;lt; 0.001) and OS (HR 6.97 CI [2.33 - 20.80]; p &amp;lt; 0.001). A high pre-LD MATV was also associated with a worse DOR (HR 4.86 CI [1.98 - 12.00]; p &amp;lt; 0.001) and OS (HR 5.87 [2.41 - 14.30]; p &amp;lt; 0.001). Other significant associations with DOR and OS were observed for pre-LD lactate dehydrogenase (LDH), the IPI score for DOR exclusively, and gender and bridging therapy for OS exclusively. Conclusions We showed that patients with a low MATV compared to a high MATV at baseline have better survival outcomes and less toxicity. Additionally, reducing tumor volume by applying bridging therapy in patients with a high baseline MATV, results in a significant better DOR and OS. Reducing the MATV before CAR T-cell infusion is therefore essential in CAR T-cell therapy patient care and provides a rationale for the use of more intensive bridging therapies.

Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers.

In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [18F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT in patients with RAI-R-FCTC. In this retrospective study, a total of 117 patients with RAI-R-FCTC were included. The study population consisted of 68 females and 49 males, with a mean age of 53.2 ± 11.7 years. The aim of the study was to perform a comprehensive qualitative and quantitative assessment of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT scans in RAI-R-FCTC patients. The qualitative assessment involved comparing patient-based and lesion-based visual interpretations of both scans, while the quantitative assessment included analyzing standardized uptake values corrected for lean body mass (SULpeak and SULavg). The findings obtained from the scans were validated by correlating them with morphological findings from diagnostic computed tomography and/or histopathological examination. Among the 117 RAI-R-FCTC patients, 60 had unilateral local disease, and 9 had bilateral lesions with complete concordance in the detection rate on both PET scans. [68Ga]Ga-DOTA.SA.FAPi had a higher detection rate for lymph nodes (95.4% vs 86.6%, p<0.0001), liver metastases (100% vs. 81.3%, p<0.0001), and brain metastases (100% vs. 39%, p<0.0001) compared to [18F]F-FDG. The detection rates for pleural and bone metastases were similar between the two radiotracers. For lung metastases, [68Ga]Ga-DOTA.SA.FAPi showed a detection rate of 81.7%, whereas [18F]F-FDG had a detection rate of 64.6%. Remarkably, [68Ga]Ga-DOTA.SA.FAPi was able to detect a bowel metastasis that was missed on [18F]F-FDG scan. The median standardized uptake values (SUL) were generally comparable between the two radiotracers, except for brain metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 13.9 vs. 6.7, p-0.0001) and muscle metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 9.56 vs. 5.62, p-0.0085), where [68Ga]Ga-DOTA.SA.FAPi exhibited higher uptake. The study results demonstrate the superior performance of [68Ga]Ga-DOTA.SA.FAPi compared to [18F]F-FDG PET/CT in detecting lymph nodal, liver, bowel, and brain metastases in patients with RAI-R-FCTC. These findings highlight the potential of [68Ga]Ga-DOTA.SA.FAPi as a theranostic tool that can complement the benefits of [18F]F-FDG PET/CT in the imaging of RAI-R-FCTC.

Diagnostic value of two-time point [68Ga]Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer

The emerging PET tracer [68Ga]Ga-PSMA-11 has been established for staging in prostate cancer (PCa). Aim was to determine the value of early static imaging in two-phase PET/CT. 100 men with newly diagnosed histopathologically confirmed untreated PCa who underwent [68Ga]Ga-PSMA-11 PET/CT from January 2017 to October 2019 were included. The two-phase imaging protocol consisted of an early static scan of the pelvis (6 min p.i.) and a late total-body scan (60 min p.i). Associations of semi-quantitative parameters derived via volumes of interest (VOI) with Gleason grade group and PSA were investigated. In 94/100 patients (94%) the primary tumor was detected in both phases. In 29/100 patients (29%) metastases were detected at a median PSA level of 32.2 ng/ml (0.41–503 ng/ml). In 71/100 patients (71%) without metastasis a median PSA level of 10.1 ng/ml (0.57–103 ng/ml) was observed (p = < 0.001). Primary tumors demonstrated a median standard uptake value maximum (SUVmax) of 8.2 (3.1–45.3) in early phase versus 12.2 (3.1–73.4) in late phase and a median standard uptake value mean (SUVmean) of 4.2 (1.6–24.1) in early phase versus 5.8 (1.6–39.9) in late phase, significantly increasing over time (p = < 0.001). Higher SUVmax and SUVmean were associated with higher Gleason grade group (p = 0.004 and p = 0.003, respectively) and higher PSA levels (p = < 0.001). In 13/100 patients the semi-quantitative parameters including SUVmax were declining in the late phase compared to early phase. Two-phase [68Ga]Ga-PSMA-11 PET/CT demonstrates a high detection rate for primary tumor of untreated PCa of 94% and improves diagnostic accuracy. Higher PSA levels and Gleason grade group are associated with higher semi-quantitative parameters in the primary tumor. Early imaging provides additional information in a small sub-group with declining semi-quantitative parameters in the late phase.

Oxidized Regenerated Cellulose can be a Cause of False Tumor Recurrence on PET/CT in Patients with Lung Cancer Treated Surgically.

Regular follow-up of patients with lung cancer treated surgically is crucial to detect local recurrence or distant metastasis of the tumor. Postoperative follow-ups are performed with thorax computed tomography (CT) and, if necessary, positron emission tomography (PET)/CT. Sometimes, inflammatory tissue reactions due to the materials used during the surgery for hemostasis may cause the appearance of tumor recurrence in imaging modalities. In this study, we presented that oxidized regenerated cellulose (ORC) used intraoperatively may cause false tumor recurrence on PET/CT. The records of patients who had local tumor recurrence after lung cancer surgery was reviewed retrospectively. Inclusion criteria were the presence of local recurrence of cancer on PET/CT, specification of using ORC in the surgical notes, and histopathological diagnosis of the recurrence site of tumor was reported as a foreign body reaction. Data of patients were collected according to age, gender, surgery performed, adjuvant therapy status, resolution status and time ORC, and standard uptake value of 18F-fluorodeoxyglucose on PET/CT. Eleven patients (1 female, 10 males) who met the criteria were included in the study. The median age was 64. Histopathological results of all patients were reported as foreign body reactions. The median detection time of PET/CT positivity after surgery was 139 days (range: 52-208 days). False tumor recurrence was resolved in 8 patients (72.7%) in their control radiological examinations and median resolution time was 334 days (range: 222-762 days). The median maximum standard uptake value of the lesions was 6.2 (1.7-11) on the PET/CT. ORC used intraoperatively in patients undergoing surgery for lung cancer may cause false tumor recurrence in imaging modalities in postsurgical follow-ups. When tumor recurrence is suspected in the follow-up of these patients, histopathological confirmation is necessary to prevent unnecessary operations and treatments.

Bridging Radiation Rapidly and Effectively Cytoreduces High-Risk Relapsed/Refractory Aggressive B Cell Lymphomas Prior to Chimeric Antigen Receptor T Cell Therapy

Greater tumor burden before CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy predicts lower complete response rate and shorter overall survival (OS) in patients with aggressive non-Hodgkin lymphoma (NHL). Recent patterns of failure studies have identified lesion characteristics, including size, standard uptake value (SUV), and extranodal location, as associated with post-CAR-T therapy failure. Here we analyzed the effect of bridging radiation-containing treatment (BRT) on pre-CAR-T therapy lesion- and patient-level characteristics and post-CAR-T therapy outcomes, including patterns of failure. Consecutive NHL patients who received radiation therapy from 30 days before leukapheresis until CAR T cell infusion were reviewed. Metabolic tumor volume (MTV) was contoured with a threshold SUV of 4. The first post-CAR-T therapy failures were categorized as preexisting/new/mixed with respect to pre-CAR-T therapy disease and in-field/marginal/distant with respect to BRT. Forty-one patients with diffuse large B cell lymphoma (DLBCL; n=33), mantle cell lymphoma (n=7), or Burkitt lymphoma (n=1) were identified. BRT significantly improved established high-risk parameters of post-CAR-T therapy progression, including in-field median MTV (45.5 cc to .2 cc; P < .001), maximum SUV (18.1 to 4.4; P < .001), diameter (5.5 cm to 3.2 cm; P < .001), and lactate dehydrogenase (LDH; 312 to 232; P=.025). DLBCL patients with lower LDH levels post-BRT had improved progression-free survival (PFS; P=.001). In DLBCL, first failures were new in 7 of 19 patients, preexisting in 5 of 19, and mixed in 7 of 19; with respect to BRT, 4 of 19 were in-field and 4 of 19 were marginal. Post-CAR-T therapy survival was similar in patients with initially low MTV and those with newly low MTV post-BRT using a statistically determined threshold of 16 cc (PFS, 26 months versus 31 months; OS unreached for both). BRT produced significant cytoreductions in diameter, SUV, MTV, and LDH, all predictors of poor post-CAR-T therapy outcomes. Similar PFS and OS in patients with initially low MTV and those who achieved newly low MTV after BRT suggest that BRT may "convert" poor-risk patients to better risk. In the future, the response to BRT may allow for risk stratification and individualization of bridging strategies.

Experimental non-alcoholic fatty liver disease causes regional liver functional deficits as measured by the capacity for galactose metabolism while whole liver function is preserved

BackgroundIncreasing incidence of non-alcoholic fatty liver disease (NAFLD) calls for improved understanding of how the disease affects metabolic liver function.AimsTo investigate in vivo effects of different NAFLD stages on metabolic liver function, quantified as regional and total capacity for galactose metabolism in a NAFLD model.MethodsMale Sprague Dawley rats were fed a high-fat, high-cholesterol diet for 1 or 12 weeks, modelling early or late NAFLD, respectively. Each NAFLD group (n = 8 each) had a control group on standard chow (n = 8 each). Metabolic liver function was assessed by 2-[18F]fluoro‐2‐deoxy‐D-galactose positron emission tomography; regional galactose metabolism was assessed as standardised uptake value (SUV). Liver tissue was harvested for histology and fat quantification.ResultsEarly NAFLD had median 18% fat by liver volume. Late NAFLD had median 32% fat and varying features of non-alcoholic steatohepatitis (NASH). Median SUV reflecting regional galactose metabolism was reduced in early NAFLD (9.8) and more so in late NAFLD (7.4; p = 0.02), both significantly lower than in controls (12.5). In early NAFLD, lower SUV was quantitatively explained by fat infiltration. In late NAFLD, the SUV decrease was beyond that attributable to fat; probably related to structural NASH features. Total capacity for galactose elimination was intact in both groups, which in late NAFLD was attained by increased fat-free liver mass to 21 g, versus 15 g in early NAFLD and controls (both p ≤ 0.002).ConclusionRegional metabolic liver function was compromised in NAFLD by fat infiltration and structural changes. Still, whole liver metabolic function was preserved in late NAFLD by a marked increase in the fat-free liver mass.

Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial

Immune checkpoint inhibitors (ICIs), by reinvigorating CD8+ T cell mediated immunity, have revolutionized cancer therapy. Yet, the systemic CD8+ T cell distribution, a potential biomarker of ICI response, remains poorly characterized. We assessed safety, imaging dose and timing, pharmacokinetics and immunogenicity of zirconium-89-labeled, CD8-specific, one-armed antibody positron emission tomography tracer 89ZED88082A in patients with solid tumors before and ~30 days after starting ICI therapy (NCT04029181). No tracer-related side effects occurred. Positron emission tomography imaging with 10 mg antibody revealed 89ZED88082A uptake in normal lymphoid tissues, and tumor lesions across the body varying within and between patients two days after tracer injection (n = 38, median patient maximum standard uptake value (SUVmax) 5.2, IQI 4.0–7.4). Higher SUVmax was associated with mismatch repair deficiency and longer overall survival. Uptake was higher in lesions with stromal/inflamed than desert immunophenotype. Tissue radioactivity was localized to areas with immunohistochemically confirmed CD8 expression. Re-imaging patients on treatment showed no change in average (geometric mean) tumor tracer uptake compared to baseline, but individual lesions showed diverse changes independent of tumor response. The imaging data suggest enormous heterogeneity in CD8+ T cell distribution and pharmacodynamics within and between patients. In conclusion, 89ZED88082A can characterize the complex dynamics of CD8+ T cells in the context of ICIs, and may inform immunotherapeutic treatments.

Clinical features and treatment outcomes of pulmonary actinomycosis.

Pulmonary actinomycosis is a rare and chronic infectious disease that mimics malignancy and is frequently misdiagnosed. There are few reports that address the clinical characteristics of pulmonary actinomycosis. The objective of this research is to evaluate the clinical features, radiological findings, diagnostic approaches and treatment outcomes of pulmonary actinomycosis. Thirty-seven patients with pulmonary actinomycosis histopathologically diagnosed from 2009 to 2021 were analyzed retrospectively. The mean age at presentation was 53.7 (±13.3) years. Frequent symptoms were cough and hemoptysis. The median diagnosis time from the first symptoms was 60 days (interquartile range 18-195). Pulmonary comorbidity was found in 59.5% of cases. The most common thorax computed tomography finding was mass or nodule. The low-attenuation center within the mass or consolidation was observed in 40% of the lesions. The median maximal standardized uptake value of lesions on positron emission tomography (PET) was 6.5 (interquartile range 2.7-10.3). In the majority of cases (97.3%), the diagnosis of pulmonary actinomycosis was not suspected at admission, and 56.8% of patients were misdiagnosed with lung cancer. The mean duration of antibiotic therapy was 9.4 days (range 3-22) with intravenous antibiotics and 64.7 days (range 5-270) with oral antibiotics. Four patients died due to concomitant comorbidities. Eight cases were lost to follow-up. All other cases were fully cured. Pulmonary actinomycosis mimics other diseases, often lung cancer. Clinicians should consider the diagnosis of actinomycosis when they detect a mass or consolidation, especially with a low-attenuation center. PET/CT appears not to be useful for differential diagnosis. A shorter course of antibiotic therapy than traditionally recommended appears to be sufficient.

MRI- and PET-Based Assessment of Radiological and Clinical Factors Associated With Cervical Cancer Response to External Beam Radiation Therapy.

Introduction In the era of MRI-guided external beam radiation therapy (EBRT), complete radiological response (CR) is often seen in cervical cancer (CC) with 4-6 weeks of chemotherapy and EBRT. The clinical and radiological factors associated with this observation were investigated in this study. Materials and methods One hundred and twenty-four CC patients treated with concurrent chemotherapy, EBRT, and brachytherapy (BT) from January 2008 to July 2015 were retrospectively screened. Initial primary gross tumor volume (GTVINITIAL) was estimated after contouring on a planning CT scan registered with pre-EBRT PET and MRI. The maximum standardized uptake value (SUV) of GTVINITIAL from each PET scan report was collected. Spearman's rank correlation coefficient (rho) values were calculated to assess the relationships among age, tumor size, and SUV. Tumor radiological response during EBRT prior to BT was calculated by contouring the final primary gross tumor volume (GTVFINAL) using MRI obtained prior to BT. CRrates during EBRT were estimated from GTVINITIAL and GTVFINAL and compared by the level of various factors using Fisher's exact test (two-sided). Results Forty-eight patients met the inclusion criteria of the study with a median age of 50 years. The median GTVINITIAL was 82 cc. The median SUV was 14.9. A significant correlation was seen between SUV and GTVINITIAL with a larger tumor size associated with a higher SUV. CR rates were numerically higher for patients who were aged <50 years, or with >37.5 Gy radiation dose at or before the second MRI, or with GTVINITIAL <100 cc, or with no nodes involved or with stages IB or IIA. Conclusions Our study identified higher CC primary tumor CR rates during EBRT in younger patients (<50) with smaller tumors (100 cc) without nodal involvements as well as a positive correlation between PET FDG (18F-fluorodeoxyglucose)-SUV and CC primary tumor size.

Predicting the Recurrence of Gastric Cancer Using the Textural Features of Perigastric Adipose Tissue on [18F]FDG PET/CT.

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.

68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma.

PurposeHigh-grade gliomas (HGG) are still associated with a dismal prognosis. Prostate specific membrane antigen (PSMA) is discussed as a theranostic target for PSMA-directed radioligand therapy ([177Lu]Lu-PSMA RLT). Here, we report on the correlation of [68Ga]Ga-PSMA uptake with histological PSMA expression and on our preliminary experience with [177Lu]Lu-PSMA RLT in relapsing HGG.MethodsPatients with relapsing HGG underwent [68Ga]Ga-PSMA PET/MRI to evaluate eligibility for an individualized treatment approach with [177Lu]Lu-PSMA. Standard uptake values (SUV) for tumor and liver and respective tumor-to-background ratios (compared to the liver) (TBR) on [68Ga]Ga-PSMA PET/MRI were assessed. Eligibility criteria for [177Lu]Lu-PSMA therapy were exhaustion of all standard treatment options available and TBRmax>1.0. In 11 samples, immunohistochemical PSMA expression was determined, quantified using the H-score and correlated with uptake on [68Ga]Ga-PSMA PET/MRI.ResultsWe included 20 patients with a median age of 53 years (IQR 42-57). The median SUV on [68Ga]Ga-PSMA PET/MRI was 4.5 (3.7-6.2) for SUVmax and 1.4 (1.1-1.7) for SUVmean. The respective TBR was maximum 0.6 (0.4-0.8) and mean 0.3 (0.2-0.4). High TBRmax correlated with increased endothelial PSMA expression [H-score of 65 (62.5-77.5)]. Three patients (15%) presented a TBRmax>1.0 and qualified for [177Lu]Lu-PSMA RLT. No treatment related toxicity was observed.ConclusionOnly a minority of patients with relapsing HGG qualified for [177Lu]Lu-PSMA RLT. Our data demonstrates that PSMA expression in the neo-vasculature corresponds to PSMA uptake on [68Ga]Ga-PSMA PET/MRI and might be used as a screening tool for patient selection. Future prospective studies need to focus the debate on TBRmax thresholds as inclusion criteria for PSMA RLT.

PET/CT and inflammatory mediators in systemic sclerosis-associated interstitial lung disease.

ABSTRACTObjective:To investigate the correlation of HRCT findings with pulmonary metabolic activity in the corresponding regions using 18F-FDG PET/CT and inflammatory markers in patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD). Methods:This was a cross-sectional study involving 23 adult patients with SSc-associated ILD without other connective tissue diseases. The study also involved 18F-FDG PET/CT, HRCT, determination of serum chemokine levels, clinical data, and pulmonary function testing. Results:In this cohort of patients with long-term disease (disease duration, 11.8 ± 8.7 years), a nonspecific interstitial pneumonia pattern was found in 19 (82.6%). Honeycombing areas had higher median standardized uptake values (1.95; p = 0.85). Serum levels of soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 10 were higher in SSc patients than in controls. Serum levels of CCL2-a marker of fibroblast activity-were correlated with pure ground-glass opacity (GGO) areas on HRCT scans (p = 0.007). 18F-FDG PET/CT showed significant metabolic activity for all HRCT patterns. The correlation between serum CCL2 levels and GGO on HRCT scans suggests a central role of fibroblasts in these areas, adding new information towards the understanding of the mechanisms surrounding cellular and molecular elements and their expression on HRCT scans in patients with SSc-associated ILD. Conclusions: 18F-FDG PET/CT appears to be unable to differentiate the intensity of metabolic activity across HRCT patterns in chronic SSc patients. The association between CCL2 and GGO might be related to fibroblast activity in these areas; however, upregulated CCL2 expression in the lung tissue of SSc patients should be investigated in order to gain a better understanding of this association.

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer.

The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.

18F-Fluorodeoksiglukoz positron emisyon tomografi/bilgisayarlı tomografi’de kahverengi yağ dokusu aktivitesi ve kanser durumunun korelasyonu

Aim: In this study, we aimed to compare brown adipose tissue (BAT) activity on 18F-Flourodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography(CT) in patients with and without active cancer. &#x0D; Material and Methods: Results of the patients who underwent 18F-FDG PET/CT between January 2014 and February 2018 in Nuclear Medicine Department were evaluated retrospectively. Age, gender, body mass index (BMI), serum levels of glucose, bilirubin, total cholesterol (T-chol), low-density lipoprotein (LDL) and triglyceride (TG) of the patients were noted from the hospital database. Mean outdoor temperature of the day during PET/CT imaging was searched from National Weather Service archives. Diagnosis and disease activity status on PET/CT imaging were evaluated retrospectively. Standardized uptake value (SUV) and brown adipose tissue volume (BAV) were calculated on PET/CT images. Additionally, hepatic attenuation index and subcutaneous adipose tissue thickness (SCATT) were calculated from CT images. Difference between median SUV and BAV among groups with and without active cancer was analyzed. &#x0D; Results: Totally 78 (54 F; 24 M; mean age 34.415.6) patients who underwent 18F-FDG PET/CT for different oncological indications were included in the analysis. All the patients had different degrees of BAT uptake on PET/CT images. Median (min-max) values for SUV, BAV and SCATT were found as 8.0 (2.7-37.0), 26.9 (2.1- 116.0) cm3 and 15.0 (3.0- 46.0) mm, respectively. Hepatic attenuation index was 0-5%, 6-30% and &gt;30% in 56 (71%), 20 (26%) and 2 (3%) patients, respectively. Active disease was observed in 26 (33%) patients during PET/CT imaging. In the evaluation of the distribution of the adipose tissue parameters, median SUV (p=0.008) and BAV (p=0.008) of groups with and without active cancer were found statistically significant. &#x0D; Conclusion: BAT activity in patients with active cancer seems to be higher than that in patients without active disease, supporting the possible role of adipose tissue activation on cancer development and progression.

Efficacy of myocardial washout of 99mTc-MIBI/Tetrofosmin for the evaluation of inflammation in patients with cardiac sarcoidosis: comparison with 18F-fluorodeoxyglucose positron emission tomography findings.

Both myocardial perfusion scintigraphy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) are useful for the diagnosis of cardiac sarcoidosis (CS). However, the association between the washout of 99mTc-labeled tracer and FDG PET has not been established. This study aimed to evaluate the association between the washout of 99mTc-labeled tracer and FDG PET findings in patients with CS. We retrospectively analyzed 64 patients (65.0 ± 11.2years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) with 99mTc-labeled tracer and FDG PET. The SPECT images were acquired at 15min (early images) and 3h (delayed images) after injection and scored visually using a 17-segment model with a 5-point scoring system. The washout score was defined as the difference between the early and delayed total defect scores. FDG positivity was considered as focal or focal on diffuse patterns on visual assessment, and FDG uptake was quantified by measuring the standardized uptake value (SUV) of each of the 17 segments. The washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p < 0.001). The washout of 99mTc-labeled tracer can be a useful marker for the evaluation of FDG PET findings in patients with CS.

Imaging Biomarkers to Predict Outcomes in Patients with Large B-Cell Lymphoma with a Day 28 Partial Response By PET/CT Imaging Following CAR-T Therapy

Imaging Biomarkers to Predict Outcomes in Patients with Large B-Cell Lymphoma with a Day 28 Partial Response By PET/CT Imaging Following CAR-T Therapy