Average Standardized Uptake Value Research Articles

Abstract P043: Correlation Between Blood Pressure And Left Ventricular Metabolism In HIV Individuals With And Without Cocaine Use As Assessed By FDG-PET/CT

Objectives: Elevated blood pressure from cocaine can increase left ventricular (LV) metabolic activity, leading to structural changes such as hypertrophy. We aimed to assess the association between blood pressure and LV myocardial uptake of FDG, hypothesizing that HIV individuals with raised blood pressure will have higher FDG uptake. Methods: University of Pennsylvania enrolled patients with HIV on antiretroviral therapy with viral load <200 copy/ml. Cocaine usage in moderate to high amounts (cocaine disease score≥5) was subsequently documented. Full body PET scans were acquired 120 minutes post-injection of 18F-FDG(15 mCi) with low-dose CT scans for attenuation correction. Patients with imaging artifacts were excluded from the analysis. Regions of interest were drawn on axial slices using computer software (OsirixMD, v9.0.02) around LV myocardium. Average standard uptake value means (aSUVmean) were calculated for each patient. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained prior to imaging; mean arterial pressure (MAP) was subsequently calculated. Linear regressions and Mann-Whitney U tests were employed for statistical analysis. Results: aSUVmean was higher in HIV patients with cocaine use (U(Ncocaine = 11, Nno cocaine=11) = 93, p=0.0336). In patients with cocaine use, there was a positive correlation between blood pressure and aSUVmean (SBP: r=0.70, p=0.0164; DBP: r=0.69, p=0.0185; MAP: r=0.72, p=0.0120). No significant correlations were found in HIV patients without cocaine use (SBP: r=0.03, p=0.9239; DBP: r=-0.50, p=0.1153; MAP: r=-0.32, p=0.3345). Conclusions: LV myocardial metabolism was more strongly positively correlated with blood pressure in HIV patients using cocaine compared to HIV patients without cocaine. These data suggest FDG-PET/CT can be used to monitor LV metabolic activity and allow for timely assessment of structural changes caused by cocaine use and hypertension.

Simplified dual time point FDG-PET/computed tomography for determining dignity of pancreatic lesions.

Predicting the dignity of pancreatic lesions is still a diagnostic challenge. The differentiation between benign changes in chronic pancreatitis from pancreatic cancer remains difficult. Therefore, the aim of this study was to evaluate whether early dual time point kinetics of pancreatic lesions in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) may be helpful to differentiate pancreatic lesions. We prospectively analyzed 64 patients (pancreatic cancer n = 45 and chronic pancreatitis n = 19) scheduled for dual time point FDG-PET/computed tomography scan for pancreatic lesions from 2005 to 2014. Studies were performed 60 and 90 minutes after application of F-FDG. Histological samples were collected for all patients, either by resection or by biopsy. Semiquantitative analysis was performed using the minimum, the maximum, and the average standardized uptake value (SUV) from the two different sets of images. To increase sensitivity and specificity, a formula addressing the weighting of standardized uptake values was created. With a sensitivity of 82.6%, specificity of 77.8%, accuracy of 79.7%, positive predictive value of 90.5%, and negative predictive value of 63.6% SUVmax@time1 > 3.45 was the most reliable single quantitative parameter for malignancy of the pancreatic lesions. Weighting of standardized uptake values produced a formula that showed an even better profile. In patients with suspicious pancreatic lesions, the simplified dual time point FDG-PET/computed tomography may represent a valuable diagnostic tool in characterizing pancreatic lesions.

Spinal cord hypermetabolism extends to skeletal muscle in amyotrophic lateral sclerosis: a computational approach to [18F]-fluorodeoxyglucose PET/CT images

PurposeAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to neuromuscular palsy and death. We propose a computational approach to [18F]-fluorodeoxyglucose (FDG) PET/CT images to analyze the structure and metabolic pattern of skeletal muscle in ALS and its relationship with disease aggressiveness.Materials and methodsA computational 3D method was used to extract whole psoas muscle’s volumes and average attenuation coefficient (AAC) from CT images obtained by FDG PET/CT performed in 62 ALS patients and healthy controls. Psoas average standardized uptake value (normalized on the liver, N-SUV) and its distribution heterogeneity (defined as N-SUV variation coefficient, VC-SUV) were also extracted. Spinal cord and brain motor cortex FDG uptake were also estimated.ResultsAs previously described, FDG uptake was significantly higher in the spinal cord and lower in the brain motor cortex, in ALS compared to controls. While psoas AAC was similar in patients and controls, in ALS a significant reduction in psoas volume (3.6 ± 1.02 vs 4.12 ± 1.33 mL/kg; p < 0.01) and increase in psoas N-SUV (0.45 ± 0.19 vs 0.29 ± 0.09; p < 0.001) were observed. Higher heterogeneity of psoas FDG uptake was also documented in ALS (VC-SUV 8 ± 4%, vs 5 ± 2%, respectively, p < 0.001) and significantly predicted overall survival at Kaplan–Meier analysis. VC-SUV prognostic power was confirmed by univariate analysis, while the multivariate Cox regression model identified the spinal cord metabolic activation as the only independent prognostic biomarker.ConclusionThe present data suggest the existence of a common mechanism contributing to disease progression through the metabolic impairment of both second motor neuron and its effector.

Spinal tuberculosis: proposed spinal infection multidisciplinary management project (SIMP) flow chart revision.

We propose a revised flow chart of spinal infection multidisciplinary management project (SIMP) aimed to standardize the diagnostic process and management of spinal tuberculosis (TB). We reviewed data from all TB cases with osteoarticular involvement treated at a large tertiary teaching hospital in Bologna, Northern Italy, from January 2013 to December 2017. We cross-linked notified osteoarticular TB cases with SIMP database and we analysed clinical, diagnostic, and treatment data of all cases managed by SIMP. Osteoarticular TB accounted for the 7.8% (n=40) of all TB cases notified between 2013 and 2017 (N=513). Among the identified cases, 52% (n=21/40) had spine involvement: all were enrolled and evaluated by SIMP multidisciplinary group. Females accounted for 57% (12/21) of patients, the median age was 52 years (range 24-82). In the 67% (n=14/21) of cases, the major clinical symptom of spinal TB was back pain reported for a median of 4.5 months (range 1-12 months) before hospital admission. The interferon gamma release assay was positive in 75% (n=16/21) of patients. All patients performed MRI with gadolinium, which indicated spondylodiscitis in 90%. 18F-FDG-PET/CT revealed average maximum standardized uptake value (SUV max) of 12.54 (range 5.3-22) in 17/19 (89.5%). Bacteriological confirmation of TB was obtained in 86% of cases (n=18/21). One-third of patients (7/21) underwent surgery and 95% successfully completed the anti-TB treatment. Our data reveal that a multidisciplinary approach to spine tuberculosis facilitates early and accurate diagnosis and can improve medical and surgical management of this disease.

18F-FDG-PET/CT in measuring volume and global metabolic activity of thigh muscles: a novel CT-based tissue segmentation methodology.

We present a novel computed tomography-based tissue segmentation methodology for determining volume and global uptake of FDG of the thigh muscles and correlate these parameters with age. A total of 71 subjects from a prospective clinical trial (NCT01724749) were included. PET/CT scans were acquired 180 minutes after intravenous injection of FDG. A 3D growing region algorithm with neighborhood Hounsfield unit threshold between one and 150 was used to highlight the muscle. FDG uptake was expressed as the average mean standardized uptake value normalized for lean body mass (average SULmean). Femur volume was used to normalize thigh muscle volume to calculate normalized volume and correlate with age. We found a significant negative correlation between normalized volume and age (left side r = -0.262, P = 0.02; right side r = -0.286, P = 0.01). No statistically significant difference was found between SUL and age or between SUL and BMI. There was no statistically significant difference in muscle volume on the two sides. Statistically significant difference was noted in the global metabolic activity (SUL) between the two sides (left 0.39 ± 0.06, right 0.42 ± 0.08, P < 0.001), with 56/71 (78.8%) subjects having higher uptake on the right side. FDG-PET/CT using CT-based segmentation is a novel imaging modality assessing the volume and global metabolic activity of the thigh muscles. It could be possible to utilize this methodology for the research and understanding of lower limb muscle pathophysiology.

Immunization with the Gly1127-Cys1140 amino acid sequence of the LRP1 receptor reduces atherosclerosis in rabbits. Molecular, immunohistochemical and nuclear imaging studies.

Background: The LRP1 (CR9) domain and, in particular, the sequence Gly1127-Cys1140 (P3) plays a critical role in the binding and internalization of aggregated LDL (agLDL). We aimed to evaluate whether immunization with P3 reduces high-fat diet (HFD)-induced atherosclerosis.Methods: Female New Zealand White (NZW) rabbits were immunized with a primary injection and four reminder doses (R1-R4) of IrP (irrelevant peptide) or P3 conjugated to the carrier. IrP and P3-immunized rabbits were randomly divided into a normal diet group and a HFD-fed group. Anti-P3 antibody levels were determined by ELISA. Lipoprotein profile, circulating and tissue lipids, and vascular pro-inflammatory mediators were determined using standardized methods while atherosclerosis was determined by confocal microscopy studies and non-invasive imaging (PET/CT and Doppler ultrasonography). Studies treating human macrophages (hMΦ) and coronary vascular smooth muscle cells (hcVSMC) with rabbit serums were performed to ascertain the potential impact of anti-P3 Abs on the functionality of these crucial cells.Results: P3 immunization specifically induced the production of anti-P3 antibodies (Abs) and did not alter the lipoprotein profile. HFD strongly induced cholesteryl ester (CE) accumulation in the aorta of both the control and IrP groups, and their serum dose-dependently raised the intracellular CE of hMΦ and hcVSMC, promoting TNFR1 and phospho-NF-kB (p65) overexpression. These HFD pro-inflammatory effects were dramatically decreased in the aorta of P3-immunized rabbits and in hMΦ and hcVSMC exposed to the P3 rabbit serums. Microscopy studies revealed that P3 immunization reduced the percentage of lipids, macrophages, and SMCs in the arterial intima, as well as the atherosclerotic extent and lesion area in the aorta. PET/CT and Doppler ultrasonography studies showed that the average standardized uptake value (SUVmean) of the aorta and the arterial resistance index (ARI) of the carotids were more upregulated by HFD in the control and IrP groups than the P3 group.Conclusions: P3 immunization counteracts HFD-induced fatty streak formation in rabbits. The specific blockade of the LRP1 (CR9) domain with Anti-P3 Abs dramatically reduces HFD-induced intracellular CE loading and harmful coupling to pro-inflammatory signaling in the vasculature.

Risk factors of tumor relapse in patients with clinical stages 1–3 esophageal squamous cell carcinoma after curative surgery

Background: The aim of this study was to determine the risk factors for disease progression in patients with clinical stages 1–3 squamous cell carcinoma (SCC) of the esophagus after curative surgery. Methods: This is a retrospective study of postoperative risk factors for patients with SCC after esophagectomy. The factors related to disease progression, including stage, clinical tumor response, operation types, number of resected lymph node number, standard uptake value (SUV), tumor differentiation, lymphovascular space invasion, perineural invasion, extracapsular invasion, and tumor regression grade, were analyzed. Results: A total of 73 patients treated between 2011 and 2015 were included in the study. Twenty-six patients developed disease recurrence, including 10 locoregional and 16 distant metastases. Clinical tumor response, procedure types, tumor differentiation, extracapsular invasion, and average standard uptake value (SUVmax) were significantly associated with overall survival. On multivariate analysis, clinical tumor response (P = 0.044), minimally invasive esophagectomy (MIE) (P = 0.006), and tumor differentiation (P = 0.042) remained independent predictors for the disease progression. Conclusions: Clinical tumor response, MIE, tumor differentiation, extracapsular invasion, and average SUVmax of tumor (postconcurrent chemoradiotherapy) were independent predictors for the disease progression. Our findings put forward the postoperative predictors of disease progression in esophageal SCC to identify high-risk patients and deliver proper treatment.

Association of neuroinflammation with episodic memory: a [11C]PBR28 PET study in cognitively discordant twin pairs.

Alzheimer’s disease is associated with chronic response of innate immune system, referred as neuroinflammation. PET radioligands binding to the 18 kDa translocator protein are potential biomarkers of neuroinflammation. Translocator protein PET studies in mild cognitive impairment and Alzheimer’s disease have indicated controversial results, possibly reflecting interindividual variation and heterogeneity of study populations. We controlled for genetic and environmental effects by studying twin pairs discordant for episodic memory performance. Episodic memory impairment is a well-known cognitive hallmark of early Alzheimer’s disease process. Eleven same-sex twin pairs (four monozygotic pairs, six female pairs, age 72–77 years) underwent [11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28) PET imaging, structural magnetic resonance imaging and neuropsychological testing in 2014–17. Main PET outcome was the volume-weighted average standardized uptake value of cortical regions vulnerable to Alzheimer’s disease pathology. Ten pairs were discordant for episodic memory performance. In the eight pairs with identical translocator protein genotype, twins with poorer episodic memory had ∼20% higher cortical [11C]PBR28 binding compared with their better-performing co-twins (mean intra-pair difference 0.21 standardized uptake value, 95% confidence interval 0.05–0.37, P = 0.017). The result remained the same when including all discordant pairs and controlling for translocator protein genotype. Increased translocator protein PET signal suggests that increased microglial activation is associated with poorer episodic memory performance. Twins with worse episodic memory performance compared with their co-twins had on average 20% higher uptake of the neuroinflammatory marker translocator protein PET tracer 11[11C]PBR28. The findings support a negative association between neuroinflammation and episodic memory and the use of translocator protein positron emission tomography as a useful indicator of Alzheimer’s disease process.

18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification

To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention. This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m2): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUVmean; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUVmean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUVmax) did not differ between patients and controls. SUVmean correlated with age and BMI among females (age, partial R2 = 0.16, P = 0.001; BMI, partial R2 = 0.12, P = 0.004) and males (age, partial R2 = 0.28, P < 0.0001; BMI, partial R2 = 0.22, P < 0.0001). Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUVmean, but were not sensitive enough to predict patient status. SUVmean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries. ClinicalTrials.gov (NCT01724749).

Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis in Multiple Myeloma and Stratification of Revised International Staging System Stage II

Introduction: Multiple myeloma (MM) is a heterogeneous malignant plasma cell (PC) disorder and the survival ranges from several months to &gt; 10-years. Revised International Staging System (R-ISS) has been reported to define subgroups of patients with MM with different prognosis, however, most of the patients were classified as R-ISS stage II, thus, it includes a heterogenous population with various risk factors. 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) allows the direct assessment of metabolic tumor burden in various malignancies. Therefore, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volumetric parameters applicable to 18F-FDG PET/CT, are emerging tools for MM prognostication. This study aimed to determine the value of MTV and TLG using 18F-FDG PET/CT in the prognostication and to determine the high-risk patients in R-ISS stage II in combination with R-ISS and MTV and TLG. Methods: A total of 191 consecutive patients with newly diagnosed MM (NDMM) who underwent baseline whole-body 18F-FDG PET/CT and R-ISS between January 2009 and June 2019 at Kameda Medical Center, Kamogawa-shi, Japan, were retrospectively analyzed. Del(17p), translocation t(4; 14), and t(14;16) detected by interphase fluorescent in situ hybridization were considered high-risk chromosomal abnormalities. All patients underwent combination chemotherapy using novel agents. 18F-FDG PET/CT was performed using dedicated PET/CT scanners (Discovery ST Elite Performance; GE Healthcare, Milwaukee, USA). The standard uptake value (SUV) was normalized according to the injected dose and lean body mass. The baseline SUVmax of all lesions was recorded, and the highest value was considered as the SUVmax of the patient. MTV was defined as the myeloma lesions volume visualized on PET/CT scans with SUV greater than or equal to the fixed absolute threshold of SUV = 2.5. TLG was calculated as the sum of the product of average SUV (SUVmean) and MTV of all lesions. Computer‐aided analysis of PET/CT images for MTV and TLG calculations was performed using an open-source software application of Metavol (Hokkaido University, Sapporo, Japan). Nine patients were excluded because MTV data could not be retrieved. Ultimately, 182 patients were included in our analysis. Written informed consent was obtained from all patients. Results: Whole-body MTV and TLG ranged from 0 to 2440.7 mL (median; 34.2 mL) and from 0 to 12582.4 g (median; 97.0 g). The best cut-off values of MTV and TLG that discriminate the survival using a receiver-operating-characteristic curve analysis were 56.4 mL and 166.4 g, respectively. Both MTV and TLG can be used to stratify patients according to cut-off values using Kaplan-Meier survival curves and log-rank test. At a median follow-up of 32 months, the overall survival (OS) and progression-free survival (PFS) of patients with a lower cut-off value of MTV (≤56.4 mL) had better survival compared to those with a higher cut-off value (&gt;56.4 mL) [not reached (NR) vs 52.9 months for OS, p=0.003, and 37.3 vs 23.8 months for PFS, p=0.019, respectively]. Similarly, the OS and PFS of patients with a baseline lower cut-off value of TLG (≤166.4 g) showed better survivals compared to those with a higher cut-off value (&gt;166.4 g) (NR vs 54.3 months for OS, p=0.0047, and 37.3 vs 28.8 months for PFS, p=0.012, respectively). Although R-ISS can stratify the OS of patients into 3 groups (Figure 1A), we explored the clinical variables and MTV and TLG to further identify the high-risk patients among the R-ISS stage II. We divided the following 4 groups: R-ISS stage I; R-ISS stage II with a lower cut-off value of MTV or TLG; R-ISS stage II with a higher cut-off value of MTV or TLG; and R-ISS stage III. The median OS was NR in R-ISS stage I, 94.9 months in R-ISS stage II with a lower cut-off value of MTV, 54.3 in R-ISS stage II with a higher cut-off value of MTV, and 50.4 in R-ISS stage III (Figure 1B); the median PFS were NR, 32.0, 30.2, and 29.3 months, respectively. Other clinical factors including age, hemoglobin, creatinine, and stem cell transplantation were not associated with the prognosis of these patients. Conclusion: Our findings demonstrated that MTV and TLG calculated from pretreatment PET/CT were useful for risk stratification in patients with NDMM. By identifying patients with stage II and a poor prognosis, it may be possible to select patients who are candidates for aggressive treatment. Disclosures Matsue: Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K: Honoraria; Ono Pharmaceutical: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Celgene: Honoraria.

Prognostic Implications of Metabolic Total Volume and Total Lesion Glycolysis Assessed By PET/CT Combined with High Levels of Bone Marrow Plasma Cells Percentages As a Potential Risk Model in Patients with Newly Diagnosed Multiple Myeloma

Introduction: Multiple myeloma (MM) is a heterogeneous malignant plasma cell (PC) disorder and the survival ranges from several months to &gt; 10-years. Several risk stratification systems such as the Revised International Staging System (R-ISS) have been developed. PET/CT allows the direct assessment of metabolic tumor burden in various malignancies. Therefore, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volumetric parameters applicable to PET/CT, are emerging tools for MM prognostication. This study was aimed to determine the value of MTV and TLG using PET/CT in the prognostication and in combination with various hematologic parameters such as bone marrow PC (BMPC) percentages and circulating tumorous PCs (CPCs) to identify the patients with high-risk features. Methods: A total of 196 consecutive patients with newly diagnosed MM (NDMM) who underwent baseline whole-body PET/CT between January 2009 and June 2019 at Kameda Medical Center, Kamogawa-shi, Japan, were retrospectively analyzed. PET/CT was performed using dedicated PET/CT scanners (Discovery ST Elite Performance; GE Healthcare, Milwaukee, USA). The standard uptake value (SUV) was normalized according to the injected dose and lean body mass. The baseline SUVmax of all lesions was recorded, and the highest value was considered as the SUVmax of the patient. MTV was defined as the myeloma lesions volume visualized on PET/CT scans with SUV greater than or equal to the fixed absolute threshold of SUV = 2.5. TLG was calculated as the sum of the product of average SUV (SUVmean) and MTV of all lesions. Computer‐aided analysis of PET-CT images for MTV and TLG calculations was performed using an open-source software application of Metavol (Hokkaido University, Sapporo, Japan). The CPCs were measured using an 8-color flowcytometry and reported as the percentage per total mononuclear cells using the monoclonal antibodies of CD19, 38, 45, 56, 117, 200, κ, λ, and CD138. The BMPC was calculated by counting the percentages of CD138-stained PCs among the all nucleated cells on bone marrow biopsy samples. Eleven patients (13.8%) were excluded because the MTV data could not be retrieved. Ultimately, 185 patients were included in our analysis. Written informed consent was obtained from all patients. Results: Among the 185 patients, 28 patients (15.1%) were negative for avid lesion on PET/CT. Whole-body MTV and TLG ranged from 0 to 2440.7 mL, with a median of 34.2 mL and from 0 to 12582.4 g, with a median of 97.0 g, respectively. The best cut-off values of MTV and TLG that discriminate the survival using a receiver-operating-characteristic curve analysis were 56.4 mL and 166.4 g, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with a lower cut-off value of MTV (≤56.4 mL) had better survival with not reached (NR) and 37.3 months as compared to those with a higher cut-off value (&gt;56.4 mL) that reached 52.9 and 23.8 months, respectively (p=0.003 and 0.019). Similarly, the OS and PFS of patients with a lower cut-off value of TLG (≤166.4 g) showed better survivals with NR and 37.3 months as compared to those with a higher cut-off value (&gt;166.4 g) that reached 54.3 and 28.8 months, respectively (p=0.0047 and 0.012). Next, we explored the prognostic impact of the clinical variables including MTV or TLG, CPCs, and BMPC. High levels of CPCs and BMPCs levels were defined as ≥0.018% of the total mononuclear cells and BMPCs of ≥57%, respectively. Univariate analysis showed that age≥70, serum creatinine≥2.0 mg/dL, R-ISS stage 3, higher cut-off value of MTV, and higher cut-off value of TLG were the associated with shorter OS. To measure the tumor volume with accuracy, we combined BMPC or CPCs and MTV or TLG. On multivariate analysis, age≥70 and the combination of higher cut-off value of MTV or TLG and high level of BMPC percentage were significantly associated with shorter OS [Hazard Ratio (HR) 2.12, p=0.038, HR 2.66, p=0.027 and HR 2.57, p=0.029, respectively] and PFS (Not assessed, HR 2.52, p=0.018 and HR 2.7, p= 0.011, respectively) (Figure 1). Conclusion: Our findings demonstrated that MTV and TLG calculated from pretreatment PET/CT were useful for risk stratification in patients with NDMM when combined with BMPC. The prognostic performance of the combined high-burden of TLG or MTV and high levels of BMPC were independent of the established risk factors. Disclosures Matsue: Novartis Pharma K.K: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Ono Pharmaceutical: Honoraria.

Baseline Total Lesion Glycolysis Combined with Interim PET/CT Is a Robust Predictor of Outcome in Patients with Peripheral T-Cell Lymphoma

Background: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been widely used for the initial staging and monitoring of the response in patients with malignant lymphomas, including peripheral T-cell lymphoma (PTCL). FDG PET/CT performed during a course of chemotherapy (interim PET, iPET) indicates early response and has been found to have prognostic value in various lymphoma subtypes. In addition to early treatment response, baseline characteristics including tumor burden and metabolic activity also significantly impact outcomes. Recently, volume-based metabolic assessments using PET/CT, including the total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), have emerged as new assessment tools. In this study, we investigated the predictive value of baseline TMTV and TLG in PTCL, and ascertained whether iPET response can be combined with these parameters to improve risk stratification. Methods: Patients with confirmed PTCL treated at Kameda Medical Center were retrospectively analyzed. The inclusion criteria included: a confirmed histological diagnosis of PTCL; pretreatment PET/CT and iPET evaluation; and anthracycline-based chemotherapy as first-line treatment. TMTV was defined as the volume of lymphoma visualized on PET/CT with a standardized uptake value (SUV) greater than or equal to the fixed absolute threshold of 2.5. TLG was calculated as the sum of the product of the average SUV (SUVmean) and MTV of all lesions. The computer-aided analyses of the PET/CT images for TMTV and TLG calculations were performed using an open-source software application Metavol (Hokkaido University, Sapporo, Japan). All iPET scans were defined as PET/CT scans performed after 2-4 cycles of chemotherapy. Response on iPET was assessed using the Deauville 5-point scale, with a score of 4-5 reflecting positivity. Results: Of the 107 patients with PTCL in our lymphoma cohort, we excluded adult T-cell leukemia/lymphoma, extranodal NK/T cell lymphoma, and cutaneous T-cell lymphoma, due to the different treatment strategies. Finally, 63 patients were enrolled in this study, including 30 with PTCL not otherwise specified (PTCL-NOS), 28 with angioimmunoblastic T-cell lymphoma (AITL), 4 with ALK-negative anaplastic large cell lymphoma (ALCL), and one with ALK-positive ALCL. The median age was 73 (range: 46-88) years. The majority of patients were treated with CHOP or CHOP-like chemotherapy. Consolidation therapy with stem cell transplantation was performed only in seven patients (11%) as our patients had a relatively higher age. After a median follow-up period of 35 months, the 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 30% and 51%, respectively. First, we assessed the prognostic value of the TMTV and TLG. The median baseline TMTV and TLG values were 423 cm3 (range, 21-3012 cm3) and 1980 (range, 56-21400), respectively. The optimal cutoff values determined using ROC curve analysis were 389 cm3 for TMTV and 875 for TLG. A high baseline TMTV was associated with worse PFS (hazard ration [HR], 2.244; 95% confidence interval [CI], 1.195-4.212; P = .01) and OS (HR, 3.358; 95% CI, 1.502-7.503; P = .002). Moreover, high baseline TLG were highly predictive of worse PFS (HR, 3.767; 95% CI, 1.666-8.517; P = .0005) and OS (HR, 4.722; 95% CI, 2.032-10.97; P &lt;.0001) (Figure 1). Next, we confirmed the prognostic value of the iPET findings. The iPET results were negative in 38 of 63 (60%) cases. In the univariate analysis, iPET positivity was predictive of worse PFS (HR, 2.177; 95% CI, 1.203-3.940; P = .009) and OS (HR, 4.931; 95% CI, 2.395-10.15; P &lt;.0001) (Figure 2). In the multivariate analysis testing TLG or TMTV with iPET results and PIT scores, only high TLG and positive iPET independently predicted both worse OS and PFS. Thus, we constructed a prognostic model combining the baseline TLG and iPET results. This model showed that patients with low baseline TLG values and negative iPET results had superior outcomes, with 5-year PFS of 72% and 5-year OS of 90% (Figure 3). While 5-year PFS and OS for those with high TLG and positive iPET were both 0%. Conclusion: Baseline TLG and iPET results are both independent prognostic factors in PTCL. Furthermore, TLG combined with iPET more accurately predicted survival in PTCL. This information may help the development of a risk-adapted treatment strategy for patients with PTCL. Disclosures Takahashi: Novartis Pharmaceuticals: Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; Chug Pharmaceuticals: Research Funding; Otsuka Pharmaceutical: Research Funding, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding, Speakers Bureau; Eisai Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Speakers Bureau; Asahi Kasei Pharma: Research Funding; Ono Pharmaceutical: Research Funding. Matsue:Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K: Honoraria; Ono Pharmaceutical: Honoraria.

68Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer-a modified protocol compared with the common protocol.

68Ga-PSMA-11 PET/CT is commonly performed at 1 h post injection (p.i.). However, various publications have demonstrated that most prostate cancer (PC) lesions exhibit higher contrast at later imaging. The aim of this study was to compare the "common" protocol of 68Ga-PSMA-11 PET/CT with a modified protocol. In 2017, we used the following scanning protocol for 68Ga-PSMA-11 PET/CT in patients with recurrent PC: acquisition at 1 h p.i. without further preparations. From 2018, all scans were conducted at 1.5 h p.i. In addition, patients were orally hydrated with 1 L of water 0.5 h p.i. and were injected with 20 mg of furosemide 1 h p.i. Both protocols including 112 patients (2017) and 156 (modified protocol in 2018) were retrospectively compared. Rates of pathologic scans, maximum standardized uptake values (SUVmax), and tumor contrast (ratio lesion-SUVmax/background-SUVmean) as well as average standardized uptake values (SUVmean) of urinary bladder were analyzed. Both tumor contrast and tracer uptake were significantly (p < 0.001) higher in the novel protocol. Although statistically not significant, the rates of pathologic scans were also higher in the modified protocol: 76.3% vs. 68.8% for all PSA values including 38.9% vs. 25.0% for PSA < 0.5 ng/ml and 60.0% vs. 56.7% for PSA > 0.5-≤ 2.0 ng/ml. Average SUVmean of the urinary bladder was significantly (p < 0.001) lower with the modified protocol. The modified protocol, which includes a combination of delayed image acquisition at 1.5 h p.i., hydration, and furosemide resulted in higher tumor contrast and seems to have the potential to increase the rates of pathological scans, especially at low PSA levels.

The value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in evaluating the stability of atherosclerotic plaques

Objective: Positron emission tomography-computed tomography (PET-CT) has been used to quantify inflammatory response in the body. The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques. Methods: Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group, with 10 rabbits in each group. Rabbits in both groups were fed with a high fat diet for 20 weeks, and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week. Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day. At the 8th week, thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits. Blood was drawn at the 3rd and the 20th week, respectively, to measure blood lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). At the end of experiment, survival animals were scanned by (18)F-FDG PET-CT, and the average and maximum standard uptake values (SUVmean, SUVmax) of aortic segments were measured. Thereafter, the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry. The pathological indexes were measured and compared. Results: At the end of experiment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hs-CRP [ (4.58±0.51) ng/ml vs.(5.87±0.66) ng/ml, P<0.01], MMP-9[ (43.93±2.16) ng/ml vs. (50.77±2.32) ng/ml, P<0.01], SUVmean (0.59±0.15 vs. 0.68±0.20, P<0.05) , SUVmax (0.68±0.20 vs. 0.81±0.27, P<0.05) , plaque area [ (0.36±0.24) mm(2) vs. (0.50±0.34) mm(2), P<0.05) ] and density of macrophage[ (4.34±1.54) % vs. (5.65±1.89) %, P<0.01] in the atorvastatin intervention group were significantly lower than those in the control group. In contrast, fiber cap thickness of the plaque[ (4.12±0.66) μm vs. (2.96±0.37) μm, P<0.01] in the atorvastatin intervention group was higher than that of the control group, and the difference was statistically significant. The arterial plaque areas were positively correlated with SUVmean (r=0.27, P<0.05) and SUVmax (r=0.43, P<0.01) . Fiber cap thickness was negatively correlated with SUVmean (r=-0.38, P<0.05) and SUVmax (r=-0.47, P<0.01) . The density of macrophage were positively correlated with SUVmean (r=0.52, P<0.01) and SUVmax (r=0.51, P<0.01) . Conclusion: (18)F-FDG PET/CT can be used to evaluate the efficacy of atorvastatin by the stability of atherosclerotic plaques.

1374. Diagnostic Utility of Whole Body Positron Emission Tomography-Computerized Tomography (PET-CT) in Patients with Suspected Central Nervous System Tuberculosis: A Retrospective, Descriptive Study

BackgroundThere is difficulty in diagnosing central nervous system (CNS) tuberculosis (TB) in the early stages because features mimic viral and pyogenic meningitis. There is a need to determine alternate methods to diagnose CNS TB. Whole-body PET-CT, used mainly in oncology, has shown promise in the detection of tuberculosis and monitoring response to anti-tuberculous therapy. Utility in CNS TB is unexplored.MethodsRetrospective, cohort, single-center study. Patients were included if they fulfilled the following criteria: (1) Probable/possible tuberculous meningitis as per the Lancet Consensus Score; (2) undergone whole-body PET-CT with 18-fluorodeoxyglucose and intravenous contrast; (3) less than one week of anti-tuberculous therapy at the time of PET-CT; (4) clinical response to antituberculous treatment and steroids; (5) no other etiological agent identified.ResultsWe identified 9 patients that fulfilled the above criteria. 5 of these patients were immunosuppressed (4 had advanced AIDS, one patient was on immunosuppressive therapy). We found that 86.4% of patients (7 out of 9) had radiological features suggestive of probable active TB outside the CNS (Figure 1). Of these 7 patients, 5 patients had definite TB (defined as positive Ziehl–Neelsen stain or Gene Xpert MTB/RIF assay or culture for tubercle bacilli) outside the CNS while 2 had histopathological evidence of TB (granulomatous inflammation) (Figure 2). All strains of TB were rifampin sensitive. The sites of isolation of tuberculosis were (Figure 3). (a) Abdominal lymph node in 2 patients (40%); (b) cervical lymph node in 2 patients (40%); (c) sputum in 1 patient (20%). In patients with evidence of disease outside the CNS, the average maximum standardized uptake value (SUV Max) in diverse anatomical locations was 5.75 (range 1.9–11.2). The most frequent manifestation PET-CT manifestation suggestive of TB outside the CNS in decreasing order of frequency was cervical lymphadenopathy (in 55.5% of patients), pleural and pulmonary parenchymal involvement (44.4% in each), followed by mediastinal nodes and abdominal lymph nodes in 33.3% (Figure 4).ConclusionPET-CT is a valuable tool in treatment-naive (less than 1 week of anti-tuberculous therapy) patients with suspected CNS tuberculosis. A large proportion of patients have evidence of TB outside the CNS. Disclosures All authors: No reported disclosures.

Quantification of β cell mass using18F-FP-(+ )-DTBZ, a vesicular monoamine transporter type 2 radiotracer: A longitudinal study in type 1 diabetic rats

Objective The aim of this study was to investigate the possibility of type 2 vesicular monoamine transporter molecular probe, 18F-FP-(+ )-DTBZ, in the monitoring of total islet β cell mass in animal models. Methods Two groups of Wistar rats were included in this study. In the type 1 diabetes group (n=6), the streptozotocin (STZ) was intraperitoneally injected at a dose of 65 mg/kg, and the control group (n=6) was likewisely injected with an equal volume of saline, Micro- positron emission tomography (PET)/ computed tomography (CT) imaging was performed at these rats post injection of18F-FP-(+ )-DTBZ at 0.5, 1, 4, 6, and 12 months after STZ or saline injection, bodyweight and glucose level were also measured. Results The average standardized uptake values (SUV) in the pancreas in the type 1 diabetes rats were decreased significantly than that of the control group at 0.5, 1, and, 4 months (P 0.05) post injection of STZ and saline. Fasting blood glucose positively correlated with pancreatic SUV in the two groups at 0.5, 1, and 4 months (P<0.05) post injection of STZ and saline. Conclusion 18F-FP-(+ )-DTBZ PET imaging is a promising method for dynamic monitoring β cell mass in type 1 diabetic rats. Key words: Diabetes mellitus; Positron emission tomography; βcell mass; Type 2 vesicular monoamine transporter

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.

Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [18F]NaF PET/CT study.

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [18F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [18F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [18F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUVpeak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [18F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm3), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [18F]NaF uptake, with SUVpeak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [18F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.

Association between age, uptake of 18F-fluorodeoxyglucose and of 18F-sodium fluoride, as cardiovascular risk factors in the abdominal aorta.

We aimed to assess the feasibility of quantifying fluorine-18-fluorodexoglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) uptake in abdominal aorta and examine their association with age and cardiovascular risk factors. Our study comprised 123 subjects (48±14 years of age, 62 men) including 78 healthy volunteers and 45 patients with chest pain syndrome, who originally enrolled in the CAMONA study in Odense, Denmark (NCT01724749). All subjects underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and 18F-NaF PET/CT on separate days, 180min and 90min after administration of tracers, respectively. The global tracer uptake value (GTUV) in the abdominal aorta was determined as sum of the product of each slice area and its corresponding average standardized uptake value (SUV mean), divided by the sum of those slice areas. In addition, for each subject, the 10 years Framingham risk score (FRS) was calculated. The correlations between 18F-NaF and 18F-FDG GTUV with age and 10 years FRS were assessed in all, healthy and patient subjects. There was a significant, positive correlation between subjects' age and 18F-NaF GTUV (r=0.35, P<0.001), but not 18F-FDG GTUV (r=0.06, P=0.53). Also, there was a significant, positive correlation between 10 years FRS and 18F-NaF GTUV (r=0.30, P<0.001), but not 18F-FDG GTUV (r=0.01, P=0.95). Individual differences in 18F-FDG and 118F-NaF uptake were large in both healthy subjects and patients. In this study, the global uptake of 18F-NaF in abdominal aorta was positively associated with age and 10 years FRS in all subjects, healthy and patient groups, whereas the global uptake of 18F-FDG was not.

18F-Fluoride Positron Emission Tomographic Imaging of Penile Arteries and Erectile Dysfunction

BackgroundFluorine-18 sodium fluoride (NaF), a bone-seeking radiopharmaceutical used to detect osseous metastases, localizes in regions of microcalcification in atherosclerosis. ObjectivesTo determine if atherosclerosis of penile arteries plays a role in erectile dysfunction (ED), this study analyzed NaF images in prostate cancer patients. MethodsNaF positron emission tomography–computed tomography bone scans were evaluated in 437 prostate cancer patients (age 66.6 ± 8.7 years). Their urologic histories were reviewed for prevalent ED (diagnosed before the scan date) or incident ED (no ED at first scan, but developed during 1-year follow-up); patients with no ED (neither before the scan nor during follow-up) were included as a control group. A semicircular region of interest was set on the dorsal one-half of the penis (to avoid residual excreted activity in the urethra) on 5 contiguous slices at the base of the penis on positron emission tomography–computed tomography coronal reconstructions, and the average standardized uptake value (SUVmax) was described as NaF uptake. ResultsOf 437 patients, 336 (76.9%) had prevalent ED, 60 incident ED (13.7%), and 41 had no ED (9.4%). SUVmax in patients with prevalent (median 1.88; interquartile range [IQR]: 1.67 to 2.16) or incident (median 1.86; IQR: 1.72 to 2.08) ED was significantly higher than no ED (median 1.42; IQR: 1.25 to 1.54) patients (p < 0.001). After adjustment for other risk factors, the odds ratio of prevalent or incident ED was 25.2 (95% confidence interval: 9.5 to 67.0) for every 0.5-U increment in SUVmax with receptor operating characteristic area of 0.91 (95% confidence interval: 0.88 to 0.94). ConclusionsNaF uptake in penile vessels suggests that atherosclerosis is associated with ED in prostate cancer patients. The importance of NaF uptake needs to be tested in noncancer subjects and cause-effect relationship needs to be established.