Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

PURPOSE: Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). MATERIALS AND METHODS: This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. RESULTS: Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4 h, 2.6 ± 1.0; 24 h, 2.2 ± 1.0; kidney: 4 h, 8.9 ± 1.8; 24 h, 7.0 ± 2.0; and spleen; 4 h, 11.3 ± 4.5; 24 h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4 h, p < 0.001; 24 h, p < 0.001) (4 h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24 h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). CONCLUSION: We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

Assessment of unilateral condylar hyperplasia with quantitative SPECT/CT.

Purpose: The current study aimedto assess condylar activityin patients with unilateral condylar hyperplasia (UCH) with quantitative SPECT/CT. Patients and methods: This retrospective study included patients with UCH who underwent quantitative SPECT/CT. SPECT analysis and quantification of SPECT/CT were performed, and the maximum count per pixel and SUVmax of either side of the condyles were calculated. Results: 39 patients were included in the analysisand classified into three subgroups according to the percentile differential right-left ratio: inactive group, left active (LA) group, and right active (RA) group. Totally, the SUVmax of the affected side is significantly higher than the unaffected side (active:5.93 ± 2.43 vs inactive:3.62 ± 1.76, P < 0.001), SUVmax-based ratios correlated well with the ratios based on maximum count (R = 0.944, P < 0.001). ROC analysis showed poorSUVmaxperformance in differentiation between theactive condyles and the inactive condyles due to the lower area under the curve (AUC) (0.588). In subgroup analysis, the affected side is significantly higher than the unaffected side in active groups with SUVmax, no significant difference was found between the active sides or the inactive sides of active groups. Interestingly, the SUVmax of the left side was statistically higher than that of the right sidein the inactive group (P = 0.01),while the left side of the right active group has significantlylower activitythan that in the inactive group, meanwhile,the right side showed no significant difference. Furthermore, each side showed no significant difference between the left active group and the inactive group. Conclusions: SUVmax is not an optimal measurement effectively used to evaluate active condyles. However, SUV ratios correlated well with the count ratios, and the left side of condyles showed a peculiar feature in condyle growth status reflected in radioactivity quantified with SPECT/CT, which needs further study to determine the role in the development of the UCH.

Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer.

PURPOSE: The study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC). MATERIALS AND METHODS: A total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters-standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)-to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction. RESULTS: Our study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression. CONCLUSION: The present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.

Synthetic PET via Domain Translation of 3-D MRI.

Historically, patient datasets have been used to develop and validate various reconstruction algorithms for PET/MRI and PET/CT. To enable such algorithm development, without the need for acquiring hundreds of patient exams, in this article we demonstrate a deep learning technique to generate synthetic but realistic whole-body PET sinograms from abundantly available whole-body MRI. Specifically, we use a dataset of 56 18F-FDG-PET/MRI exams to train a 3-D residual UNet to predict physiologic PET uptake from whole-body T1-weighted MRI. In training, we implemented a balanced loss function to generate realistic uptake across a large dynamic range and computed losses along tomographic lines of response to mimic the PET acquisition. The predicted PET images are forward projected to produce synthetic PET (sPET) time-of-flight (ToF) sinograms that can be used with vendor-provided PET reconstruction algorithms, including using CT-based attenuation correction (CTAC) and MR-based attenuation correction (MRAC). The resulting synthetic data recapitulates physiologic 18F-FDG uptake, e.g., high uptake localized to the brain and bladder, as well as uptake in liver, kidneys, heart, and muscle. To simulate abnormalities with high uptake, we also insert synthetic lesions. We demonstrate that this sPET data can be used interchangeably with real PET data for the PET quantification task of comparing CTAC and MRAC methods, achieving ≤ 7.6% error in mean-SUV compared to using real data. These results together show that the proposed sPET data pipeline can be reasonably used for development, evaluation, and validation of PET/MRI reconstruction methods.

Optimized 18F-FDG PET-CT Method to Improve Accuracy of Diagnosis of Metastatic Cancer.

The diagnosis of cancer by FDG PET-CT is often inaccurate owing to subjectivity of interpretation. We compared the accuracy of a novel normalized (standardized) method of interpretation with conventional non-normalized SUV. Patients (n = 393) with various malignancies were studied with FDG PET/CT to determine the presence or absence of cancer. Target lesions were assessed by two methods: (1) conventional SUVmax (conSUVmax) and (2) a novel method that combined multiple factors to optimize SUV (optSUVmax), including the patient's normal liver SUVmax, a liver constant (k) derived from a review of the literature, and use of site-specific thresholds for malignancy. The two methods were compared to pathology findings in 154 patients being evaluated for mediastinal and/or hilar lymph node (MHLNs) metastases, 143 evaluated for extra-thoracic lymph node (ETLNs) metastases, and 96 evaluated for liver metastases. OptSUVmax was superior to conSUVmax for all patient groups. For MHLNs, sensitivity was 83.8% vs. 80.7% and specificity 88.7% vs. 9.6%, respectively; for ETLNs, sensitivity was 92.1% vs. 77.8% and specificity 80.1% vs. 27.6%, respectively; and for lesions in the liver parenchyma, sensitivity was 96.1% vs. 82.3% and specificity 88.8% vs. 23.0%, respectively. Optimized SUVmax increased diagnostic accuracy of FDG PET-CT for cancer when compared with conventional SUVmax interpretation.

Are Semiquantitative Methods Superior to Deauville Scoring in the Monitoring Therapy Response for Pediatric Hodgkin Lymphoma?

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) and the PET ratio (rPET) versus the Deauville score (DS) for assessing the chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (aged 8-16 years) were enrolled at baseline, interim (after the second or third chemotherapy round) and post-therapy (on completion of first-line chemotherapy). Interim and post-therapy DS, ΔSUVmax% and rPET were compared as response predictors. Patients were classified as responders or non-responders based on a 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively, in predicting the therapy response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%, repsectively. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, respectively, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, respectively, with a 76.8% cutoff. Compared to ΔSUVmax%, DS showed a significantly higher sensitivity, specificity (p < 0.05) and NPV (p < 0.01). The sensitivity, specificity, PPV, NPV and accuracy of rPET in predicting the therapy response at 24 months were 76.1%, 100%, 100%, 35.3% and 78.8%, respectively, with a cut-off of 1.31. DS and rPET showed comparable predictive performance (p > 0.58). In conclusion, DS is an easier method with better performance than ΔSUVmax% and rPET in predicting the chemotherapy response in pediatric HL patients.

Utility of serum ketone levels for assessment of myocardial glucose suppression for 18F-fluorodeoxyglucose PET in patients referred for evaluation of endocarditis.

BACKGROUND: 18F-FDG PET/CT is used to diagnose cardiac sarcoidosis and endocarditis. It requires myocardial glucose utilization (MGU) suppression to avoid false positives, which occur in up to 20% of patients. Serum beta-hydroxybutyrate (BHB) levels may help identify incomplete suppression of MGU. We determined the optimal timing and diagnostic thresholds to identify incomplete suppression of MGU. METHODS AND RESULTS: We retrospectively identified 114 patients referred for 18F-FDG PET/CT for endocarditis, wherein myocardial uptake outside of paravalvular regions is not related to pathology and can be confidently ascribed as being due to inadequate suppression of MGU. Patients followed a high-fat, low-carbohydrate diet and received heparin. Serum BHB, insulin, glucose and hemoglobin A1c were measured. Maximum standardized uptake value (SUVmax) of left ventricle (LV) and mean SUV (SUVmean) in LV blood pool (LVBP) was measured. Logistic regression and area under the receiver-operating characteristic analyses were used to quantify the relationship between biomarkers and MGU suppression. A threshold of BHB ≥ 0.35 mmol·L-1 to detect suppression resulted in sensitivity of 88% and specificity of 61%. A threshold of BHB ≥ 0.95 mmol·L-1 resulted in sensitivity of 45% and specificity of 100%. AUC was 0.87. BHB measured ~ 4 hours prior to 18F-FDG injection performed similarly to or better than later timepoints. CONCLUSIONS: Serum BHB levels are useful for assessing suppression of MGU and could simplify interpretation of 18F-FDG PET/CT inflammation studies.

New quantitative indices of cardiac amyloidosis with 99mTc-pyrophosphate scintigraphy.

PURPOSE: Amyloid light chain (AL) and transthyretin (ATTR) are the major subtypes of cardiac amyloidosis (CA). 99mTc-pyrophosphate (PYP) scintigraphy is used to differentiate ATTR from other CA subtypes. We adapted the standardized uptake value (SUV) for 99mTc-PYP and proposed two quantitative indices, amyloid deposition volume (AmyDV) and total amyloid uptake (TAU). This study aimed to evaluate the utility of these quantitative indices in differentiating ATTR from non-ATTRs. MATERIALS AND METHODS: Before the SUV measurement, the Becquerel calibration factor (BCF) of 99mTc was obtained by a phantom experiment. Thirty-two patients who had undergone hybrid SPECT/CT imaging 3 h after injection of 99mTc-PYP (370 MBq) were studied. CT attenuation correction for image reconstruction was applied in all. We calculated SUV, AmyDV, and TAU using a quantitative analysis software program for bone SPECT (GI-BONE) and analyzed AmyDV using two methods: threshold method (set 40%); and constant value method (average SUVmax of ribs). We assessed the diagnostic ability of heart-to-contralateral lung (H/CL) ratio, SUV, AmyDV, and TAU to differentiate ATTR from non-ATTR using receiver operating characteristic (ROC) analysis. RESULTS: Statistically significant differences in all quantitative indices were observed between ATTR and non-ATTR. The area under the curve of each quantitative index for discriminating between ATTR and non-ATTR were as follows: H/CL, 0.997; SUVmax, 0.953; SUVmean (M1), 0.964; SUVmean (M2), 0.969; AmyDV (M1), 0.875; AmyDV (M2), 0.974; and TAU, 0.974. The AmyDV (M2) had higher diagnostic ability than AmyDV (M1). Thus, TAU was calculated as AmyDV (M2) × SUVmean (M2). In the ROC curve, SUV, AmyDV, and TAU had almost the same diagnostic ability as H/CL in distinguishing ATTR from non-ATTRs. CONCLUSIONS: We propose two novel 3D-based quantitative parameters (AmyDV and TAU) that have almost equal ability to discriminate ATTR from non-ATTR.

Correlation between 18-FDG standardized uptake value and tumor grade in patients with resectable non-small cell lung cancer.

Background: Positron-emission tomography (PET) is widely used for staging lung cancer. Although a correlation between the fluorodeoxyglucose standardized uptake value (SUV) and the histologic grade of the tumor has been shown in several studies, little is known about the impact of different clinical variables on this correlation. This study aimed to evaluate the correlation between tumor SUV and tumor grade in a large cohort of patients and to analyse the impact of clinical factors on this correlation. Methods: This retrospective cohort study including patients with non-small cell lung cancer age 18-90 years, with clinical stage I-IVA, who underwent curative-intent lung resection. Results: Data from 726 patients was included in this study. There was a strong correlation between SUV and primary tumor grade in the whole cohort (P<0.001), which was significant in both sexes (P<0.001) and in all selected age groups (P<0.001-0.03). There was a significant SUV-grade correlation for the right upper and left lower lobes, as well as for the central location in the right lung (P<0.001, P=0.005 and P=0.04, respectively). Moreover, a significant SUV-grade correlation was found for squamous cell cancer and adenocarcinoma (P<0.001 and P=0.01, respectively), and for T1-T3 factors (P<0.001, P=0.006, P=0.005 respectively). Conclusions: In patients with resectable lung cancer, a significant correlation was observed between the SUV of the primary tumor and its grade. This correlation was maintained for both sexes, age groups, most common histological types and T factors T1-T3.

Clinical significance of the combination of preoperative SUVmax and CEA in patients with clinical stage IA lung adenocarcinoma.

BACKGROUND: Preoperative maximum standardized uptake value (SUVmax) of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early-stage lung adenocarcinoma is not well known. METHODS: We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax <2.96 and CEA ≥5.3 or SUVmax ≥2.96 and CEA <5.3) and low SC group (SUVmax <2.96 and CEA <5.3). RESULTS: Kaplan-Meier curve analysis showed that patients with clinical stage IA lung adenocarcinoma in the high SC group had significantly shorter overall survival (OS) and recurrence-free survival (RFS) than the other groups (p = 0.011 and p < 0.0001, respectively). Multivariate analysis showed that high SC was an independent prognostic factor of OS (p = 0.029) and RFS (p < 0.0001). CONCLUSIONS: High values of SUVmax and CEA were associated with poor OS and RFS in patients with stage IA lung adenocarcinoma. Simultaneous evaluation of SUVmax and CEA may be an effective prognostic marker to determine the optimal treatment strategy of early-stage lung adenocarcinoma.

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization.

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis. Methods: Original analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Results: FDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer. Conclusion: FDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

Radiological Characteristics of Patients With Anti-MDA5-Antibody-Positive Dermatomyositis in 18F-FDG PET/CT: A Pilot Study.

Objective: To elucidate the 18F-fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in the patients with anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM). Methods: This retrospective cross-sectional study included 26 patients with anti-MDA5+ DM and 43 patients with anti-MDA5 negative (anti-MDA5-) idiopathic inflammatory myopathy (IIM) who were examined by 18F-FDG PET/CT from January 1, 2017 to December 31, 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of the patients were measured and analyzed. Results: Compared with the anti-MDA5- group, the patients in the anti-MDA5+ group showed higher bilateral lung SUVmax (p = 0.029), higher SUVmax of spleen (p = 0.011), and bone marrow (p = 0.048). Significant correlations between the spleen SUVmax and serum ferritin levels (r = 0.398, p < 0.001), erythrocyte sedimentation rate (ESR) (r = 0.274, p = 0.023), platelet count (r = -0.265, p= 0.028), myositis disease activity assessment score (r = 0.332, p = 0.005), bone marrow SUVmax (r = 0.564, p < 0.001), and bilateral lung SUVmax (r = 0.393, p < 0.001) were observed. Conclusion: 18F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in the patients with anti-MDA5+ DM.

[Improvement of Standardized Uptake Value Accuracy in the 99mTc Body SPECT and SPECT/CT: Optimization of the Phantom for Calculating Becquerel Calibration Factor and Correction Method].

PURPOSE: The purpose of this study was to evaluate the best phantom for calculating the becquerel calibration factor (BCF) and correction method to obtain the improvement of standardized uptake value (SUV) accuracy in both single photon emission computed tomography (SPECT) and SPECT/CT. METHOD: A SPECT/CT scanner was used in this study. BCFs were calculated using four phantoms with different cross sections including National Electrical Manufacturers Association International Electrotechnical Commission body phantom (NEMA IEC body phantom) filled with 99mTcO4-, and five correction methods were used for reconstruction. SUVs were calculated by the NEMA IEC body phantom and pediatric phantom in house with these BCFs. We then measured SUVmean in the background region of the NEMA IEC body phantom, SUVmax and SUVpeak of the 37-mm-diameter sphere. RESULTS: In the SPECT scanner, SUVmean and SUVmax measured 1.04 and 4.02, respectively, in the case of BCF calculation and SUV measurement using NEMA IEC body phantoms without corrections. In the SPECT/CT scanner, SUVmean with CT attenuation correction (AC) was in agreement with the theoretical values using each phantom. SUVmax showed the same trend. CONCLUSION: In the SPECT scanner, it is possible to obtain a highly accurate SUV by using a phantom that matches the size of the subject for BCF calculation and without correction. In the SPECT/CT scanner, highly accurate SUVs can be obtained by using CT-based attenuation correction, and these values do not depend on the size of the BCF calculation phantom.

Test-retest repeatability of quantitative bone SPECT/CT.

OBJECTIVE: Technological innovations in single-photon emission computed tomography (SPECT) have enabled a more accurate quantitative evaluation of the uptake, and the standardized uptake value (SUV) can be measured as a semi-quantitative value, as in positron emission tomography. Nevertheless, the reliability of the SUV of bone SPECT has not been well established. The purpose of this study is to evaluate the test-retest repeatability of the SUV of bone SPECT/CT in clinical settings. METHODS: This prospective study recruited patients with prostate cancer planning to receive bone SPECT/CT for the evaluation of bone abnormality between August 2017 and September 2019. Bone images were acquired twice by an integrated SPECT/CT scanner (Symbia Intevo, Siemens) within a 4- to 10-day interval. The maximum SUV (SUVmax) and peak SUV (SUVpeak) were calculated for the volumes of interests on the normal bone areas, degeneration/fracture lesions, and metastatic lesions. To determine repeatability, we calculated statistical indicators, including intraclass correlation coefficient (ICC), repeatability coefficient (RC), and mean absolute percentage difference (MAPD). For the ICC, the 95% confidential interval (CI) was also calculated, and an ICC of ≥ 0.8 was defined as an almost perfect correlation. RESULTS: Twelve male patients were enrolled in the study (58-86 years; median, 71 years), and a total of 229 volumes of the interest were included in the analyses. The ICCs were 0.968 [95% CI (0.959, 0.975)] for SUVmax and 0.976 [95% CI (0.969, 0.981)] for SUVpeak. The RCs of the relative difference were 30.7% for SUVmax and 27.6% for SUVpeak, and the MAPDs (± standardized deviation) of all lesions were 12.3 ± 9.9% for SUVmax and 11.5 ± 8.3% for SUVpeak. The RCs and the MAPDs showed comparable value with the previous report regarding repeatability studies on PET. CONCLUSION: An almost perfect correlation was demonstrated by repeated SUVmax and SUVpeak measured by quantitative integrated SPECT/CT. The quantitative values could be reliable indicators in patient management.

Age-related changes of standardized uptake values in the blood pool and liver: a decade-long retrospective study of the outcomes of 2,526 subjects.

BACKGROUND: Background activity on fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is often used as a reference to assess a patient's response to tumor treatment. To produce a suitable background activity reference, we examined the variations in standardized uptake values (SUVs) in the blood pool and liver of a large multi-aged population. METHODS: A total of 2,526 subjects underwent 18F-FDG PET/CT examinations and were divided into 12 age groups. Pearson's partial correlation and multivariate regression analyses were performed to assess the associations between individual factors and SUVs of the blood pool and liver and to identify the factor that most influenced the SUVs. The mean SUVs across the age groups were also determined. RESULTS: Positive correlations were found between individual factors and SUVs. Age appeared to be the most important predictor of SUVs and was significantly associated with the blood pool SUVmax (ß=0.466, P=0.000), blood pool SUVmean (ß=0.393, P=0.000), liver SUVmax (ß=0.347, P=0.000), and liver SUVmean (ß=0.354, P=0.000). Blood pool and liver SUVs rose rapidly until the age of 20 and then showed a slow upward trend without reaching a plateau. CONCLUSIONS: Age is an important factor that influences variations in the blood pool and liver SUVs. Our study clarified this understanding of age-related variations in SUVs and provided a normal range of blood pool and liver SUVs that may aid clinicians in evaluating tumors with greater accuracy.

Intensity threshold based solid tumour segmentation method for Positron Emission Tomography (PET) images: A review.

Accurate, robust and reproducible delineation of tumour in Positron Emission Tomography (PET) is essential for diagnosis, treatment planning and response assessment. Since standardized uptake value (SUV) - a normalized semiquantitative parameter used in PET is represented by the intensity of the PET images and related to the radiotracer uptake, a SUV based threshold method is a natural choice to delineate the tumour. However, determination of an optimum threshold value is a challenging task due to low spatial resolution, and signal-to-noise ratio (SNR) along with finite image sampling constraint. The aim of the review is to summarize different fixed and adaptive threshold-based PET image segmentation approaches under a common mathematical framework Advantages and disadvantages of different threshold based methods are also highlighted from the perspectives of diagnosis, treatment planning and response assessment. Several fixed threshold values (30%-70% of the maximum SUV of the tumour (SUVmaxT)) have been investigated. It has been reported that the fixed threshold-based method is very much dependent on the SNR, tumour to background ratio (TBR) and the size of the tumour. Adaptive threshold-based method, an alternative to fixed threshold, can minimize these dependencies by accounting for tumour to background ratio (TBR) and tumour size. However, the parameters for the adaptive methods need to be calibrated for each PET camera system (e.g., scanner geometry, image acquisition protocol, reconstruction algorithm etc.) and it is not straight forward to implement the same procedure to other PET systems to obtain similar results. It has been reported that the performance of the adaptive methods is also not optimum for smaller volumes with lower TBR and SNR. Statistical analysis carried out on the NEMA thorax phantom images also indicates that regions segmented by the fixed threshold method are significantly different for all cases. On the other hand, the adaptive method provides significantly different segmented regions only for low TBR with different SNR. From this viewpoint, a robust threshold based segmentation method that will be less sensitive to SUV maxT , SNR, TBR and volume needs to be developed. It was really challenging to compare the performance of different threshold-based methods because the performance of each method was tested on dissimilar data set with different data acquisition and reconstruction protocols along with different TBR, SNR and volumes. To avoid such difficulties, it will be desirable to have a common database of clinical PET images acquired with different image acquisition protocols and different PET cameras to compare the performance of automatic segmentation methods. It is also suggested to report the changes in SNR and TBR while reporting the response using threshold based methods.

Utility of [18F] Fluoro-Deoxyglucose Positron Emission Tomography/Computed Tomography for Staging and Therapy Response Evaluation in Pediatric Rhabdomyosarcoma: A Case Series and Literature Review.

Background: The role of [18F] fluoro-deoxyglucose [[18F] FDG] positron emission tomography (PET)/computed tomography (CT) in pediatric rhabdomyosarcoma (RMS) is not well-established. This manuscript explores the role of staging and therapy response evaluation of PET/CT in a series of patients with RMS. Methods: Thirteen consecutive patients with pathologically proven RMS underwent baseline PET/CT scan and a second PET/CT for evaluation of therapy response. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), highest standardized uptake peak value (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from baseline PET/CT and were used as potential predictors for evaluation of metabolic treatment response. Results: On baseline PET/CT, most RMSs are located in the pelvic cavity, and upper arms ranked second. The primary lesions were large and showed invasion to the surrounding tissues. Lymph node metastases were seen in eight patients, and eight patients showed distant metastasis to the lung, liver, and bone. The median SUVmax, SUVmean, and SUVpeak of primary sites were 7.1, 4.0, and 5.9, respectively. The median MTV and TLG were 196.6 cm3 and 780.2, respectively. After therapy, six patients received complete metabolic response (CMR) and non-CMR occurred in seven patients on the second PET/CT. SUVmax, SUVpeak, MTV, and TLG in patients with CMR were significantly lower than those in patients with non-CMR. Conclusions: Primary sites and metastatic lesions of RMS demonstrate increased glycolytic activity, which may allow them to be imaged using [18F] FDG PET/CT. Metabolic parameters derived from the baseline PET/CT have potential value for predicting CMR to therapy in pediatric RMS.

Prognostic value of lymph node to primary tumor standardized uptake value ratio in unresectable esophageal cancer.

BACKGROUND: Unresectable esophageal cancer harbors high mortality despite chemoradiotherapy. Better patient selection for more personalized management may result in better treatment outcomes. We presume the ratio of maximum standardized uptake value (SUV) of metastatic lymph nodes to primary tumor (NTR) in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) may provide prognostic information and further stratification of these patients. METHODS: The patients with non-metastatic and unresectable esophageal squamous cell carcinoma (SCC) receiving FDG PET/CT staging and treated by chemoradiotherapy were retrospectively reviewed. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for NTR. Kaplan-Meier method and Cox regression model were used for survival analyses and multivariable analyses, respectively. RESULTS: From 2010 to 2016, 96 eligible patients were analyzed. The median follow-up time was 10.2 months (range 1.6 to 83.6 months). Using ROC analysis, the best NTR cut-off value was 0.46 for prediction of distant metastasis. The median distant metastasis-free survival (DMFS) was significantly lower in the high-NTR group (9.5 vs. 22.2 months, p = 0.002) and median overall survival (OS) (9.5 vs. 11.6 months, p = 0.013) was also significantly worse. Multivariable analysis revealed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR] 1.81, p = 0.023) and OS (HR 1.77, p = 0.014). CONCLUSIONS: High pretreatment NTR predicts worse treatment outcomes and could be an easy-to-use and helpful prognostic factor to provide more personalized treatment for patients with non-metastatic and unresectable esophageal SCC.

Can 18F-NaF PET/CT before Autologous Stem Cell Transplantation Predict Survival in Multiple Myeloma?

There is an unmet need for positron emission tomography (PET) radiotracers that can image bone disease in multiple myeloma (MM) in a more sensitive and specific way than the widely used 18F-fluorodeoxyglucose (18F-FDG). Sodium fluoride (18F-NaF) is a highly sensitive tracer of bone reconstruction, evolving as an important imaging agent for the assessment of malignant bone diseases. We attempted to investigate for the first time the prognostic significance of 18F-NaF PET/CT in newly diagnosed, symptomatic MM patients planned for autologous stem cell transplantation (ASCT). Forty-seven patients underwent dynamic and static PET/CT with 18F-NaF before treatment. After correlation with the respective findings on CT and 18F-FDG PET/CT that served as reference, the 18F-NaF PET findings were compared with established factors of high-risk disease, like cytogenetic abnormalities as well as bone marrow plasma cell infiltration rate. Furthermore, the impact of 18F-NaF PET/CT on progression-free survival (PFS) was analyzed. Correlation analysis revealed a moderate, significant correlation of the 18F-NaF parameters SUVaverage and K1 in reference tissue with bone marrow plasma cell infiltration rate. However, no significant correlation was observed regarding all other 18F-NaF PET parameters. Survival analysis revealed that patients with a pathologic 18F-NaF PET/CT have a shorter PFS (median = 36.2 months) than those with a physiologic scan (median = 55.6 months) (p = 0.02). Nevertheless, no quantitative 18F-NaF parameter could be shown to adversely affect PFS. In contrast, the respective analysis for quantitative dynamic 18F-FDG PET/CT revealed that the parameters SUVmax, fractional blood volume (VB), k3 and influx from reference tissue as well as SUVaverage from MM lesions had a significant negative impact on patient survival. The herein presented findings highlight the rather limited role of 18F-NaF PET/CT as a single PET approach in MM.