Peak Standardized Uptake Value Research Articles

Kinetic Modeling of Brain [18-F]FDG Positron Emission Tomography Time Activity Curves with Input Function Recovery (IR) Method.

Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th-100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [18F]-fluorodeoxyglucose PET exams. Model validation involved 78 brain PET studies for which compartmental model (CM) analysis was feasible (reference (ref) + training sets). Recovered curves were compared with original curves using area under curve (AUC), max peak standardized uptake value (maxSUV). CM parameters (ref + training sets) and fractional uptake rate (FUR) (all sets) were computed. Original and recovered curves from the ref set had comparable AUC (d = 0.02, not significant (NS)), maxSUV (d = 0.05, NS) and comparable brain CM results (NS). Recovered curves from the training set were different from the original according to maxSUV (d = 3) and biologically plausible according to the max theoretical K1 (53//56). Brain CM results were different in the training set (p < 0.05 for all CM parameters and brain regions) but not in the ref set. FUR showed reductions similarly in the recovered curves of the training and test sets compared to the original curves (p < 0.05 for all regions for both sets). The IR method successfully recovered the plasma inputs of poor quality, rescuing cases otherwise excluded from the kinetic modeling results. The validation approach proved useful and can be applied to different tracers and metabolic conditions.

Evaluation of Three Imaging Methods to Quantify Key Events in Pelvic Bone Metastasis.

The purpose of this study is to compare turbo spin echo diffusion-weighted images in radial trajectory (BLADE DWI) with multi-shot echoplanar imaging (RESOLVE DWI) for imaging the metastatic lesion in the pelvic bone to find a correlation between ADC values and standardized uptake values (SUVs) of FDG uptake in PET/CT. The study also seeks to compare the values of metastatic lesions with those of benign bone lesions, specifically red marrow hyperplasia. The retrospective IRB-approved study included patients with bone metastasis and red marrow hyperplasia in the pelvic bone who underwent 3.0 T MRI with BLADE/RESOLVE DWI sequences and F-18 FDG PET/CT within one month. BVC (best value comparator) was used in determining the nature of bone lesions. Apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were measured by a radiologist and a nuclear medicine physician. MRI image quality was graded with a Likert scale regarding the visualization of the sacroiliac joint, sacral neural foramen, hamstring tendon at ischial tuberosity, and tumor border. Signal-to-noise ratio (SNR) and imaging time were compared between the two DWIs. Mean, peak, and maximum SUVs between metastatic and benign red marrow lesions were compared. SUVs and ADC values were compared. AUROC analyses and cut-off values were obtained for each parameter. Mann-Whitney U, Spearman's rho, and Kolmogorov-Smirnov tests were applied using SPSS. The final study group included 58 bone lesions (19 patients (male: female = 6:13, age 52.5 ± 9.6, forty-four (75.9%) bone metastasis, fourteen (24.1%) benign red marrow hyperplasia). ADCs from BLADE and RESOLVE were significantly higher in bone metastasis than red marrow hyperplasia. BLADE showed higher ADC values, higher anatomical scores, and higher SNR than RESOLVE DWI (p < 0.05). Imaging times were longer for BLADE than RESOLVE (6 min 3 s vs. 3 min 47 s, p < 0.05). There was a poor correlation between ADC values and SUVs (correlation coefficient from 0.04 to 0.31). The AUROC values of BLADE and RESOLVE MRI ranged from 0.892~0.995. Those of PET ranged from 0.877~0.895. The cut-off ADC values between the bone metastasis and red marrow hyperplasia were 355.0, 686.5, 531.0 for BLADE min, max, and average, respectively, and 112.5, 737.0, 273.0 for RESOLVE min, max, and average, respectively. The cut-off SUV values were 1.84, 5.01, and 3.81 for mean, peak, and max values, respectively (p < 0.05). Compared with RESOLVE DWI, BLADE DWI showed improved image quality of pelvic bone MRI in the aspect of anatomical depiction and SNR, higher ADC values, albeit longer imaging time. BLADE and RESOLVE could differentiate bone metastasis and red marrow hyperplasia with quantifiable cut-off values. Further study is necessary to evaluate the discrepancy between the quantifiers between PET and MRI.

Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT.

We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5-87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in early-phase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13-36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80-13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41-19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00-14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16-21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874-0.956] vs. 0.815 [0.732-0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816-0.967) in candidates for endoscopic papillectomy. Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Predictive value of 2-deoxy-2-fluorine-18-fluoro-D-glucose positron emission tomography/computed tomography parameters for MYCN amplification in high-risk neuroblastoma

ObjectivesTo investigate the predictive value of 2-deoxy-2-fluorine-18-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters for MYCN amplification in high-risk neuroblastoma (HR-NB). Materials and methodsA retrospective analysis was performed by reviewing 68 HR-NB patients who underwent MYCN testing and 18F-FDG PET/CT imaging at our hospital between January 2018 and December 2019. Based on the results of MYCN testing, patients were categorized into either the MYCN-amplified (MNA) or MYCN non-amplified (MYCN-NA) group. The 18F-FDG PET/CT parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), tumor metabolic volume (MTV), total lesion glycolysis (TLG), coefficient of variation (COV), and areas under the curve of cumulative SUV-volume histogram index (AUC-CSH index) were evaluated. Independent predictors were identified through univariate and multivariate logistic regression analyses, and their diagnostic performance was evaluated using the receiver-operating characteristic (ROC) curve. ResultsUnivariate logistic regression analysis revealed that SUVpeak was significantly associated with MYCN amplification. Multivariate logistic regression analysis showed that SUVpeak was an independent predictor of MYCN amplification in HR-NB [Odds ratio (OR) = 0.673, 95 % confidence interval (95 % CI): 0.494–0.917, P = 0.012]. ROC curve analysis demonstrated that the predictive model including SUVpeak had higher diagnostic performance [area under the curve (AUC): 0.790, 95 % CI: 0.677–0.881, sensitivity: 0.861, specificity: 0.591, positive predictive value (PPV): 0.820, negative predictive value (NPV): 0.722] compared to using SUVpeak alone (AUC: 0.640, 95 % CI: 0.514–0.752, sensitivity: 0.630, specificity: 0.682, PPV: 0.806, NPV: 0.469). ConclusionSUVpeak can predict the MYCN amplification in HR-NB patients. The predictive model constructed by combining SUVpeak and age can distinguish MYCN status in HR-NB non-invasively with superior efficacy compared to using SUVpeak alone.

Baseline 18f-Fluorodeoxyglucose PET/CT Radiomics Predicts Outcome in Newly Diagnosed Intravascular Large B-Cell Lymphoma

[Introduction] Treatment outcomes of intravascular large B-cell lymphoma (IVLBCL), a rare subtype of extra-nodal diffuse large B-cell lymphoma (DLBCL), have dramatically improved in recent years. However, prognostic factors for IVLBCL are largely unknown. Several studies have explored the potential of the baseline 18F-fluorodeoxyglucose (FDG) PET/CT radiomics features to identify patients with poor prognosis. For example, metabolic tumor volume (MTV) reflects the FDG-avid tumor burden, and the maximum distance between the largest lesion and any other lesion quantifies the dissemination of the tumor, and both factors are inversely related to overall survival (OS) and progression-survival (PFS) in DLBCL. In this study, we explored prognostic impact of FDG PET/CT radiomics features in newly diagnosed IVLBCL. [Methods] We retrospectively evaluated patients with histopathologically proven newly diagnosed IVLBCL according to the 2008 World Health Organization criteria between January 2010 through February 2022 from hospitals participating in the North Japan Hematology Study Group (NJHSG). Quantitative analysis of all FDG PET/CT was performed using Metavol (Hokkaido University, Sapporo, Japan), with exclusion of physiological accumulation. MTV was defined as the volume of lymphoma lesions visualized on PET/CT scans with standardized uptake value (SUV) peaks greater than or equal to hepatic SUV peak. To quantify the dissemination of the tumor, we calculated the number of the body areas (head-neck, chest, abdomen, upper-extremities, lower-extremities) having BM lesions with a higher SUV peak than liver SUV peak. Patients with BM lesions spread across 4-5 areas were defined as cases having widely disseminated lesions (WDL). Progression-free survival (PFS) was defined as the time from the start of treatment to the first of progression, relapse, or death from any cause. Patients undergoing upfront autologous stem-cell transplantation (auto-SCT) were censored at the time of transplantation. [Results] We identified fifty-two IVLBCL patients (age 30-89 years, median 65 years; 57.7% male) who performed FDG PET/CT at diagnosis. Twenty-eight patients (54.9%) had poor performance status (ECOG PS ≥2), and 49 patients (94.2%) showed stage III-IV. Forty-nine patients (94.2%) had 2 or more extranodal involvement. Elevated serum LDH level was observed in 49 cases (94.2%) (median, 623.5 IU/L; range, 147-4907 IU/L). The median serum levels of soluble IL-2 receptor (sIL-2R), ferritin, and C-reactive protein (CRP) were 4496.5 IU/mL (range, 321-19900 IU/mL), 655.15 ng/mL (range, 50-6657 ng/mL), and 6.905 mg/dL (range, 0.11-25.86 mg/dL), respectively. The median MTV was 415.527 cm 3 (range, 0-3000 cm 3). ROC analysis revealed that the cutoff value of the MTV &amp;gt; 388 cm 3 could predict progression events within 2 years. Area under curve was 0.71 (95% CI: 0.564-0.857). Twenty-nine patients (55.8%) were classified as having MTV &amp;gt; 388 cm 3 (high MTV). Twenty-three patients (44.2%) had WDL. Fifty-one (98.1%) patients received chemotherapy, all of which was rituximab-containing regimen. Three patients (5.8%) received upfront auto-SCT. Median follow-up duration was 48.8 months (range, 5.8-140.5 months) in survivors. Age, LDH level, number of extranodal lesions, clinical stage, and PS did not affect OS and PFS. Although the high MTV and WDL did not significantly affect OS ( P = 0.095, P = 0.173, respectively; Log-rank), these findings did correlate significantly with poor PFS ( P = 0.011, P = 0.042, respectively; Log-rank). Thus, we defined a high MTV or a WDL as poor PET findings. Thirty-two patients had poor PET findings. Importantly, patients with poor PET findings showed significantly poor OS and PFS compared to patients without (2-year OS: 71.2% vs. 93.3%, P = 0.015, 2-year PFS: 45.5% vs. 93.8%, P = 0.001; Log-rank, Fig. 1, 2). [Conclusion] This is the largest study to assess prognostic impact of FDG PET/CT radiomics features on newly diagnosed IVLBCL. Poor PET findings were significantly correlated with worse OS and PFS.

Synthesis and evaluation of a novel PET ligand, a GSK’963 analog, aiming at autoradiography and imaging of the receptor interacting protein kinase 1 in the brain

BackgroundReceptor interacting protein kinase 1 (RIPK1) is a serine/threonine kinase, which regulates programmed cell death and inflammation. Recently, the involvement of RIPK1 in the pathophysiology of Alzheimer’s disease (AD) has been reported; RIPK1 is involved in microglia’s phenotypic transition to their dysfunctional states, and it is highly expressed in the neurons and microglia in the postmortem brains in AD patients. They prompt neurodegeneration leading to accumulations of pathological proteins in AD. Therefore, regulation of RIPK1 could be a potential therapeutic target for the treatment of AD, and in vivo imaging of RIPK1 may become a useful modality in studies of drug discovery and pathophysiology of AD. The purpose of this study was to develop a suitable radioligand for positron emission tomography (PET) imaging of RIPK1.Results(S)-2,2-dimethyl-1-(5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)propan-1-one (GSK’963) has a high affinity, selectivity for RIPK1, and favorable physiochemical properties based on its chemical structure. In this study, since 11C-labeling (half-life: 20.4 min) GSK’963 retaining its structure requiring the Grignard reaction of tert-butylmagnesium halides and [11C]carbon dioxide was anticipated to give a low yield, we decided instead to 11C-label a GSK’963 analog ((S)-2,2-dimethyl-1-(5-(m-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)propan-1-one, GG502), which has a high RIPK1 inhibitory activity equivalent to that of the original compound GSK’963. Thus, we successfully 11C-labeled GG502 using a Pd-mediated cross-coupling reaction in favorable yields (3.6 ± 1.9%) and radiochemical purities (> 96%), and molar activity (47–115 GBq/μmol). On autoradiography, radioactivity accumulation was observed for [11C]GG502 and decreased by non-radioactive GG502 in the mouse spleen and human brain, indicating the possibility of specific binding of this ligand to RIPK1. On brain PET imaging in a rhesus monkey, [11C]GG502 showed a good brain permeability (peak standardized uptake value (SUV) ~3.0), although there was no clear evidence of specific binding of [11C]GG502. On brain PET imaging in acute inflammation model rats, [11C]GG502 also showed a good brain permeability, and no significant increased uptake was observed in the lipopolysaccharide-treated side of striatum. On metabolite analysis in rats at 30 min after administration of [11C]GG502, ~55% and ~10% of radioactivity was from unmetabolized [11C]GG502 in the brain and the plasma, respectively.ConclusionsWe synthesized and evaluated a 11C-labeled PET ligand based on the methylated analog of GSK’963 for imaging of RIPK1 in the brain. Although in autoradiography of the resulting [11C]GG502 indicated the possibility of specific binding, the actual PET imaging failed to detect any evidence of specific binding to RIPK1 despite its good brain permeability. Further development of radioligands with a higher binding affinity for RIPK1 in vivo and more stable metabolite profiles compared with the current compound may be required.

Valor pronóstico de los parámetros metabólicos volumétricos del tumor primario y ganglios linfáticos en el PET/TC pretratamiento en el carcinoma nasofaríngeo

BackgroundThe aim of this study was to evaluate the prognostic significance of volumetric metabolic parameters of pre-treatment PET/CT along with clinical characteristics in patients with non-metastatic nasopharyngeal carcinoma. Material and methodsSeventy-nine patients with nasopharyngeal carcinoma underwent F18-FDG PET/CT for pretreatment evaluation and included in this study. The patient features (patient age, tumor histopathology, T and N stage, size of primary tumor and the largest cervical lymph node) and PET parameters were analyzed: maximum, mean and peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumor and largest cervical lymph node. After treatment, patients were evaluated for disease progression and mortality. Survival analysis for progression-free survival (PFS) and over-all survival (OS) was performed with Kaplan–Meier method using PET findings and clinical characteristics. ResultsThe median follow-up duration was 29.7 months (range 3–125 months). Among clinical characteristics, no parameters had significance association for PFS. Primary tumor-MTV and cervical lymphnode-MTV were independent prognostic factors for PFS (p = 0.025 and p = 0.004, respectively). Patients with primary tumor-MTV > 19.4 and patients with lymph node-MTV > 3.4 had shorter PFS. For OS, age and the size of the lymph node were independent prognostic factor (p = 0.031 and p = 0.029). Patients with age over 54 years and patients with lymph node size > 1 cm were associated with decreased OS. ConclusionPrimary tumor-MTV and lymph node-MTV on pre-treatment PET/CT are significant prognostic factors for long-term PFS in non-metastatic nasopharyngeal carcinoma. We consider that measuring MTV as volume-based metabolic parameter on pretreatment PET/CT may contribute decision of treatment intensity and individualized risk stratification and may improve long-term PFS. Additionally, age and the size of lymph node are independent prognostic factors for mortality.

Performance of 18F-FDG PET/MR on TNM staging of pancreatic cancer compared with 18F-FDG PET/CT: A retrospective cohort study

PurposeThis study aimed to evaluate the TNM staging accuracy of 18F-FDG PET/MR compared with 18F-FDG PET/CT in patients with pancreatic cancer. Materials and methodsIn this retrospective cohort study, a total of 88 patients (53 men, 35 women, mean age 64.56±10.77 years) with pathologically confirmed pancreatic cancer who underwent 18F-FDG PET/CT and 18F-FDG PET/MR successively on the same day were enrolled. The maximal and peak standardized uptake values (SUVmax and SUVpeak) of pancreatic cancer lesions on PET/MR and PET/CT imaging were measured respectively. According to the 8th edition AJCC staging system of pancreatic adenocarcinoma, two experienced readers reviewed and assessed the PET/CT and PET/MR images independently for TNM staging. Using the diagnosis of enhanced CT, histopathological diagnosis and/or the clinical follow-up as the reference, the diagnostic performance of PET/CT and PET/MR were compared using the McNemar test. ResultsCompared with 18F-FDG PET/CT (63.64%), 18F-FDG PET/MR (85.23%) exhibited significantly higher diagnostic accuracy of T staging (P<0.05). In N staging, the diagnostic accuracy of PET/MR (81.4%) was higher than that of PET/CT (74.42%) but the difference was not statistically significant. In M staging, no significant difference was found between the diagnostic performance of PET/MR (96.59%) and PET/CT (92.05%). However, PET/MR detected more liver metastases in 11/18 patients and the clinical staging was upstaged in four patients compared to PET/CT. Both SUVmax and SUVpeak of pancreatic tumors showed strong correlations between PET/MR and PET/CT imaging (r=0.901 and 0.923, respectively; P<0.05). ConclusionsCompared with 18FFDG PET/CT, 18FFDG PET/MR showed better performance in the TNM staging of pancreatic cancer, especially in T staging and detection of liver metastases.

Prognostic value of primary tumor and lymph node volumetric metabolic parameters at pre-treatment F-18 FDG PET/CT in nasopharyngeal carcinoma

BackgroundThe aim of this study was to evaluate the prognostic significance of volumetric metabolic parameters of pre-treatment PET/CT along with clinical characteristics in patients with non-metastatic nasopharyngeal carcinoma. Material and methodsSeventy-nine patients with nasopharyngeal carcinoma underwent F18- FDG PET/CT for pretreatment evaluation and included in this study. The patient features (patient age, tumor histopathology, T and N stage, size of primary tumor and the largest cervical lymph node) and PET parameters were analyzed: maximum, mean and peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumor and largest cervical lymph node. After treatment, patients were evaluated for disease progression and mortality. Survival analysis for progression-free survival (PFS) and over-all survival (OS) was performed with Kaplan–Meier method using PET findings and clinical characteristics. ResultsThe median follow-up duration was 29.7 months (range 3–125 months). Among clinical characteristics, no parameters had significance association for PFS. Primary tumor-MTV and cervical lymph node-MTV were independent prognostic factors for PFS (p = 0.025 and p = 0.004, respectively).Patients with primary tumor-MTV >19.4 and patients with lymph node-MTV>3.4 had shorter PFS. For OS, age and the size of the lymph node were independent prognostic factor (p = 0.031 and p = 0.029).Patients with age over 54 years and patients with lymph node size >1 cm were associated with decreased OS. ConclusionPrimary tumor-MTV and lymph node-MTV on pre-treatment PET/CT are significant prognostic factors for long-term PFS in non-metastatic nasopharyngeal carcinoma.We consider that measuring MTV as volume-based metabolic parameter on pretreatment PET/CT may contribute decision of treatment intensity and individualized risk stratification and may improve long-term PFS. Additionally, age and the size of lymph node are independent prognostic factors for mortality.

Lymphoma-Sink Effect in Marginal Zone Lymphoma Based on CXCR4-Targeted Molecular Imaging

PurposeRecent studies investigating a tumor-sink effect in solid tumors reported on decreasing uptake in normal organs in patients with higher tumor burden. This phenomenon, however, has not been evaluated yet for theranostic radiotracers applied to hematological neoplasms. As such, we aimed to determine a potential “lymphoma-sink effect” in patients with marginal zone lymphoma (MZL) imaged with C-X-C motif chemokine receptor (CXCR) 4-directed PET/CTs.ProceduresWe retrospectively analyzed 73 patients with MZL who underwent CXCR4-directed [68Ga]Ga-PentixaFor PET/CT. Normal unaffected organ uptake (heart, liver, spleen, bone marrow, kidneys) was quantified using volumes of interests (VOIs) and mean standardized uptake values (SUVmean) were derived. MZL manifestations were also segmented to determine the maximum and peak standardized uptake values SUV (SUVmax/peak) and volumetric parameters, including lymphoma volume (LV), and fractional lymphoma activity (FLA, defined as LV*SUVmean of lymphoma burden). This approach resulted in 666 VOIs to capture the entire MZL manifestation load. We used Spearman’s rank correlations to determine associations between organ uptake and CXCR4-expressing lymphoma lesions.ResultsWe recorded the following median SUVmean in normal organs: heart, 1.82 (range, 0.78–4.11); liver, 1.35 (range, 0.72–2.99); bone marrow, 2.36 (range, 1.12–4.83); kidneys, 3.04 (range, 2.01–6.37); spleen, 5.79 (range, 2.07–10.5). No relevant associations between organ radiotracer uptake and MZL manifestation were observed, neither for SUVmax (ρ ≤ 0.21, P ≥ 0.07), SUVpeak (ρ ≤ 0.20, P ≥ 0.09), LV (ρ ≤ 0.13, P ≥ 0.27), nor FLA (ρ ≤ 0.15, P ≥ 0.33).ConclusionsInvestigating a lymphoma-sink effect in patients with hematological neoplasms, we observed no relevant associations between lymphoma burden and uptake in normal organs. Those observations may have therapeutic implications, e.g., for “cold” SDF1-pathway disrupting or “hot,” CXCR4-directed radiolabeled drugs, as with higher lymphoma load, normal organ uptake seems to remain stable.

PET/CT reading for relapse in non-small cell lung cancer after chemoradiotherapy in the PET-Plan trial cohort

BackgroundCurrent studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([18F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial.MethodsThis retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [18F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease.ResultsOverall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97).ConclusionVisual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Baseline and early digital [ 18 F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients: a pilot study.

In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [ 18 F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected. Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. Both multiparametric MRI and [ 18 F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.

Evaluation of Semiautomatic and Deep Learning-Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.

Baseline PET radiomics outperforms the IPI risk score for prediction of outcome in diffuse large B-cell lymphoma

AbstractThe objective of this study is to externally validate the clinical positron emission tomography (PET) model developed in the HOVON-84 trial and to compare the model performance of our clinical PET model using the international prognostic index (IPI). In total, 1195 patients with diffuse large B-cell lymphoma (DLBCL) were included in the study. Data of 887 patients from 6 studies were used as external validation data sets. The primary outcomes were 2-year progression-free survival (PFS) and 2-year time to progression (TTP). The metabolic tumor volume (MTV), maximum distance between the largest lesion and another lesion (Dmaxbulk), and peak standardized uptake value (SUVpeak) were extracted. The predictive values of the IPI and clinical PET model (MTV, Dmaxbulk, SUVpeak, performance status, and age) were tested. Model performance was assessed using the area under the curve (AUC), and diagnostic performance, using the positive predictive value (PPV). The IPI yielded an AUC of 0.62. The clinical PET model yielded a significantly higher AUC of 0.71 (P < .001). Patients with high-risk IPI had a 2-year PFS of 61.4% vs 51.9% for those with high-risk clinical PET, with an increase in PPV from 35.5% to 49.1%, respectively. A total of 66.4% of patients with high-risk IPI were free from progression or relapse vs 55.5% of patients with high-risk clinical PET scores, with an increased PPV from 33.7% to 44.6%, respectively. The clinical PET model remained predictive of outcome in 6 independent first-line DLBCL studies, and had higher model performance than the currently used IPI in all studies.

Abstract 3576: Molecular imaging of CD8 infiltration following combination immunotherapy in preclinical glioblastoma

Abstract Background: Novel immune-promoting therapeutics for glioblastoma multiforme (GBM), such as oncolytic herpes simplex viruses (oHSV) and immune checkpoint inhibitors (ICI), have the potential to improve overall survival and lead to long-term remission, however their clinical benefit remains inconsistent. Under standard of care imaging, assessment of immunotherapeutic response can be limited by apparent radiological tumor progression associated with treatment-induced inflammation and immune infiltration. This has led to a need for better understanding of immune cell dynamics and immunotherapy response in GBM. The objective of this study is to evaluate changes in CD8+ infiltration and its relation to therapy response, through positron emission tomography (PET) imaging, in preclinical GBM. Methods: GSC005-luc orthotopic GBM models (n= 40) were treated with saline, M002 oHSV, anti-PD1 or combination immunotherapy following three weeks of tumor growth. One-week post-treatment, [89Zr]-CD8 PET imaging was performed and biologically validated through ex vivo PET, autoradiography and staining for H&amp;E and CD8 immunohistochemistry (IHC). Further, longitudinal changes in CD8 infiltration were evaluated via [89Zr]-CD8 PET imaging one- and three-weeks post-immunotherapy with responses monitored every three days via bioluminescence imaging (BLI). Statistical analysis involved one-way ANOVA and unpaired T-test, with p&amp;lt;0.05 considered significant. Results: Linear correlations were seen between in vivo PET signal and ex vivo uptake (r=0.61, p&amp;lt;0.01), autoradiography (r=0.46, p&amp;lt;0.01), and IHC tumor CD8+ cell density (r=0.55, p&amp;lt;0.01) one-week post-treatment. Immunotherapy efficacy, defined by decreased BLI signal, resembled clinical findings as only a subset of mice exhibited long-term positive response measured by BLI signal decrease (n=9/24). Response classification revealed increased CD8+ cell tumor localization, as measured by peak standardized uptake value (SUVpeak) tumor to background ratio (TBR), in non-responders (p&amp;lt;0.01) and decreased heterogeneity in signal distribution in responders (p&amp;lt;0.05) relative to controls early in the course of therapy. Conclusions: Early CD8 infiltration and uptake distribution from CD8-PET imaging provides potential imaging metrics of therapeutic response to oHSV immunotherapy in GBM. Development of these immune-focused imaging approaches for the assessment of positive immunotherapeutic effects in GBM is beneficial for the better understanding of immune cell dynamics and their relation to clinical outcomes. Citation Format: Carlos A. Gallegos, Yun Lu, Alessandro Mascioni, Fang Jia, Jennifer C. Clements, Patrick N. Song, Shannon E. Lynch, Jason M. Warram, James M. Markert, Anna Sorace. Molecular imaging of CD8 infiltration following combination immunotherapy in preclinical glioblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3576.

Multiparameter diagnostic model based on 18F-FDG PET metabolic parameters and clinical variables can differentiate nonmetastatic gallbladder cancer and cholecystitis

ObjectiveTo evaluate the diagnostic value of a multiparameter model based on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters and clinical variables in differentiating nonmetastatic gallbladder cancer (GBC) from cholecystitis.Patients and methodsIn total, 122 patients (88 GBC nonmetastatic patients and 34 cholecystitis patients) with gallbladder space-occupying lesions who underwent 18F-FDG PET/CT were included. All patients received surgery and pathology, and baseline characteristics and clinical data were also collected. The metabolic parameters of 18F-FDG PET, including SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), SUVpeak (peak standard uptake value), MTV (metabolic tumour volume), TLG (total lesion glycolysis) and SUVR (tumour-to-normal liver standard uptake value ratio), were evaluated. The differential diagnostic efficacy of each independent parameter and multiparameter combination model was evaluated using the receiver operating characteristic (ROC) curve. The improvement in diagnostic efficacy using a combination of the above multiple parameters was evaluated by integrated discriminatory improvement (IDI), net reclassification improvement (NRI) and bootstrap test. Decision curve analysis (DCA) was used to evaluate clinical efficacy.ResultsThe ROC curve showed that SUVR had the highest diagnostic ability among the 18F-FDG PET metabolic parameters (area under the curve [AUC] = 0.698; sensitivity = 0.341; specificity = 0.971; positive predictive value [PPV] = 0.968; negative predictive value [NPV] = 0.363). The combined diagnostic model of cholecystolithiasis, fever, CEA > 5 ng/ml and SUVR showed an AUC of 0.899 (sensitivity = 0.909, specificity = 0.735, PPV = 0.899, NPV = 0.758). The diagnostic efficiency of the model was improved significantly compared with SUVR. The clinical efficacy of the model was confirmed by DCA.ConclusionsThe multiparameter diagnostic model composed of 18F-FDG PET metabolic parameters (SUVR) and clinical variables, including patient signs (fever), medical history (cholecystolithiasis) and laboratory examination (CEA > 5 ng/ml), has good diagnostic efficacy in the differential diagnosis of nonmetastatic GBC and cholecystitis.

Clinical Analysis of Pulmonary Lymphoma

To study the clinical, imaging, and pathological features of pulmonary lymphoma. Patients with pulmonary lymphoma diagnosed by lung biopsy in Zhongda Hospital Affiliated to Southeast University from November 2013 to December 2020 were collected and divided into secondary pulmonary lymphoma (SPL) group and primary pulmonary lymphoma (PPL) group according to the primary site of lymphoma. The clinical characteristics, stages, imaging features, diagnostic methods and pathological types of the two groups were analyzed. A total of 22 patients were included, 10 cases were PPL and 12 cases were SPL. The main symptoms of the two groups were cough, dyspnea and chest pain. The proportion of stage III/IV patients and international prognostic index (IPI) in SPL group were significantly higher than those in PPL group (P<0.05). Chest high-resolution computed tomography (HRCT) mainly showed masses, nodules and consolidation in both groups. The proportions of single mass and air bronchial sign in PPL group were significantly higher than those in SPL group, while the proportions of multiple nodules, mediastinal/hilar lymphadenopathy and pleural effusion were significantly lower (P<0.05). The max standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in PPL group were lower than those in SPL group, but the differences were not statistically significant (P>0.05). In PPL group, 8 cases were diagnosed by transbronchial lung biopsy (TBLB) and 2 cases by percutaneous lung puncture. In SPL group, 4 cases were diagnosed by TBLB, 7 cases by percutaneous lung puncture, and 1 case by surgery. 95.5% patients were diagnosed by non-surgical methods. The main pathological type of PPL was mucosa-associated lymphoid tissue (MALT) lymphoma, while that of SPL was diffuse large B-cell lymphoma (P<0.05). The clinical symptoms of pulmonary lymphoma are nonspecific, but the chest HRCT has characteristic manifestations, which can also help to distinguish between SPL and PPL. 18F-FDG PET/CT is also a potential method to distinguish between SPL and PPL. TBLB and percutaneous lung puncture biopsy are reliable methods for the diagnosis of lung lymphoma. The main pathological type of PPL is MALT lymphoma, while that of SPL is diffuse large B-cell lymphoma.

Prognostic impact of 18F-FDG PET/CT in pathologic stage II invasive ductal carcinoma of the breast: re-illuminating the value of PET/CT in intermediate-risk breast cancer

BackgroundThe aim of this study is to investigate the impact of 18F-FDG PET/CT on prognosis of stage II invasive ductal carcinoma (IDC) of the breast primarily treated with surgery.MethodsThe clinical records of 297 consecutive IDC with preoperative PET/CT and pathologically staged II in surgery from 2013 to 2017 were retrospectively reviewed. The maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-liver ratio (TLR), and metabolic tumor volume (MTV) were measured. Association of clinicopathologic factors (age, T stage, N stage, AJCC pathologic stage of IIA or IIB, pathologic prognostic stage, grade, hormonal receptor status, HER2 status, Ki-67, and adjuvant therapy) and PET parameters with DFS was assessed using the Cox proportional hazards model.ResultsThere were 35 recurrences and 10 deaths at a median follow-up of 49 months (range 0.8 ~ 87.3). All PET parameters were significantly associated with DFS in univariate analysis but in multivariate analysis, SUVpeak was the only factor significantly associated with DFS (hazard ratio 2.58, 95% confidence interval 1.29–5.15, P = 0.007). In cohorts with higher values of SUVpeak or TLR, patients who received adjuvant chemotherapy had significantly superior DFS.ConclusionMetabolic parameters derived from preoperative PET/CT was significantly associated with recurrence in stage II IDC primarily treated with surgery. PET/CT can be a powerful prognostic tool in conjunction with novel staging systems and current biomarkers for patients undergoing contemporary therapy. Our results urge to reconsider the currently underestimated value of PET/CT confined to diagnostic aspect and to newly recognize its prognostic impact in these intermediate-risk breast cancer.

18 F-FDG PET/CT parameters for prediction of response to neoadjuvant therapy and prognosis in rectal cancer.

This study aims to investigate the role of F-18 fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) parameters in the prediction of treatment response and the prognosis in locally advanced rectal cancer. We investigated the relationship of 18F-FDG PET/CT parameters [rectal metabolic tumor volume (MTV), rectal total lesion glycolysis (TLG), rectal standard uptake value (SUV) max, rectal highest peak SUV, lymph node MTV, lymph node TLG, lymph node highest peak SUV] with the pathological response and disease-free survival (DFS) in 60 patients who received neoadjuvant therapy for a diagnosis of locally advanced rectal cancer. Patients with a total score of 0 were assigned to the low-risk group, patients with a score of 1 were assigned to the intermediate-risk group and patients with a score of 2 were assigned to the high-risk group. The multivariate analysis revealed that, from baseline PET CT parameters, lymph node highest peak SUV strongly predicted the pathological response at a cutoff value of 2.23. DFS was predicted by the lymph node highest peak SUV at a cutoff value of 3.13 and by the MTV value at a cutoff value of 27 cm 3 . The risk scoring performed with regard to rectal MTV and lymph node highest peak SUV values determined a median DFS of 19 months in patients with a risk score of 2, whereas the median DFS was not reached in patients with risk scores of 0 and 1 (P < 0.001). This study determined that rectal MTV and lymph node highest peak SUV predicted the response to neoadjuvant therapy and DFS.

External Validation Shows That Baseline PET Radiomics Outperform the IPI Risk Score for Prediction of Outcome in DLBCL

Introduction Up to one-third of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients relapse or fail to achieve complete remission following first-line treatment. Adding PET radiomics features to currently used clinical predictors may improve the identification of poor prognosis patients. The objective of this study was to externally validate the radiomics model developed in the HOVON-84 trial (Eertink et al, EJNMMI 2021) using datasets from 6 other DLBCL research studies within the PETRA database. Methods 1195 newly diagnosed DLBCL patients with baseline 18F-FDG PET/CT scans with 2 years follow up in 7 studies in the PETRA database (https://petralymphoma.org) were included. 308 patients from the HOVON 84 were used as test set previously described. 887 patients from 6 studies in the PETRA database were used as external validation datasets. Primary outcome measures were 2-year progression free survival (PFS) and 2-year time to progression (TTP). Lesions were delineated using a fully automated preselection of 18F-FDG avid structures defined by a standardized Uptake Value (SUV) ≥ 4.0 and volume >3mL. Missed lesions were manually added and non-tumor regions were removed using the ACCURATE tool. Metabolic tumor volume (MTV), the maximum distance between the largest lesion and any other lesion (DmaxBulk) and the peak standardized uptake value (SUVpeak) were extracted for all patients. We tested the predictive value of the currently used international prognostic index (IPI) score and the radiomics model developed in the HOVON-84 trial, which included MTV, DmaxBulk, SUVpeak, WHO performance status and age. Model performance was assessed using the receiver-operator-characteristics area under the curve (AUC). To allow comparison of the continuous radiomics model with individual predicted probabilities per patient with the categorical IPI risk score, the high-risk group for the radiomics model was set as equal the size of the high-risk IPI group. Diagnostic performance was assessed using the positive predictive value (PPV). Differences between model performances of prediction models, expressed as AUC, were assessed with the two-sided DeLong test. Results Using 2-year PFS as outcome, the IPI model yielded an AUC of 0.62 using all 1195 patients (Table 1). Within the 6 external datasets, the AUC of the IPI model ranged from 0.51 for the SAKK study to 0.65 for the PETAL study. The radiomics model yielded an AUC of 0.71, which was significantly higher than the IPI model (p < 0.001). The AUC of the radiomics model ranged between 0.59 for the HOVON-130 study to 0.75 for the PETAL study. For all external datasets, the AUC of the radiomics model was higher than the AUC of the IPI model. Comparable results were found using 2-year TTP as outcome. The IPI model yielded an AUC of 0.62 and the radiomics model yielded an AUC of 0.71 when using all 1195 patients (p < 0.001). Again, the AUCs of the radiomics models were consistently higher than the AUCs of the IPI model for all individual studies. High-risk patients according to the IPI model had a 2-year PFS of 60.3% (95% confidence interval (CI): 54.4-67.0). High risk patients by the radiomics model had a 2-year PFS of 50.9% (95% CI: 44.8-57.7). The PPV increased from 35.5% for the IPI model to 49.1% for the radiomics model. For 2-year TTP as outcome, high-risk IPI patients had an overall survival rate of 66.4% (95%CI: 60.3-73.0). High-risk radiomics patients had a survival rate of 55.5% (95% CI: 49.1-62.6). The PPV increased from 33.7% to 44.6% for the radiomics model compared to the IPI model. Conclusion The radiomics model that was developed in the HOVON-84 dataset remained predictive of outcome in 6 independent first-line DLBCL studies, and had higher model performance than the currently used IPI risk score in all studies. Differences between IPI and radiomics model performance between individual studies are most likely caused by differences in patient characteristics between studies. Our radiomics model is able to select high-risk patients more accurately than the IPI model, with higher model performance and PPV. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal