Maximum SUV Research Articles

Iterative reconstruction incorporating background correction improves quantification of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm

BackgroundA confounding issue in [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) is the spill in contamination from the bone into the aneurysm. This study investigates and corrects for this spill in contamination using the background correction (BC) technique without the need to manually exclude the part of the AAA region close to the bone. MethodsSeventy-two (72) datasets of patients with AAA were reconstructed with the standard ordered subset expectation maximization (OSEM) algorithm incorporating point spread function (PSF) modelling. The spill in effect in the aneurysm was investigated using two target regions of interest (ROIs): one covering the entire aneurysm (AAA), and the other covering the aneurysm but excluding the part close to the bone (AAAexc). ROI analysis was performed by comparing the maximum SUV in the target ROI (SUVmax(T)), the corrected cSUVmax (SUVmax(T) − SUVmean(B)) and the target-to-blood ratio (TBR = SUVmax(T)/SUVmean(B)) with respect to the mean SUV in the right atrium region. ResultsThere is a statistically significant higher [18F]-NaF uptake in the aneurysm than normal aorta and this is not correlated with the aneurysm size. There is also a significant difference in aneurysm uptake for OSEM and OSEM + PSF (but not OSEM + PSF + BC) when quantifying with AAA and AAAexc due to the spill in from the bone. This spill in effect depends on proximity of the aneurysms to the bone as close aneurysms suffer more from spill in than farther ones. ConclusionThe background correction (OSEM + PSF + BC) technique provided more robust AAA quantitative assessments regardless of the AAA ROI delineation method, and thus it can be considered as an effective spill in correction method for [18F]-NaF AAA studies.

Design, Synthesis, and Evaluation of Thienodiazepine Derivatives as Positron Emission Tomography Imaging Probes for Bromodomain and Extra-Terminal Domain Family Proteins.

To better understand the role of bromodomain and extra-terminal domain (BET) proteins in epigenetic mechanisms, we developed a series of thienodiazepine-based derivatives and identified two compounds, 3a and 6a, as potent BET inhibitors. Further in vivo pharmacokinetic studies and analysis of in vitro metabolic stability of 6a revealed excellent brain penetration and reasonable metabolic stability. Compounds 3a and 6a were radiolabeled with fluorine-18 in two steps and utilized in positron emission tomography (PET) imaging studies in mice. Preliminary PET imaging results demonstrated that [18F]3a and [18F]6a have good brain uptake (with maximum SUV = 1.7 and 2, respectively) and binding specificity in mice brains. These results show that [18F]6a is a potential PET radiotracer that could be applied to imaging BET proteins in the brain. Further optimization and improvement of the metabolic stability of [18F]6a are still needed in order to create optimal PET imaging probes of BET family members.

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients.

Simple SummaryMelanoma has become the most rapidly increasing cancer in Caucasian populations, causing 90% of skin cancer mortality. FDG-PET/CT has been recommended by the European 2019 guidelines for melanoma for staging and treatment response assessment in advanced melanoma highlighting the need for new outcome predictive biomarkers. In the context of melanoma, the evidence on the predictive value of semiquantitative parameters derived from FDG-PET/CT is still very limited. We here provide evidence, in a large cohort of metastatic melanoma patients, that FDG-PET/CT can be used to predict the early response to immune checkpoint inhibition. On a patient-basis, total tumor volume and semiquantitative parameters, such as total metabolic tumor volume MTV and total lesion glycolysis TLG of all metastases three months after treatment start are promising predictive biomarkers for the outcome in metastatic melanoma patients. Also, early complete response on a metastasis- and patient-level seems to be predictive for lasting complete response.We aimed to investigate, whether 18F-2-fluoro-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans performed at baseline (time point 0; TP 0) and three months after initiation of immunotherapy (time point 1; TP 1) can be used on a metastasis- and patient-level to predict the response to immune-checkpoint inhibition using FDG-PET/CT six months after treatment start (time point 2; TP 2) in metastatic melanoma patients. This single-center retrospective study considered metastatic melanoma patients treated with immune checkpoint inhibition from TP 0 to TP 2. An analysis on a metastasis- and patient-level was carried out. Tumor volume, standardized uptake values SUV (mean, maximum, and peak), metabolic tumor volume MTV and total lesion glycolysis TLG of each included metastasis were recorded at each time point, respectively TP 0, TP 1 and TP 2. Total tumor volume, total metabolic tumor volume and total lesion glycolysis per patient were also calculated at TP 0, TP 1 and TP 2. Treatment response was assessed at metastasis- and patient-level based on FDG-PET/CT scans at TP 2. 612 melanoma metastases in 111 patients were included. The analysis on a metastasis-level showed that metastatic SUVpeak at TP 1 and volume variation between TP 0 and TP 1 were the strongest negative predictive biomarkers for response. However, at TP 0, metastatic SUVmean and SUVpeak indicated a low negative prediction power, whereas initial metastatic volume was not a predictive biomarker. Also, melanoma metastases located in bone structures had a negative influence on the outcome at TP 2, particularly in women. The analysis on a patient-level showed, that total tumor volume, total metastatic tumor volume and total lesion glycolysis of all metastases three months after treatment initiation were strong negative predictive biomarkers for response to immunotherapy six months after initiation. Age and female sex were also found to be negative predictive biomarkers with lower predictive power. Interestingly, total tumor volume at TP 0 and number of metastases at TP 0 as well as the occurrence of early immune-related adverse events between TP 0 and TP 2 did not have any predictive value for early treatment response. FDG-PET/CT performed for treatment response assessment three months after initiation of immune checkpoint inhibition in metastatic melanoma patients can also be used to predict early response to treatment. On a metastasis-level SUV peak and volume variation of metastases are strong outcome predictive biomarkers. On a patient-level total tumor volume and semiquantitative parameters such as total metabolic tumor volume MTV and total lesion glycolysis TLG of all metastases are promising outcome predictive biomarkers. Also, early complete response on a metastasis- and patient-level seems to be predictive for lasting complete response.

AÂ New Dynamic PET-Based Scoring System Improves Outcome Prediction in Patients with Diffuse Large B-Cell Lymphoma

Introduction:The PETAL trial is a multicenter randomized controlled study for patients with aggressive lymphomas of diverse histologies (EudraCT 2006-001641-33, NCT00554164). In patients with diffuse large B-cell lymphoma (DLBCL) interim PET (iPET) reliably predicted progression-free survival (PFS) and overall survival (OS). Interim PET-based treatment changes had no impact on outcome (ASH 2014, abstract 391; ASH 2016, abstract 1857). To further improve outcome prediction we developed a new dynamic scoring system combining baseline total metabolic tumor volume (TMTV) with age and early iPET response.Methods:TMTV was measured in 510 patients with newly diagnosed DLBCL participating in the PETAL trial. Patients aged 18 to 80 years with a positive baseline PET received 2 cycles of rituximab (R), cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) followed by iPET and randomisation. In total, patients received 6 or 8 cycles of standard R-CHOP or 2 cycles of R-CHOP followed by 6 cycles of an intensive protocol originally designed for the treatment of Burkitt's lymphoma. A favorable iPET was defined as a reduction of the maximum SUV by > 66% compared to baseline. By using the 41% maximum standardized uptake value (SUV41max) thresholding method, baseline TMTV was calculated. Cut-off values were determined by receiver operating characteristic (ROC) analysis. The Youden index was used to compute the optimal cut-off point. Kaplan-Meier survival analysis was performed to estimate PFS and OS. By using uni- and multivariate cox-regression prognostic factors were analyzed.Results:Median follow-up was 4.4 years. The optimal cut-off for baseline TMTV was identified to be 313 cm3 with 310 patients (60.8%) belonging to the low TMTV group (range, 0.91-306.24 cm3) and 200 patients (39.2 %) belonging to the high TMTV group (319.71-8895.88cm3). A low baseline TMTV (< 313 cm3) was associated with a significantly better 5-year PFS (77.1% vs. 50.2%, p < 0.0001) and 5-year OS (84.1% vs. 64.3%, p < 0.0001). By creating a new prognostic score based on age (> 60 years =1 point), baseline TMTV (≥ 313 cm3 =1 point) and early iPET response (unfavorable =1 point) we identified four different risk groups: low (0 points) with a 5-year PFS of 84.6% (95% confidence interval [CI] 74.5% - 90.9%) and a 5-year OS of 91.9% (CI 82.3% - 96.4%), intermediate (1 point) with a 5-year PFS of 68.5% (CI 61.3% - 74.6%, p = 0.0003, hazard ratio [HR] 2.78) and a 5-year OS of 79.8% (CI 73.5%-84.8%, p = 0.0054, HR 2.78), high (2 points) with a 5-year PFS of 46.8% (CI 36.5%-56.5%, p < 0.0001, HR 6.31) and a 5-year OS of 56.7% (CI 45.9%-66.2%, p < 0.0001, HR 8.15) and very high (3 points) with a 5-year PFS of 18.3% (CI 3.7%-41.8%, p < 0.0001, HR 14.91) and a 5-year OS of 23.3% (CI 6.2%-46.7%, p < 0.0001, HR 18.75).Conclusion:Baseline TMTV is highly predictive for outcome in patients with DLBCL. By combining baseline TMTV with age and early iPET response we developed a new and easy to apply PET-based scoring system that detects patients at high and very high risk of disease progression and early death. Compared to the International Prognostic Index [IPI] and the enhanced NCCN-IPI the new score provided much better separation of curves. [Display omitted] DisclosuresHüttmann:Bristol-Myers Squibb, Takeda, Celgene, Roche: Honoraria; Gilead, Amgen: Other: Travel cost.

FDG-PET/CT response and outcome of neoadjuvant immunotherapy for clinical stage III melanoma.

e21569 Background: Neoadjuvant immunotherapy with nivolumab 3mg/kg and ipilimumab 1mg/kg for two cycles(N3+I1) or anti-PD1 for 3-8 weeks for clinical stage III melanoma have shown rates of pCR/near-pCR about 60% or 30%, respectively. The prognosis of this group seems to be excellent so far. On the other hand, patients classified as pathological non-response have a worse outcome and early identification of this group may allow us to tailor treatment before surgery. Methods: We conducted a retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant immune checkpoint blockade who did baseline and pre-operative FDG-PET/CT. The total number of FGD avid lesions and the percentual difference between the maximum SUV per lesion was calculated. The pathological results were correlated to FGD-PET/CT findings. Results: Between January 2019 and January 2021, nine patients with clinical stage III melanoma were identified. Six patients received Nivolumab 3m/kg and Ipilimumab 1mg/kg for two cycles and 3 received anti-PD1 for 60 days. Baseline FDG-PET/CT showed just one avid lesion in 7 patients, 2 avid lesions in one patient and 3 avid lesions in one patient. All known lesions identified by CT scan were also captured by FGD-PET/CT. After the neoadjuvant treatment, 4 patients achieved pCR/near-pCR. All of them were treated with N3+I1. Two of them had metabolic complete response (including the one with 3 PET- avid lesions) and 2 had reduction on FDG concentration (-31% and – 76%). Three patients had absence of response: 100% of viable tumor cells (VTC), all of them with increase in FDG concentration (+12% to + 307%) and appearance of a new lesion in one case. Two out of them were treated with anti-PD1. One patient had partial response (40% of VTC). Interestingly, this patient developed sarcoidosis-like reaction with increase of SUV in the index lesion (+68%) and appearance of mediastinal lymph-nodes. One patient, who had two lesions, presented a mixed response: complete response in one and 90% of VTC in the other. FDG-PET/CT was able to detect both responses (metabolic complete response and increase of FGD concentration of 17%, respectively). Conclusions: Reduction in FGD-PET/CT concentration with no appearance of new lesion(s) is associated with significant pathological response. An increase of SUV or appearance of new lesion(s) should be carefully interpreted.

Title: Case of Hyperthyroidism in a Patient on Anti-PD-1 (Programmed Cell Death Receptor-1 Blocking Antibody) Therapy Caused by Destructive Thyroiditis Followed by Graves’ Disease

Introduction: Immune checkpoint inhibitor (ICI) related thyroid dysfunction such as destructive thyroiditis and hypothyroidism can occur with Anti-PD-1 therapy. Graves’ disease (GD) however is considered rare. We report a case of isolated hyperthyroidism in a patient on Pembrolizumab, Anti-PD-1 presenting initially as destructive thyroiditis and later transitioned to GD. Case: 57 y.o lady was diagnosed with squamous cell carcinoma of cervix, stage 4 in 2016. She was noted to have asymptomatic goiter in 1997. PET scan in 02/2017 showed hypermetabolic activity in the right lobe nodule of 5.6 cm with maximum SUV of 9.8. Baseline TSH was in normal range in 04/2017. US guided fine needle biopsy of the nodule resulted as follicular neoplasm with 15-30%, risk of malignancy. Molecular test showed 40% risk of malignancy. Lobectomy was deferred. Pembrolizumab was initiated for advanced cervical cancer in 07/2018. Repeat PET in 10/2018 showed resolution of metastasis and right thyroid mass was stable. TSH remained in euthyroid range for 4 months until 11/ 2018. In 01/2019, her TSH was low and became undetectable in 03/2019 with high free T4 and total T3. She developed symptoms of hyperthyroidism. TSI was positive and TSHR Ab was negative. RAIU was low. No iodinated contrast study done prior to I123 scan. In 05/2019 to 08/2019, free T4 and total T3 was normal range with detectable but low TSH consistent with transient resolving thyroiditis. In 10/2019, thyroid hormones significantly increased with recurrence of hyperthyroidism. Both TSI and TSHR Ab were elevated confirming diagnosis of GD. Due to overt thyrotoxicosis, Methimazole (MMI) was initiated in 10/2019. She was briefly lost to follow up and stopped MMI. RAIU scan in 12 /2019 showed increased uptake consistent with GD. MMI was resumed in 04/2020. 06/2020 - 09/2020, MMI dose was titrated to achieve euthyroid state. In 09/25/2020, hypothyroidism was noted which improved with MMI dose reduction. Anti- TPO and Anti-Tg were negative. Pembrolizumab was stopped in 07/2020 due to dilated cardiomyopathy. She completed 2-year course of Pembrolizumab with advanced cervical cancer showing excellent response. Discussion: Observed thyroid dysfunction with ICI, is transient destructive thyroiditis followed by hypothyroidism, which can be permanent. Our patient had an initial low RAIU indicating destructive thyroiditis along with, mildly elevated TSI suggestive of superimposed autoimmune process. The elevated TSI predisposed to later occurrence of GD likely precipitated by Pembrolizumab. MMI provided therapeutic benefit. Conclusion: Less than 10 cases of GD with ICI and 5 cases of GD with Anti-PD- 1 have been reported. Our patient is a second case of persistent hyperthyroidism due to GD induced by Pembrolizumab. GD should be considered if hyperthyroidism persists or recurs in patients on ICI with destructive thyroiditis, which is mostly transient.

Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience.

The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Marcadores tumorales y 18 F-FDG PET/TC después de orquiectomía en seminoma: ¿hay alguna correlación?

ObjectiveThe aim of our study was to analyze the potential relationship between tumor markers and 18F-fluorodoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) results in patients affected by seminoma. Material and methods65 18F-FDG PET/CT scans of 41 patients with diagnosis of seminoma were analyzed and compared to alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). PET/CT studies were analyzed qualitatively and measuring the maximum and mean standardized uptake value body weight max (SUVbwmax, SUVbwmean), maximum SUV lean body mass (SUVlbm), maximum SUV body surface area (SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of hypermetabolic lesions. All values were compared with serum markers. Results31 PET/CT studies were true negative, 28 true positive, 6 false positive and 0 false negative with sensitivity of 100%, specificity of 84%, negative predictive value of 100%, positive predictive value of 82% and accuracy of 91%. No correlation between PET results and tumor marker levels was found and also between AFP and PET/CT semiquantitive parameters. All semiquantitative PET parameters were significantly related to hCG level. Conclusions18F-FDG PET/CT has good accuracy in evaluating patients with relapsed seminoma. hCG levels were significantly correlated with metabolic PET/CT parameters.

Assessment of quantitative [18F]Sodium fluoride PET measures of knee subchondral bone perfusion and mineralization in osteoarthritic and healthy subjects

Molecular information derived from dynamic [18F]sodium fluoride ([18F]NaF) PET imaging holds promise as a quantitative marker of bone metabolism. The objective of this work was to evaluate physiological mechanisms of [18F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA). Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K1), tracer extraction fraction, and total tracer uptake into bone (Ki) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings. Mean and maximum SUV and kinetic parameters Ki, K1, and extraction fraction were significantly different between Healthy subjects and subjects with OA. Between-group differences in metabolic parameters were observed both in regions where the OA group had degenerative changes as well as in regions that appeared structurally normal. Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [18F]NaF uptake in subchondral bone show potential to quantitatively evaluate the role of bone physiology in OA initiation and progression. Objective measures of bone metabolism from [18F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.

Improved prediction of chemoresistance in patients with diffuse large B-cell lymphoma through a new interim positron emission tomography-computed tomography evaluation model

Objectives The positron emission tomography (PET) could predict the prognosis of DLBCL patients, but the exact procedure on interim PET (iPET) to determine chemoresistant patients remains elusive. Methods We retrospectively analyzed 593 newly diagnosed DLBCL patients uniformly treated with R-CHOP regimen. Among them, 352 patients diagnosed from August 2010 to December 2016 were included in the test cohort and 241 patients diagnosed from January 2017 to December 2019 were included in the validation cohort. The iPET was evaluated with Deauville criteria and ΔSUVmax method. The reduction of maximal SUV between baseline and after 4 cycles of chemotherapy were defined as ΔSUVmax. The survival functions were depicted using the Kaplan–Meier method and compared with the log-rank test. Results Patients with iPET Deauville 4 had heterogeneous outcome and end of treatment complete response rates (eCRR). Combined Deauville with ΔSUVmax method, we proposed a modified-Deauville model: patients with Deauville 4 and ΔSUVmax > 70%, as well as those with Deauville 1–3, were reclassified into the modified-Deauville negative group, while patients with Deauville 4 and ΔSUVmax ≤ 70%, as well as those with Deauville 5, into the modified-Deauville positive group. In the test cohort, 3-year PFS, OS and eCRR of modified-Deauville negative group were 80.2%, 89.9% and 91.8%, significantly higher than those of positive group (12.5%, 27.3% and 29.2%, p ≤ .001). Similar results were found in the validation cohort, that 3-year PFS, OS and eCRR were 87.8%, 95.4%, 96.3% in modified-Deauville negative group, and 27.4%, 32.5%, 13.5% in positive group. Through modified-Deauville model, patients in iPET positive group had very low eCRR and were resistant to conventional chemotherapy. Conclusions The modified-Deauville model could better distinguish DLBCL patients with poor response to chemotherapy. Accordingly, these patients could be recognized early and provided with alternative therapeutic agents, which might improve the clinical outcome of refractory DLBCL patients.

An Intravenous 100-mL Lipid Emulsion Infusion Dramatically Improves Myocardial Glucose Metabolism Extinction in Cardiac FDG PET Clinical Practice.

Physiological myocardial accumulation of FDG impairs the diagnosis of inflammatory/infectious or tumoral myocardial detection by FDG PET/CT. We prospectively evaluated the addition, 3 hours before imaging, of an intravenous 100-mL lipid emulsion infusion (Intralipid) to a high-fat, low-carbohydrate diet (HFLCD) for at least 2 meals followed by a fast of at least 6 to 12 hours in patients referred for the diagnosis of myocardial inflammation, endocarditis, cardiac or paracardiac masses, intracardiac device, or prosthetic valve infections. Data of 58 patients consecutively included (28 Intralipid patients, 30 controls with HFLCD alone) were compared. FDG uptake in normal myocardium was scored from 0 (complete myocardial suppression) to 3 (high diffuse uptake). Myocardial maximal, peak, and mean SUV and the rate of interpretable images according to the clinical indication were measured. Compared with controls, Intralipid infusion significantly improved the rate of score 0 (89% vs 63%, P = 0.021), of interpretable images according to the clinical indication (100% vs 72%, P = 0.0047) and decreased all myocardial SUV values (eg, SUVmax median, 1.9 [interquartile range, 1.7-2.5] vs 3.1 [interquartile range, 2.3-4.1]; P < 0.001). A lipid emulsion infusion in addition to HFLCD better suppresses cardiac glucose metabolism than HFLCD alone.

Sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma

We evaluate the safety of bendamustine as a bridge to stem cell transplantation (SCT) in patients with relapsed/refractory lymphoma and residual disease after salvage therapy. Thirty-four subjects without complete responses (CR) received bendamustine 200 mg/m2/day for 2 days followed 14 days later by SCT. Sixteen subjects in partial remission (PR) with maximal FDG-PET SUVs ≤8 prior to bendamustine received autologous SCT, while 13 with suboptimal responses were allografted. Five subjects did not proceed to transplant. No bendamustine toxicities precluded transplantation and no detrimental effect on engraftment or early treatment-related mortality (TRM) was attributable to bendamustine. At 1 year, 75% of auto-recipients and 31% of allo-recipients were alive with CR. Two subjects in the autologous arm developed therapy-related myeloid neoplasia (t-MN). In conclusion, a bendamustine bridge to SCT can be administered without early toxicity to patients with suboptimal responses to salvage chemotherapy. However this approach may increase the risk of t-MN. (NCT02059239). Supplemental data for this article is available online at here.

Relationship between 18F-FDG uptake and heat shock protein 90α expression in colorectal cancer.

We investigated whether heat shock protein 90α (HSP90α) expression is associated with fluorine-18-labeled fluoro-2-deoxy-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography/computed tomography (PET/CT) can be used to predict the status of HSP90α expression in colorectal cancer (CRC). The medical records and preoperative 18F-FDG PET/CT studies of 51 patients with newly diagnosed CRC who underwent surgical treatment were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor was calculated from the level of 18F-FDG uptake. HSP90α expression was determined by immunohistochemistry. The relationship between SUVmax and HSP90α expression was analyzed. Colorectal cancer with high HSP90α expression had significantly higher SUVmax than CRC with low HSP90α expression (18.88±10.06 vs. 12.38±5.04, P=0.003). There was a significant correlation between HSP90α expression and 18F-FDG uptake (r=0.354, P=0.011). The highest accuracy for determining HSP90α status (68.6%) was obtained with a SUVmax cut-off of 15.4. Maximum SUV was the only predictor of HSP90α expression on multivariate logistic regression analysis (Odds Ratio=5.384, P=0.016). The expression status of HSP90α was significantly related to 18F-FDG uptake in CRC.

The impact of IV contrast enhanced 18F-FDG PET/CT on the staging of bladder cancer.

The aim of this retrospective study was to compare the diagnostic accuracies of conventional radiological imaging (CI) methods magnetic resonance imaging or computed tomography (MRI or CT) and intra venous (IV) contrast enhanced (CE) fluorine-18-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) for the staging of bladder cancer (BC). The 18F-FDG CE-PET/CT results of 35 consecutive patients with BC were analyzed. Diagnostic value of CE-PET/CT and CI are compared for their accuracy in revealing primary tumors, nodal-distant metastasis, and the final tumor staging. The imaging results were compared with the gold standard, including of histopathology and clinical follow-up. We also investigated the effect of maximum standardize uptake value (SUVmax) and lymph node metastasis on survival. The CE-PET/CT had a diagnostic accuracy of 89% (31/35), compared to 57% (19/35) for CI. The results of CE-PET/CT imaging lead to upstaging in 37% (13/35) patients compared to CI staging. For primary tumor detection, the sensitivity of CE-PET/CT was 97% (34/35). Contrast enhanced-PET/CT detected nodal metastases in 19 (54%) patients, whereas CI detected in 9 (26%) patients. Contrast enhanced-PET/CT detected distant metastases in 14 (40%) patients, while conventional methods showed distant metastases in 9 (26%) patients. Maximum SUV of primary tumor does not have a significant effect on survival, whereas the median survival time of patients without lymph node metastasis is longer than patients who have lymph node metastasis (P=0.038). These data suggest that 18F-FDG CE-PET/CT had good diagnostic performance compared to conventional imaging for detecting primary tumor, nodal and distant metastasis in BC. Upstaging by CE-PET/CT changed the management of patients.

Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A.

Synaptic abnormalities are associated with many brain disorders. Recently, we developed a novel synaptic vesicle glycoprotein 2A (SV2A) radiotracer [18F]SynVesT-1 and demonstrated its excellent imaging and binding properties in nonhuman primates. The aim of this study was to perform dosimetry calculations in nonhuman primates and to evaluate this tracer in humans and assess its test-retest reliability in comparison with [11C]UCB-J. Three rhesus monkeys underwent whole body dynamic PET scanning to estimate the absorbed dose. PET scans in six healthy human subjects were acquired. Time-activity curves (TACs) were generated with defined regions of interest (ROI). Reproducibility of distribution volume (VT) values and its sensitivity to scan duration were assessed with the one-tissue compartment (1TC) model. Non-displaceable binding potential (BPND) was calculated using centrum semiovale as the reference region. The dosimetry study showed high uptake in the urinary bladder and brain. In humans, [18F]SynVesT-1 displayed high uptake with maximum SUV of ~10 and appropriate kinetics with a quick rise in tracer uptake followed by a gradual clearance. Mean 1TC VT values (mL/cm3) ranged from 3.4 (centrum semiovale) to 19.6 (putamen) and were similar to those of [11C]UCB-J. Regional BPND values were 2.7-4.7 in gray matter areas, and mean BPND values across all ROIs were ~ 21% higher than those of [11C]UCB-J. The absolute test-retest variability of VT and BPND was excellent (< 9%) across all brain regions. [18F]SynVesT-1 demonstrates outstanding characteristics in humans: fast and high brain uptake, appropriate tissue kinetics, high levels of specific binding, and excellent test-retest reproducibility of binding parameters. As such, [18F]SynVesT-1 is proved to be a favorable radiotracer for SV2A imaging and quantification in humans.

Associations of physiologic myocardial 18F-FDG uptake with fasting duration, HbA1c, and regular exercise.

The variability of physiologic 18F-FDG uptake in the myocardium has hampered the accurate evaluation of cardiac glucose metabolism. We investigated the effects of multiple factors, including fasting duration and physical activity, on the physiologic uptake of 18F-FDG by the myocardium in healthy participants. A total of 446 participants (predominantly male, 91%) in a health screening program were included in this retrospective study. For the visual analysis of myocardial 18F-FDG uptake, the participants were categorized into three groups according to qualitative visual scales (QVS). For the quantitative analysis, the maximum SUV of the left ventricular myocardium was measured. Significant differences were observed in fasting duration (p < 0.001), SUVmax (p < 0.001), aspartate aminotransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), gamma-glutamyl transpeptidase (γ-GTP) (p = 0.001), and uric acid (p = 0.015) among the QVS groups. Participants who regularly exercised with vigorous activity (p = 0.032) and HbA1c > 6% (p = 0.005) showed significant association with myocardial FDG uptake in the Chi-squared test. The median value of fasting duration decreased significantly as the QVS of the myocardium increased. Twenty-nine of the 31 participants (93.5%) who fasted for 21.5h or more showed a suppressed FDG uptake (mean SUVmax = 2.1). In multivariate logistic regression analysis, fasting duration (OR = 0.74, 95% CI 0.69-0.80, p < 0.001), HbA1c > 6% (OR = 0.29, 95% CI: 0.12 - 0.66, p = 0.004), uric acid (OR = 0.82, 95% CI 0.68-1.00, p = 0.049) and regular exercise with vigorous activity (OR = 1.75, 95% CI 1.13-2.70, p = 0.012) were significant factors for physiologic myocardial FDG uptake. Reduced physiologic 18F-FDG uptake of the myocardium was associated with longer fasting duration, higher level of HbA1c, and less frequency of regular exercise with vigorous activity. For the preparation of cardiac 18F-FDG PET, inclusion of longer fasting duration (more than 18h) might be necessary for the adequate suppression of physiologic 18F-FDG myocardial uptake.

18F-FDG PET/CT Parameters for Predicting Prognosis in Esophageal Cancer Patients Treated With Concurrent Chemoradiotherapy.

Background and Aims:This study evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) performed before and after concurrent chemoradiotherapy (CCRT) in esophageal cancer.Methods:We analyzed the prognosis of 50 non-metastatic squamous cell esophageal cancer (T1-4N0-2) patients who underwent CCRT with curative intent at Inje University Busan Paik Hospital and Haeundae Paik Hospital from 2009 to 2019. Median total radiation dose was 54 Gy (range 34-66 Gy). Our aim was to investigate the relationship between PET/CT values and prognosis. The primary end point was progression-free survival (PFS).Results:The median follow-up period was 9.9 months (range 1.7-85.7). Median baseline maximum standard uptake value (SUVmax) was 14.2 (range 3.2-27.7). After treatment, 29 patients (58%) showed disease progression. The 3-year PFS and overall survival (OS) were 24.2% and 54.5%, respectively. PFS was significantly lower (P = 0.015) when SUVmax of initial PET/CT exceeded 10 (n = 22). However, OS did not reach a significant difference based on maximum SUV (P = 0.282). Small metabolic tumor volume (≤14.1) was related with good PFS (P = 0.002) and OS (P = 0.001). Small total lesion of glycolysis (≤107.3) also had a significant good prognostic effect on PFS (P = 0.009) and OS (P = 0.025). In a subgroup analysis of 18 patients with follow-up PET/CT, the patients with SUV max ≤3.5 in follow-up PET/CT showed longer PFS (P = 0.028) than those with a maximum SUV >3.5.Conclusion:Maximum SUV of PET/CT is useful in predicting prognosis of esophageal cancer patients treated with CCRT. Efforts to find more effective treatments for patients at high risk of progression are still warranted.

Prospective Correlation of Prognostic Immunohistochemical Markers With SUV and ADC Derived From Dedicated Hybrid Breast 18F-FDG PET/MRI in Women With Newly Diagnosed Breast Cancer.

The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI. Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used. A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001). The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy.

Tumor markers and 18F-FDG PET/CT after orchiectomy in seminoma: Is there any correlation?

ObjectiveThe aim of our study was to analyze the potential relationship between tumor markers and 18F-fluorodoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) results in patients affected by seminoma. Material and methods65 18F-FDG PET/CT scans of 41 patients with diagnosis of seminoma were analyzed and compared to alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). PET/CT studies were analyzed qualitatively and measuring the maximum and mean standardized uptake value body weight max (SUVbwmax, SUVbwmean), maximum SUV lean body mass (SUVlbm), maximum SUV body surface area (SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of hypermetabolic lesions. All values were compared with serum markers. Results31 PET/CT studies were true negative, 28 true positive, 6 false positive and 0 false negative with sensitivity of 100%, specificity of 84%, negative predictive value of 100%, positive predictive value of 82% and accuracy of 91%. No correlation between PET results and tumor marker levels was found and also between AFP and PET/CT semiquantitive parameters. All semiquantitative PET parameters were significantly related to hCG level. Conclusions18F-FDG PET/CT has good accuracy in evaluating patients with relapsed seminoma. HCG levels were significantly correlated with metabolic PET/CT parameters.

Local Review Versus (vs) Central Review of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in Diffuse Large B-Cell Lymphoma (DLBCL): Results from the CALGB 50303 Trial [Alliance

Local Review Versus (vs) Central Review of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in Diffuse Large B-Cell Lymphoma (DLBCL): Results from the CALGB 50303 Trial [Alliance