SUV Peak Research Articles

Single-center analysis of cardiac amyloidosis using 99mTc-HMDP imaging for diagnosis and evaluation after tafamidis treatment.

This study aimed to evaluate the diagnostic performance of 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) imaging for cardiac amyloidosis and to demonstrate changes in cardiac uptake of 99mTc-HMDP after tafamidis treatment. Seventy-five patients with suspected cardiac amyloidosis who underwent 99mTc-HMDP imaging were included. We compared visual Perugini grades and semiquantitative heart-to-contralateral (H/CL) area ratios, myocardial maximum standardized uptake value (SUVmax), and peak of SUV (SUVpeak) between cardiac transthyretin amyloidosis (ATTR) and amyloid light-chain amyloidosis (AL). Comparison of interobserver reproducibility between H/CL ratios and myocardial SUVmax/SUVpeak was performed. H/CL ratio of 99mTc-HMDP and myocardial SUVmax/SUVpeak were compared before and after tafamidis administration for cardiac wild-type ATTR. Among 75 patients, 20 patients (26.7%) were visually positive based on Perugini grade. Fifteen and three patients were pathologically identified as cardiac ATTR and AL, respectively. ATTR group (n = 15) had significantly higher H/CL ratios of 99mTc-HMDP than AL group (n = 3) (P = 0.003). ATTR group (n = 15) had significantly higher myocardial SUVmax/SUVpeak of 99mTc-HMDP than AL group (n = 2) (P = 0.015). Myocardial SUVmax/SUVpeak had better interobserver reproducibility than H/CL ratios. After tafamidis treatment for cardiac wild-type ATTR, the decrease in myocardial SUVpeak was significant but not in H/CL ratios and myocardial SUVmax. H/CL ratio and SUVmax/SUVpeak in 99mTc-HMDP imaging were useful for diagnosing cardiac ATTR. Myocardial SUVpeak may be useful for monitoring changes in cardiac uptake after tafamidis treatment for cardiac ATTR.

18F]FDG and [68Ga]Ga-FAPI-04-Directed Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUVmean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007-1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

Correlation between 18 F-FDG PET/CT metabolic parameters and microvascular invasion before liver transplantation in patients with hepatocellular carcinoma.

Microvascular infiltration (MVI) before liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is associated with postoperative tumor recurrence and survival. MVI is mainly assessed by pathological analysis of tissue samples, which is invasive and heterogeneous. PET/computed tomography (PET/CT) with 18 F-labeled fluorodeoxyglucose ( 18 F-FDG) as a tracer has been widely used in the examination of malignant tumors. This study investigated the association between 18 F-FDG PET/CT metabolic parameters and MVI before LT in HCC patients. About 124 HCC patients who had 18 F-FDG PET/CT examination before LT were included. The patients' clinicopathological features and 18 F-FDG PET/CT metabolic parameters were recorded. Correlations between clinicopathological features, 18 F-FDG PET/CT metabolic parameters, and MVI were analyzed. ROC curve was used to determine the optimal diagnostic cutoff value, area under the curve (AUC), sensitivity, and specificity for predictors of MVI. In total 72 (58.06%) patients were detected with MVI among the 124 HCC patients. Univariate analysis showed that tumor size ( P = 0.001), T stage ( P < 0.001), maximum standardized uptake value (SUV max ) ( P < 0.001), minimum standardized uptake value (SUV min ) ( P = 0.031), mean standardized uptake value (SUV mean ) ( P = 0.001), peak standardized uptake value (SUV peak ) ( P = 0.001), tumor-to-liver ratio (SUV ratio ) ( P = 0.010), total lesion glycolysis (TLG) ( P = 0.006), metabolic tumor volume (MTV) ( P = 0.011) and MVI were significantly different. Multivariate logistic regression showed that tumor size ( P = 0.018), T stage ( P = 0.017), TLG ( P = 0.023), and MTV ( P = 0.015) were independent predictors of MVI. In the receiver operating characteristic curve, TLG predicted MVI with an AUC value of 0.645. MTV predicted MVI with an AUC value of 0.635. Patients with tumor size ≥5 cm, T3-4, TLG > 400.67, and MTV > 80.58 had a higher incidence of MVI. 18 F-FDG PET/CT metabolic parameters correlate with MVI and may be used as a noninvasive technique to predict MVI before LT in HCC patients.

Integrated 68 Ga-FAPI-04 PET/MR in Pancreatic Cancer : Prediction of Tumor Response and Tumor Resectability After Neoadjuvant Therapy.

This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P < 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.

68 Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results.

The aim of this study was to evaluate the diagnostic potential of 68 Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT). Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68 Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors' density. The group II was the postsurgical (n = 10) group in which the scanning was done before and after R-CT and used for treatment response evaluation. The quantitative analysis of 68 Ga-pentixafor PET/CT evaluated the mean SUV max , SUV mean , SUV peak , and T/B values. MR spectroscopy data evaluated the ratios of tumor metabolites (choline, NAA, creatine). 68 Ga-Pentixafor uptake was noted in all (n = 19) the patients. In the group I, the mean SUV max , SUV mean , SUV peak , and T/B values were found to be 4.5 ± 1.6, 0.60 ± 0.26, 1.95 ± 0.8, and 6.9 ± 4.6, respectively. A significant correlation ( P < 0.005) was found between SUV mean and choline/NAA ratio. Immunohistochemistry performed in 7/9 showed CXCR4 receptors' positivity (intensity 3 + ; stained cells >50.0%). In the group II, the mean SUV max at baseline was 4.6 ± 2.1 and did not differ (4.4 ± 1.6) significantly from the value noted at post-R-CT follow-up PET/CT imaging. At 6 months' clinical follow-up, 4 patients showed stable disease. SUV max and T/B ratios at follow-up imaging were lower (3.70 ± 0.90, 2.64 ± 1.35) than the corresponding values (4.40 ± 2.8; 2.91 ± 0.93) noted at baseline. Six (6/10) patients showed disease progression, and the mean SUV max , and T/B ratio in these patients were significantly ( P < 0.05) higher than the corresponding values at baseline and also higher than that noted in the stable patients. 68 Ga-Pentixafor PET/CT can be used for in vivo mapping of CXCR4 receptors in GBM. The technique after validation in a large cohort of patients may have added diagnostic value for the early detection of GBM recurrence and for treatment response evaluation.

PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease

AbstractBackgroundRho‐associated protein kinase 2 (ROCK2) activity is implicated in Alzheimer’s disease (AD) and other central nervous system (CNS) disorders 1. In this study, we investigated the relative expression levels of ROCK2 in APP/PS1 transgenic AD mice and age‐matched wild‐type (WT) C57BL/6J mice using the ROCK2‐specific PET radioligand, [11C]ROCK201.MethodsThe ROCK2 tracer [11C]ROCK201 was synthesized according to the previously published procedure 2. PET scans were performed in a Focus‐220 scanner on 12‐month‐old APP/PS1 transgenic mice (n = 8) and WT controls (n = 5). Self‐blocking scans were performed 10 min post injection (p.i.) of the unlabeled ROCK201 (i.v., 3.3 mg/kg). Regions of interest (ROIs) were extracted from the Ma‐Benveniste‐Mirrione mouse brain atlas and regional time‐activity curves (TACs) were obtained by applying template ROIs to the averaged PET images (0 to 60 min p.i.). Distribution volume ratio (DVR) values were generated using the simplified reference tissue model 2 (SRTM2) on the 60‐min dynamic PET imaging data, with cerebellum (CB) as the reference region. ROCK2 protein expression levels were assessed immunohistochemically in brain tissues of 12‐month‐old APP/PS1 (N = 3) and WT (N = 3) mice.ResultsUptake of [11C]ROCK201 was observed throughout the mouse brain, with peak SUV of 2.6. TACs were consistently higher in the hippocampus of APP/PS1 mice than controls, within 20 min p.i. (Fig. 1a). Reduced uptake was observed in self‐blocking studies, indicating specific binding of [11C]ROCK201 in the rodent brain (Fig. 1a). TACs were well fitted with SRTM2. Compared with age‐matched WT controls, the DVR(CB) in the hippocampus of APP/PS1 mice was 9.3% higher than that of WT mice (p = 0.03) (Fig. 1b). Consistent with PET imaging results, ROCK2 protein expression is elevated by 49±2% in the CA1 of APP/PS1 mice compared to that of WT mice (Fig. 1c).ConclusionsWe demonstrated the uptake and detection sensitivity of the radioligand [11C]ROCK201 in the mouse brain, with higher tracer uptake in the hippocampi of APP/PS1 mice as compared to WT mice, supporting the use of [11C]ROCK201 in preclinical AD drug discovery and development.

PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease

AbstractBackgroundRho‐associated protein kinase 2 (ROCK2) activity is implicated in Alzheimer’s disease (AD) and other central nervous system (CNS) disorders 1. In this study, we investigated the relative expression levels of ROCK2 in APP/PS1 transgenic AD mice and age‐matched wild‐type (WT) C57BL/6J mice using the ROCK2‐specific PET radioligand, [11C]ROCK201.MethodThe ROCK2 tracer [11C]ROCK201 was synthesized according to the previously published procedure 2. PET scans were performed in a Focus‐220 scanner on 12‐month‐old APP/PS1 transgenic mice (n = 8) and WT controls (n = 5). Self‐blocking scans were performed 10 min post injection (p.i.) of the unlabeled ROCK201 (i.v., 3.3 mg/kg). Regions of interest (ROIs) were extracted from the Ma‐Benveniste‐Mirrione mouse brain atlas and regional time‐activity curves (TACs) were obtained by applying template ROIs to the averaged PET images (0 to 60 min p.i.). Distribution volume ratio (DVR) values were generated using the simplified reference tissue model 2 (SRTM2) on the 60‐min dynamic PET imaging data, with cerebellum (CB) as the reference region. ROCK2 protein expression levels were assessed immunohistochemically in brain tissues of 12‐month‐old APP/PS1 (N = 3) and WT (N = 3) mice.ResultUptake of [11C]ROCK201 was observed throughout the mouse brain, with peak SUV of 2.6. TACs were consistently higher in the hippocampus of APP/PS1 mice than controls, within 20 min p.i. (Fig. 1a). Reduced uptake was observed in self‐blocking studies, indicating specific binding of [11C]ROCK201 in the rodent brain (Fig. 1a). TACs were well fitted with SRTM2. Compared with age‐matched WT controls, the DVR(CB) in the hippocampus of APP/PS1 mice was 9.3% higher than that of WT mice (p = 0.03) (Fig. 1b). Consistent with PET imaging results, ROCK2 protein expression is elevated by 49±2% in the CA1 of APP/PS1 mice compared to that of WT mice (Fig. 1c).ConclusionWe demonstrated the uptake and detection sensitivity of the radioligand [11C]ROCK201 in the mouse brain, with higher tracer uptake in the hippocampi of APP/PS1 mice as compared to WT mice, supporting the use of [11C]ROCK201 in preclinical AD drug discovery and development.

Improved Risk Prediction in DLBCL By Combining Clinical and PET Features with Interim PET Assessment

Background: Accurate detection of patients at high risk of treatment failure following frontline immunochemotherapy in diffuse large B-cell lymphoma (DLBCL) is of paramount importance as these patients might benefit from early treatment escalation. Recently, we introduced the IMPI prognostic model based on metabolic tumor volume (MTV), age and stage that outperformed the international prognostic index (IPI). However, radiomic features such as Dmax bulk and SUV peak as well as an early treatment response at interim PET (i-PET) as a measure of chemosensitivity using ΔSUVmax may have additional predictive value. We tested different models for risk prediction aiming at a dynamic risk tool in the era of evolving radiomic features in functional imaging. Methods: All patients within the PETRA database with newly diagnosed DLBCL, who were treated with R-CHOP and had available clinical data, baseline PET and i-PET scans were included. The optimal transformation of Dmax bulk, SUV peak and ΔSUV max was determined by choosing the best fitting Cox regression model with 3-year PFS as outcome, with highest R2 and lowest Akaike Information Criterion (AIC), while the cross-validated c-index was obtained as a measure for discrimination. Subsequently, risk models were developed using clinical, baseline PET and i-PET data. The best risk model was compared to the IMPI model and our subsequent ClinicalPET model, also incorporating radiomic features (MTV, IPI, age, SUV peak and D maxbulk) by determination of risk re-classification rates and by generating kaplan-meier (KM)-curves based on 60-30-10 PFS risk groups. Results: 1014 patients were included in the analyses. Adding i-PET reponse (ΔSUV max) to the IMPI model markedly improved outcome prediction (AIC 3177.44, c-index 0.72) and was superior to IMPI model alone (AIC 3247.09, c-index 0.68). By adding D maxbulk outcome prediction was further improved (AIC 3143.23, c-index 0.74), while SUV peak did not show significant impact on outcome (p=0.07). Compared to the IMPI and the ClinicalPET model, the new model combining baseline features (MTV, age and D maxbulk) with i-PET reponse (ΔSUV max) led to a sharper segregation of KM-curves with an improved rate of correct progression risk classification (22%; 95% confidence interval 12.1-31.1%). Conclusions: Adding i-PET reponse to baseline clinical and PET parameters optimizes risk classification in DLBCL enabling individualized risk assessment in early phase of frontline treatment and outperforms our previous IMPI model and ClinicalPET models.

The effect of 18F-FDG PET/CT findings on prognosis in patients with diffuse large B cell lymphoma

Aims: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), plays an important role in both staging at the time of diagnosis and follow-up of treatment response in lymphoma. Our aim was to investigate the effect of different quantitative metabolic parameters, which are not used in routine practice, on treatment response and overall survival (OS) in patients with diffuse large B-cell lymphoma.&#x0D; Methods: A total of 26 patients were included in our retrospective cohort study. Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV)(2.5-%41- PERCIST -aort) and total lesion glycolysis index (TLG) (2.5-%41- PERCIST-aort) effect of metabolic parameters on treatment response and OS was investigated.&#x0D; Results: Metabolic parameters did not predict treatment response, while TLGPERCIST (p=0.034), TLGAORT (p=0.040), MTV41 (p=0.040) and TLG41 (p=0.034) parameters were statistically significant for OS. Median OS (months) was statistically significant in TLGPERCIST groups (p=0.047). While the median OS (months) in the TLGPERCIST

Artificial Intelligence-Driven Single-Shot PET Image Artifact Detection and Disentanglement: Toward Routine Clinical Image Quality Assurance.

Medical imaging artifacts compromise image quality and quantitative analysis and might confound interpretation and misguide clinical decision-making. The present work envisions and demonstrates a new paradigm PET image Quality Assurance NETwork (PET-QA-NET) in which various image artifacts are detected and disentangled from images without prior knowledge of a standard of reference or ground truth for routine PET image quality assurance. The network was trained and evaluated using training/validation/testing data sets consisting of 669/100/100 artifact-free oncological 18 F-FDG PET/CT images and subsequently fine-tuned and evaluated on 384 (20% for fine-tuning) scans from 8 different PET centers. The developed DL model was quantitatively assessed using various image quality metrics calculated for 22 volumes of interest defined on each scan. In addition, 200 additional 18 F-FDG PET/CT scans (this time with artifacts), generated using both CT-based attenuation and scatter correction (routine PET) and PET-QA-NET, were blindly evaluated by 2 nuclear medicine physicians for the presence of artifacts, diagnostic confidence, image quality, and the number of lesions detected in different body regions. Across the volumes of interest of 100 patients, SUV MAE values of 0.13 ± 0.04, 0.24 ± 0.1, and 0.21 ± 0.06 were reached for SUV mean , SUV max , and SUV peak , respectively (no statistically significant difference). Qualitative assessment showed a general trend of improved image quality and diagnostic confidence and reduced image artifacts for PET-QA-NET compared with routine CT-based attenuation and scatter correction. We developed a highly effective and reliable quality assurance tool that can be embedded routinely to detect and correct for 18 F-FDG PET image artifacts in clinical setting with notably improved PET image quality and quantitative capabilities.

Synthesis and Bioevaluation of 2-Styrylquinoxaline Derivatives as Tau-PET Tracers.

This study focused on designing and evaluating Tau-PET tracers for noninvasive positron emission computed tomography (PET) imaging of neurofibrillary tangles (NFTs), a hallmark pathology of Alzheimer's disease (AD). The tracers were synthesized with a 2-styrylquinoxaline scaffold and varying lengths of FPEG chains. The compound [18F]15, which had two ethoxy units, showed high affinity for recombinant K18-Tau aggregates (Ki = 41.48 nM) and the highest selectivity versus Aβ1-42 aggregates (8.83-fold). In vitro autoradiography and fluorescent staining profiles further validated the binding of [18F]15 or 15 toward NFTs in brain sections from AD patients and Tau-transgenic mice. In normal ICR mice, [18F]15 exhibited an ideal initial brain uptake (11.21% ID/g at 2 min) and moderate washout ratio (2.29), and micro-PET studies in rats confirmed its ability to penetrate the blood-brain barrier with the peak SUV value of 1.94 in the cortex. These results suggest that [18F]15 has the potential to be developed into a useful Tau-PET tracer for early AD diagnosis and evaluation of anti-Tau therapeutics.

Variaciones en los parámetros cuantitativos y en la puntuación de la escala de Deauville aplicando diferentes algoritmos de reconstrucción en las imágenes PET/TC con [18F]FDG de pacientes con linfoma

Introduction and Objectives18F-FDG PET with the Deauville score (DS) is a unique semiquantitative method for lymphoma. However, type of standard uptake values (max, mean, and peak) reconstruction algorithms could affect DS. We compared the Bayesian Penalized Likelihood reconstruction algorithm (BPL) with Ordered Subsets Expectation Maximization (OSEM) on quantitative parameters and DS in lymphoma. We investigated the effect of the size of the lymph node on quantitative variation. Patients and MethodsRaw PET data of 255 lymphoma patients were reconstructed separately with Q.Clear (GE Healthcare), a BPL, and SharpIR (GE Healthcare), an OSEM algorithm. In both images, each patient's liver, mediastinal blood pool, and SUVs (SUVmax, SUVmean, and SUVpeak) of a total of 487 lesions selected from the patients were performed. DSmax, DSmean, and DSpeak were compared. ResultsIn our study, DS increased significantly with BPL (p<0.001), and the DS increased to 4-5 in 30 patients evaluated as 1-2-3 with OSEM. It was found that the quantitative values of the lymph nodes increased statistically with BPL (p<0.001), and the liver from the reference regions were significantly decreased (p<0.001). In addition, difference in lymph node was independently associated with size of lesion and was significantly more pronounced in small lesions (p<0.001). The effects of BPL algorithm were more pronounced in SUVmax than in SUVmean and SUVpeak. DS-mean and DS-peak scores were less changed by BPL than DS-max. ConclusionDifferent reconstruction algorithms in FDG PET/CT affect the quantitative evaluation. That variation may affect the change in DS in lymphoma patients, thus affecting patient management.

The variation of quantitative parameters and Deauville scores with different reconstruction algorithms in FDG PET/CT imaging of lymphoma patients

Introduction and objectives18F-FDG PET with the Deauville score (DS) is a unique semiquantitative method for lymphoma. However, type of standard uptake values (max, mean, and peak) reconstruction algorithms could affect DS. We compared the Bayesian Penalized Likelihood reconstruction algorithm (BPL) with Ordered Subsets Expectation Maximization (OSEM) on quantitative parameters and DS in lymphoma. We investigated the effect of the size of the lymph node on quantitative variation. Patients and methodsRaw PET data of 255 lymphoma patients were reconstructed separately with Q.Clear (GE Healthcare), a BPL, and SharpIR (GE Healthcare), an OSEM algorithm. In both images, each patient's liver, mediastinal blood pool, and SUVs (SUVmax, SUVmean, and SUVpeak) of a total of 487 lesions selected from the patients were performed. DSmax, DSmean, and DSpeak were compared. ResultsIn our study, DS increased significantly with BPL (p < 0.001), and the DS increased to 4–5 in thirty patients evaluated as 1−2–3 with OSEM. It was found that the quantitative values of the lymph nodes increased statistically with BPL (p < 0.001), and the liver from the reference regions were significantly decreased (p < 0.001). In addition, difference in lymph node was independently associated with size of lesion and was significantly more pronounced in small lesions (p < 0.001). The effects of BPL algorithm were more pronounced in SUVmax than in SUVmean and SUVpeak. DS-mean and DS-peak scores were less changed by BPL than DS-max. ConclusionDifferent reconstruction algorithms in FDG PET/CT affect the quantitative evaluation. That variation may affect the change in DS in lymphoma patients, thus affecting patient management.

Baseline metabolic tumour burden improves risk stratification in Hodgkin lymphoma: A Children's Oncology Group study.

The Children's Oncology Group AHOD0831 study used a positron emission tomography (PET) response-adapted approach in high-risk Hodgkin lymphoma, whereby slow early responders (SERs) received more intensive therapy than rapid early responders (RERs). We explored if baseline PET-based characteristics would improve risk stratification. Of 166 patients enrolled in the COG AHOD0831 study, 94 (57%) had baseline PET scans evaluable for quantitative analysis. For these patients, total body metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax ) and peak SUV (SUVpeak ) were obtained. MTV/TLG thresholds were an SUV of 2.5 (MTV2.5 /TLG2.5 ) and 40% of the tumour SUVmax (MTV40% /TLG40% ). TLG2.5 was associated with event-free survival (EFS) in the complete cohort (p= 0.04) and in RERs (p= 0.01), but not in SERs (p= 0.8). The Youden index cut-off for TLG2.5 was 1841. Four-year EFS was 92% for RER/TLG2.5 up to 1841, 60% for RER/TLG2.5 greater than 1841, 74% for SER/TLG2.5 up to 1841 and 79% for SER/TLG2.5 greater than 1841. Second EFS for RER/TLG2.5 up to 1841 was 100%. Thus, RERs with a low baseline TLG2.5 experienced excellent EFS with less intensive therapy, whereas RERs with a high baseline TLG2.5 experienced poor EFS. These findings suggest that patients with a high upfront tumour burden may benefit from intensified therapy, even if they achieve a RER.

Quantitative assessment of translocator protein (TSPO) in the non-human primate brain and clinical translation of [18F]LW223 as a TSPO-targeted PET radioligand

ObjectivesTranslocator protein 18 kDa (TSPO) positron emission tomography (PET) can be harnessed for the non-invasive detection of macrophage-driven inflammation. [18F]LW223, a newly reported TSPO PET tracer which was insensitive to rs6971 polymorphism, showed favorable performance characteristics in a recent imaging study involving a rat myocardial infarction model. To enable quantitative neuroimaging with [18F]LW223, we conducted kinetic analysis in the non-human primate (NHP) brain. Further, we sought to assess the utility of [18F]LW223-based TSPO imaging in a first-in-human study. MethodsRadiosynthesis of [18F]LW223 was accomplished on an automated module, whereas molar activities, stability in formulation, lipophilicity and unbound free fraction (fu) of the probe were measured. Brain penetration and target specificity of [18F]LW223 in NHPs were corroborated by PET-MR imaging under baseline and pre-blocking conditions using the validated TSPO inhibitor, (R)-PK11195, at doses ranging from 5 to 10 mg/kg. Kinetic modeling was performed using one-tissue compartment model (1TCM), two-tissue compartment model (2TCM) and Logan graphical analyses, using dynamic PET data acquisition, arterial blood collection and metabolic stability testing. Clinical PET scans were performed in two healthy volunteers (HVs). Regional brain standard uptake value ratio (SUVr) was assessed for different time intervals. Results[18F]LW223 was synthesized in non-decay corrected radiochemical yields (n.d.c. RCYs) of 33.3 ± 6.5% with molar activities ranging from 1.8 ± 0.7 Ci/µmol (n = 11). [18F]LW223 was stable in formulation for up to 4 h and LogD7.4 of 2.31 ± 0.13 (n = 6) and fu of 5.80 ± 1.42% (n = 6) were determined. [18F]LW223 exhibited good brain penetration in NHPs, with a peak SUV value of ca. 1.79 in the whole brain. Pre-treatment with (R)-PK11195 substantially accelerated the washout and attenuated the area under the time-activity curve, indicating in vivo specificity of [18F]LW223 towards TSPO. Kinetic modeling demonstrated that 2TCM was the most suitable model for [18F]LW223-based neuroimaging. Global transfer rate constants (K1) and total volumes of distribution (VT) were found to be 0.10 ± 0.01 mL/cm3/min and 2.30 ± 0.17 mL/cm3, respectively. Dynamic PET data analyses across distinct time windows revealed that the VT values were relatively stable after 60 min post-injection. In a preliminary clinical study with two healthy volunteers, [18F]LW223 exhibited good brain uptake and considerable tracer retention across all analyzed brain regions. Of note, an excellent correlation between SUVr with VT was obtained when assessing the time interval from 20 to 40 min post tracer injection (SUVr(20–40 min), R2 = 0.94, p < 0.0001), suggesting this time window may be suitable to estimate specific binding to TSPO in human brain. ConclusionOur findings indicate that [18F]LW223 is suitable for quantitative TSPO-targeted PET imaging in higher species. Employing state-of-the-art kinetic modeling, we found that [18F]LW223 was effective in mapping TSPO throughout the NHP brain, with best model fits obtained from 2TCM and Logan graphical analyses. Overall, our results indicate that [18F]LW223 exhibits favorable tracer performance characteristics in higher species, and this novel imaging tool may hold promise to provide effective neuroinflammation imaging in patients with neurological disease.

Determination of diagnostic and predictive parameters for vertical mandibular invasion in patients with lower gingival squamous cell carcinoma: A retrospective study.

Vertical mandibular invasion of lower gingival squamous cell carcinoma (LGSCC) determines the method of resection, which significantly affects the patient's quality of life. Therefore, in mandibular invasion by LGSCC, it is extremely important to monitor progression, specifically whether invasion is limited to the cortical bone or has progressed to the bone marrow. This retrospective study aimed to identify the diagnostic and predictive parameters for mandibular invasion, particularly vertical invasion, to enable appropriate selection of the method of mandibular resection. Of the patients who underwent surgery for LGSCC between 2009 and 2017, 64 were eligible for participation in the study based on tissue microarrays (TMA) from surgical specimens. This study analyzed morphological features using computed tomography (CT), and metabolic characteristics using maximum standardized uptake value (SUVmax), peak value of SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Moreover, immunohistochemical analysis of proteins, including parathyroid hormone-related protein (PTHrP), interleukin-6 (IL-6), E-cadherin, and programmed cell death-1 ligand 1 (PD-L1), was performed. Statistical analysis was performed using univariate logistic regression analysis with the forward selection method. The present study showed that MTV (≥2.9 cm3) was an independent diagnostic and predictive factor for positivity of mandibular invasion. Additionally, TLG (≥53.9 bw/cm3) was an independent diagnostic and predictive factor for progression to bone marrow invasion. This study demonstrated that in addition to morphological imaging by CT, the volume-based parameters of MTV and TLG on fluorine-18 fluorodeoxyglucose positron emission tomography were important for predicting pathological mandibular invasion in patients with LGSCC. A more accurate preoperative diagnosis of vertical mandibular invasion would enable the selection of appropriate surgical procedure for mandibular resection.

PROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH

AbstractBackgroundThe need for a light stable 4R tau PET tracer for use in diverse tauopathies is widely appreciated. We aimed to assess the initial human imaging profile of [18F]APN‐1701 as such a tracer and to compare its imaging profile to the well‐established but light‐sensitive tracer [18F]‐APN‐1607 that can detect 4R aggregates as well as 3R and mixed 3R/4R aggregates. [18F]APN‐1607 has progressed to a multicenter Phase 2 clinical trial for Alzheimer’s disease (AD); therefore, prior imaging data with it was considered valuable for comparison.MethodOne cognitively normal (CN) subject (male, 73yo) and one AD subject (female, 58 yo), who had undergone prior amyloid profiling using [18F]florbetapir PET and subsequent imaging with [18F]APN‐1607 in a proof‐of‐concept study and a test‐retest study, respectively, participated in the current study. Dynamic imaging with [18F]APN‐1701 was performed over 180 min to obtain kinetic data.ResultOverall, for both subjects [18F]APN‐1701 generally matched [18F]APN‐1607 findings, i.e., peak SUV values reached similar levels. The CN subject, who was amyloid negative, had slight, uniform cortical [18F]‐APN‐1701 uptake and more substantial uptake in the pallidum, pons and midbrain. SUVr images for the AD subject showed retention in similar brain regions for both tau tracers with the same rank order of regional SUV/SUVr. Notably, for this subject [18F]APN‐1701 continued to accumulate up to the end of image acquisition.Conclusion[18F]APN‐1701 demonstrates cortical uptake generally similar to [18F]APN‐1607 but its slow kinetics are unfavorable for further development.

PROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH

AbstractBackgroundThe need for a light stable 4R tau PET tracer for use in diverse tauopathies is widely appreciated. We aimed to assess the initial human imaging profile of [18F]APN‐1701 as such a tracer and to compare its imaging profile to the well‐established but light‐sensitive tracer [18F]‐APN‐1607 that can detect 4R aggregates as well as 3R and mixed 3R/4R aggregates. [18F]APN‐1607 has progressed to a multicenter Phase 2 clinical trial for Alzheimer’s disease (AD); therefore, prior imaging data with it was considered valuable for comparison.MethodOne cognitively normal (CN) subject (male, 73yo) and one AD subject (female, 58 yo), who had undergone prior amyloid profiling using [18F]florbetapir PET and subsequent imaging with [18F]APN‐1607 in a proof‐of‐concept study and a test‐retest study, respectively, participated in the current study. Dynamic imaging with [18F]APN‐1701 was performed over 180 min to obtain kinetic data.ResultOverall, for both subjects [18F]APN‐1701 generally matched [18F]APN‐1607 findings, i.e., peak SUV values reached similar levels. The CN subject, who was amyloid negative, had slight, uniform cortical [18F]‐APN‐1701 uptake and more substantial uptake in the pallidum, pons and midbrain. SUVr images for the AD subject showed retention in similar brain regions for both tau tracers with the same rank order of regional SUV/SUVr. Notably, for this subject [18F]APN‐1701 continued to accumulate up to the end of image acquisition.Conclusion[18F]APN‐1701 demonstrates cortical uptake generally similar to [18F]APN‐1607 but its slow kinetics are unfavorable for further development.

The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study.

Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients’ characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions’ mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.

Impact of low injected activity on data driven respiratory gating for PET/CT imaging with continuous bed motion.

Data driven respiratory gating (DDG) in positron emission tomography (PET) imaging extracts respiratory waveforms from the acquired PET data obviating the need for dedicated external devices. DDG performance, however, degrades with decreasing detected number of coincidence counts. In this paper, we assess the clinical impact of reducing injected activity on a new DDG algorithm designed for PET data acquired with continuous bed motion (CBM_DDG) by evaluating CBM_DDG waveforms, tumor quantification, and physician's perception of motion blur in resultant images. Forty patients were imaged on a Siemens mCT scanner in CBM mode. Reduced injected activity was simulated by generating list mode datasets with 50% and 25% of the original data (100%). CBM_DDG waveforms were compared to that of the original data over the range between the aortic arch and the center of the right kidney using the Pearson correlation coefficient (PCC). Tumor quantification was assessed by comparing the maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) of reconstructed images from the various list mode datasets using elastic motion deblurring (EMDB) reconstruction. Perceived motion blur was assessed by three radiologists of one lesion per patient on a continuous scale from no motion blur (0) to significant motion blur (3). The mean PCC of the 50% and 25% dataset waveforms was 0.74 ± 0.18 and 0.59 ± 0.25, respectively. In comparison to the 100% datasets, the mean SUVmax increased by 2.25% (p = 0.11) for the 50% datasets and by 3.91% (p = 0.16) for the 25% datasets, while SUVpeak changes were within ±0.25%. Radiologist evaluations of motion blur showed negligible changes with average values of 0.21, 0.3, and 0.28 for the 100%, 50%, and 25% datasets. Decreased injected activities degrades the resultant CBM_DDG respiratory waveforms; however this decrease has minimal impact on quantification and perceived image motion blur.