Standardized Uptake Volume Research Articles

Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.

Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults. Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education. Amyloid [unstandardized partial regression coefficient estimate (β) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [β = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time. Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.

Associations between regional blood-brain barrier permeability, aging, and Alzheimer's disease biomarkers in cognitively normal older adults.

Increased blood-brain barrier permeability (BBBp) has been hypothesized as a feature of aging that may lead to the development of Alzheimer's disease (AD). We sought to identify the brain regions most vulnerable to greater BBBp during aging and examine their regional relationship with neuroimaging biomarkers of AD. We studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify Ktrans values, as a measure of BBBp, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)- PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBp than YA. In OA, Ktrans values were compared based on sex, Aβ positivity status, and APOE4 carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between Ktrans and AD biomarkers. OA showed greater BBBp than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in Ktrans values based on sex or Aβ positivity, but OA who were APOE4 carriers had significantly higher Ktrans values. There was no direct relationship between averaged Ktrans and global Aβ pathology, but there was a trend for an Ab status by tau interaction on Ktrans in this region. SCCA showed increased Ktrans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between Ktrans and FTP SUVR. Our findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBp in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.

The influence of Q.Clear reconstruction on the contrast recovery coefficient and semi-quantitative parameters of NEMA phantom imaging

Background: The aim of the study is to optimise the value of B parameter (β), which is used in the Q.Clear reconstruction in the imaging of neuroendocrine tumours. The study is divided into two parts: analysis of phantom data aiming at selection of the appropriate β for small changes, and then assessment of its impact on the quality of patients' images. The literature data on the optimal β value are inconclusive. Furthermore, the suggested values are not the result of the semi-quantitative assessment of Standard Uptake Volume (SUV) or the proper verification based on, for example, phantom studies using the known activity. Results: The obtained results show that β increase raises the image uniformity in the Q.Clear reconstruction algorithm. Also, referring to the scientific reports, one can see that the signal to noise ratio in the image increases. The effect of the β change on the SUV mean and Contrast Recovery Coefficient (CRC) value is greatest for the smallest objects. The decrease of this parameter is also much higher with lower values of activity (a lower counts statistic in the PET system). Conclusions: An increase of β has an adverse effect on the quality of a semi-quantitative assessment of SUV – as the parameter increases, the SUV and CRC values decrease. In the visual assessment, a satisfactory image quality is present with β = 450. Based on the analysis of SUV and CRC, an appropriate range of β values was selected as 350–450. At the selected range, a retrospective analysis of the clinical images of neuroendocrine tumours will be performed in the future and the impact of the change on the semi- -quantitative analysis of pathological changes will be verified.

Impact of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography on Therapeutic Decisions and Radiotherapy Planning in Head and Neck Squamous Carcinoma: A Retrospective Study of 46 Patients.

BACKGROUND Positron emission tomography/computed tomography (PET/CT) using fluorodeoxyglucose (FDG) is essential in oncology for precise tumor delineation. This study evaluated FDG PET/CT's impact on therapeutic decisions in head and neck cancer, comparing metabolic tumor volumes (MTV) measured by different methods with radiotherapy targets, crucial for treatment planning and patient outcomes. MATERIAL AND METHODS We retrospectively analyzed 46 patients with histologically confirmed head and neck cancer who underwent FDG PET/CT examination before radiotherapy. The mean age was 62 years (46-78 years). Then, we calculated MTV of the primary tumor or local recurrence using a local threshold of 41% of the standard uptake volume (SUV) corrected for lean body mass (SULmax) of the lesion and absolute threshold of SUV 2.5. Descriptive analysis of the recruited patients was assessed based on the clinical database (Medsol). RESULTS The study included 45 patients with squamous carcinoma and 1 with sarcoid cell carcinoma. PET/CT examination led to therapeutic decision changes in 11 cases. No significant difference was found in median values of Gross Tumor Volume (GTV) and MTV absolute (p=0.130). However, significant differences were observed in MTV local, MTV absolute, and GTV median values (p<0.001), with both MTVs showing significant correlation with GTV (p<0.01), especially MTV absolute (r=0.886). CONCLUSIONS FDG PET/CT examination prior to radiotherapy significantly influences therapeutic decisions in head and neck cancer patients. Based on our findings, the absolute threshold method (SUV: 2.5) appears to be an effective approach for calculating MTV for radiotherapy planning purposes.

Using 18F-AV-133 VMAT2 PET Imaging to Monitor Progressive Nigrostriatal Degeneration in Parkinson Disease.

There are limited validated biomarkers in Parkinson disease (PD) which substantially hinders the ability to monitor disease progression and consequently measure the efficacy of disease-modifying treatments. Imaging biomarkers, such as vesicular monoamine transporter type 2 (VMAT2) PET, enable enhanced diagnostic accuracy and detect early neurodegenerative changes associated with prodromal PD. This study sought to assess whether 18F-AV-133 VMAT2 PET is sensitive enough to monitor and quantify disease progression over a 2-year window. 18F-AV-133 PET scans were performed on participants with PD and REM sleep behavior disorder (RBD) and neurologic controls (NC). All participants were scanned twice ∼26 months apart. Regional tracer retention was calculated with a primary visual cortex reference region and expressed as the standard uptake volume ratio. Regions of interest included caudate, anterior, and posterior putamen. At the time of scanning, participants underwent clinical evaluation including UPDRSMOTOR test, Sniffin' Sticks, and Hospital Anxiety and Depression Score. Over the 26-month interval, a significant decline in PET signal was observed in all 3 regions in participants with PD (N = 26) compared with NC (N = 12), consistent with a decrease in VMAT2 level and ongoing neurodegeneration. Imaging trajectory calculations suggest that the neurodegeneration in PD occurs over ∼33 years [CI: 27.2-39.5], with ∼10.5 years [CI: 9.1-11.3] of degeneration in the posterior putamen before it becomes detectable on a VMAT2 PET scan, a further ∼6.5 years [CI: 1.6-12.7] until symptom onset, and a further ∼3 years [CI: 0.3-8.7] until clinical diagnosis. Over a 2-year period, 18F-AV-133 VMAT2 PET was able to detect progression of nigrostriatal degeneration in participants with PD, and it represents a sensitive tool to identify individuals at risk of progression to PD, which are currently lacking using clinical readouts. Trajectory models propose that there is nigrostriatal degeneration occurring for 20 years before clinical diagnosis. These data demonstrate that VMAT2 PET provides a sensitive measure to monitor neurodegenerative progression of PD which has implications for PD diagnostics and subsequently clinical trial patient stratification and monitoring. This study provides Class IV evidence that VMAT2 PET can detect patients with Parkinson disease and quantify progression over a 2-year window.

Cerebral amyloid‐β deposition in patients with diseases of the heart or carotid arteries: A systematic review and meta‐analysis

AbstractBackgroundCardiovascular disease is increasingly recognized as a contributor to cognitive impairment. Reduced cerebral blood flow alone does not explain this association. Another contributing mechanism could be increased cerebral amyloid‐β accumulation. We hypothesized that patients with diseases of the heart or carotid arteries have more cerebral amyloid‐β accumulation than patients without these diseases.MethodWe conducted a systematic review to determine whether there is an association between diseases of the heart (heart failure, myocardial infarction, heart valve diseases, arrhythmias and cardiomyopathies) or carotid arteries (stenosis or occlusion of the extracranial internal carotid arteries (ICA)) and cerebral amyloid‐β accumulation, measured with positron emission tomography. We searched Pubmed, EMBASE and Scopus for studies that matched inclusion and exclusion criteria. Where possible, we obtained standardized mean differences (SMD) of amyloid‐β standardized uptake volume ratios (SUVr) with a meta‐analysis using a random‐effects model.ResultSeven cross‐sectional studies, two on heart diseases and five on carotid artery diseases, were identified, including a total of 1262 participants (mean age 60‐76 years, 53% female). Six of the seven studies did not find a difference in cerebral amyloid‐β accumulation between patients with or without heart or carotid artery disease. One study including 11 participants found more amyloid‐β in the hemisphere ipsilateral to an ICA stenosis than in the hemisphere of healthy controls. SMD were calculated for atrial fibrillation (AF) (two studies including 746 participants) and unilateral ICA stenosis or occlusion (two studies including 24 participants). Patients with AF tended to have more cerebral amyloid‐β than reference participants (SMD in SUVr 0.14, 95% CI ‐0.06 – 0.34). There was less amyloid‐β in the hemisphere ipsilateral to the ICA stenosis or occlusion compared to the contralateral hemisphere (SMD in SUVr ‐0.13, 95% CI ‐0.70 – 0.43). Although we did not find significant effects.ConclusionCurrently available evidence does not support the notion that diseases of the heart or carotid arteries predispose for a higher burden of cerebral amyloid‐β.

Impact of 68Ga-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.

48 Background: 68Ga prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a highly sensitive diagnostic tool to detect prostate metastatic sites even at low levels of Prostate Specific Antigen (PSA). We evaluated the impact of 68Ga-PSMA PET/CT in patients treated with enzalutamide as first-line therapy for mCRPC. Methods: In an observational prospective study, 67 consecutive mCRPC patients were treated with enzalutamide 160 mg once daily in first-line for mCRPC. 68Ga-PSMA PET/CT was performed at baseline, after 3 months, during follow-up and at PSA/clinical progression. Patients were evaluated on a monthly basis for serological PSA response and safety. We measured at baseline the sum of metabolic total volume (SMTV), mean standardized uptake volume (SSUVmean), maximum standardized uptake volume (SSUVmax) and total lesion activity (STLA), which is the product of SMTV and SSUVmean, for a maximum of 20 lesions. These parameters together with baseline PSA level, Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason Score (GS) and age were analyzed by univariate and multivariate Cox regression models as potential predictors of progression-free survival (PFS) and overall survival (OS). Results: At the moment of the present analysis, 58 mCRPC patients were considered fully evaluable. The median age was 75 years (range, 47-91), ECOG PS was 0 in 47 cases (81%), 1-2 in 11 (19%), GS was &lt;8 in 22 (38%), 8-10 in 36 (62%), the median baseline PSA was 2.66 µg/L (range 0.09-197). We observed a median SMTV of 5.73 cm3, median SSUVmax of 44.85, median SSUVmean of 25.80 and median STLA of 59.66. At the median follow-up of 52 months, median PFS was 28.9 months (95% CI 16.3-43.6), median OS was not reached (95% CI 36.8-not reached). In univariate analysis, SSUVmax and STLA were significant for PFS (p=0.015 and p=0.001, respectively) and OS (p=0.026 and p=0.019, respectively), while SSUVmean was significant only for OS (p=0.028). On multivariate analysis, STLA only remained significant for PFS (p&lt;0.001) and OS (p=0.026). Conclusions: The assessment of mCRPC by 68Ga-PSMA PET/CT before starting enzalutamide was associated with longer median PFS and OS compared to prior studies using standard imaging only. STLA, expression of both volume and intensity of 68Ga-PSMA uptake, appeared the strongest parameter able to predict PFS and OS.

TDP-43 pathology effect on volume and flortaucipir uptake in Alzheimer's disease.

Alzheimer's disease (AD) patients ≥70 years show smaller medial temporal volumes despite less 18 F-flortaucipir-positron emission tomography (PET) uptake than younger counterparts. We investigated whether TAR DNA-binding protein 43 (TDP-43) was contributing to this volume-uptake mismatch. Seventy-seven participants with flortaucipir-PET and volumetric magnetic resonance imaging underwent postmortem AD and TDP-43 pathology assessments. Bivariate-response linear regression estimated the effect of age and TDP-43 pathology on volume and/or flortaucipir standardized uptake volume ratios of the hippocampus, amygdala, entorhinal, inferior temporal, and midfrontal cortices. Older participants had lower hippocampal volumes and overall flortaucipir uptake. TDP-43-immunoreactivity correlated with reduced medial temporal volumes but was unrelated to flortaucipir uptake. TDP-43 effect size was consistent across the age spectrum. However, at older ages, the cohort mean volumes moved toward those of TDP-43-positives, reflecting the increasing TDP-43 pathology frequency with age. TDP-43 pathology is a relevant contributor driving the volume-uptake mismatch in older AD participants. TDP-43 pathology affects medial temporal volume loss but not tau radiotracer uptake. Greater TDP-43 pathology effect is seen in old age due to its increasing frequency. TDP-43 pathology is a relevant driver of the volume-uptake mismatch in old AD patients.

68Ga-DOTATATE PET/BT görüntülemede somatostatin analogları ile tedavi normal hedef organların ve malign lezyonların alımında farklılık gösterir mi?

Abstract&#x0D; Objective: &#x0D; Somatostatin analogs (SSA) are used in treating low-grade neuroendocrine tumors, mainly because of their antiproliferative effect. 68Ga tetraazacyclododecantetraacetic acid-DPhe1-Tyr3-octreotate (DOTATATE) PET/CT as somatostatin receptor imaging has been widely used in recent years. However, there are conflicting publications in the literature, although there are guidelines for discontinuing the use of SSA before imaging. This study aims to investigate the effect of SSAs on Somatostatin receptor imaging.&#x0D; Material and Method: We retrospectively analyzed 253 patients who underwent 68Ga-DOTATATE PET/CT imaging between 2018 and 2022. Among these patients, those with low grades (Grade 1 and Grade 2) using SSA were included in the study. SUVmax (maximum standard uptake volume) of normal target organs, primary tumors, and metastases with the highest SUVmax in each organ were compared before and after SSA treatment. &#x0D; Results: 28 patients (16 females; 12 males, age [mean±SD], 54.82±14.27, range 18-78) with low-grade (Grade 1 and 2) NET and 68Ga-DOTATATE PET/CT imaging with SSA therapy were included in the study. Although SUVmax was decreased in the values measured after SSA application in the liver and spleen, it was not statistically significant (p&gt;0.05). There was no significant difference between SUVmax values in primary tumors and metastatic lesions in the liver, bone, lung, or lymph nodes before and after SSA application (P&gt; 0.05).&#x0D; Conclusion: In conclusion, these drugs do not need to be discontinued before 68Ga-DOTATATE PET/CT imaging for treatment follow-up in neuroendocrine tumor patients using somatostatin analogs. In addition, these drugs may help report interpretation by increasing the intensity of metastatic lesions in the liver and spleen.

Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12)

IntroductionDefinitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50–50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation.Methods and analysisThe ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization.Ethics and disseminationThis trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations.Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

APOE ε4 influences medial temporal atrophy and tau deposition in atypical Alzheimer's disease.

Apolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD. An atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence ofAPOEε4 on cross-sectional and longitudinal regional metrics. At baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus. APOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.

Correlation of Intraoperative 5-ALA-Induced Fluorescence Intensity and Preoperative 11C-Methionine PET Uptake in Glioma Surgery.

Simple SummaryIn malignant brain tumor surgery, precise identification of the tumor is essential. 5-Aminolevulinic acid (5-ALA) labels tumor cells with red fluorescence to facilitate tumor resection. On the other hand, the nuclear medicine imaging technique, positron emission tomography with 11C-methionine (MET-PET), can delineate tumors precisely but is not widely available. This study aimed to determine the correlation between intraoperative 5-ALA-induced fluorescence and preoperative MET-PET signals of gliomas. We quantitatively measured the fluorescence intensity from tumor samples and calculated the MET-PET uptake by the tumor. Our study showed that strong tumor fluorescence correlated with high MET-PET uptake and cellular proliferation. Our findings might be valuable to rapidly provide information on tumor biology at the time of surgery in circumstances where MET-PET is inaccessible.Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Methods: Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens’ ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Results: Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. Conclusions: In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index.

Day 30 SUVmax predicts progression in patients with lymphoma achieving PR/SD after CAR T-cell therapy

AbstractAbout 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P < .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

Regional beta‐amyloid and tau deposition: Results from the Framingham Heart Study

AbstractBackgroundThe Framingham Heart Study (FHS), a three‐generation community‐based cohort studying cardiovascular disease across the adult lifespan, has expanded to include positron emission tomography (PET) of beta‐amyloid (Aβ) and tau. Our aim is to characterize these pathologies in this unique sample and utilize the wide age range to assess the spatiotemporal ordering of emerging Aβ and tau.Method211 clinically‐normal adults aged 33‐74 from FHS underwent Pittsburgh Compound B (PIB) and Flortaucipir (FTP) PET. PIB and FTP were regionally quantified in Desikan regions using distribution volume ratio (DVR) for PIB and standardized uptake volume ratio (SUVR) for FTP. Three approaches were used to identify early accumulating regions: 1. A series of Age*APOE linear models to identify regions accumulating earlier in the lifespan in ε4 carriers. 2. Identification of early regions as those more frequently elevated as previously used in older adults, with Gaussian mixture models (GMM) conducted to evaluate bimodality and set biomarker positivity thresholds for each region. 3. Applied the same frequency approach using well‐validated PIB GMM thresholds based on older adults from the Harvard Aging Brain Study (HABS).ResultFor PIB, significant Age*APOE interactions (Fig. 1) were seen across multiple regions previously implicated as early‐accumulating based on elevation frequencies from older adult samples, as well as the pars opercularis (p=0.005) and lateral parietal cortices (p&lt;0.04). PIB was significantly bimodal across all ROIs (LRT&gt;36.1, p&lt;0.001; Fig. 1). Application of GMM‐based regional positivity frequencies derived within FHS versus from HABS thresholds led to substantial discrepancies in the spatiotemporal ordering of PIB (rs=0.30, p=0.17).Age*APOE effects were not detected for any tau regions, but inferior temporal (IT), middle temporal (MT), and amygdala (AM) increased with age (Fig. 2). Higher global Aβ was also associated with higher FTP SUVR in IT, MT, and a trend for AM, as well as inferior parietal and precuneus (Fig. 2).ConclusionAβ and tau mainly follow spatiotemporal patterns consistent with prior evidence in older adult samples. GMM‐based methods used in older adult samples to dichotomize biomarker positivity may be suboptimal in younger samples. Continuous approaches may better capture early Aβ and tau in younger populations.

P-011: 18F-FDG PET/MRI for imaging minimal residual disease evaluation in Multiple Myeloma

<h3>Background</h3> Functional imaging in Multiple Myeloma (MM) plays a crucial role in defining bone disease response. According to IMWG guidelines,18FDG PET/CT represents the only technique recognized to define imaging minimal residual disease (MRD) negativity. More recently, Whole body Diffusion Weighted Imaging (WB DWI)-MRI represents a non ionizing radiation imaging modality with a potential impact on evaluating myeloma bone disease response. Consequently, patients achieving both PET/CT and WB DWI-MRI negativity after treatment showed improved progression free survival (PFS) as compared to patients with single PET or MRI negativity. In the last years, a novel functional technique combining both 18FDG PET with WB DWI-MRI (PET/MRI) has been developed. In this study, we evaluated PET/MRI for bone disease response assessment in MM. <h3>Methods</h3> We retrospectively studied 27 patients (12 female and 15 male) affected by newly diagnosed active MM. All patients received a combined 18F-FDG PET/MRI registering T1w signal, T2w STIR (short tau inversion recovery) signal, DWI (diffusion weighted imaging) signal, mean ADC (apparent diffusion coefficient) value and SUV (standardized uptake volume) max value at diagnosis and at the end of the therapeutic program [after autologous stem cell transplantation (ASCT) or consolidation treatment]. PET and MRI negativity was assessed using Deauville score (DS) and MY-RADS Response Assessment Category (RAC). Median age of the entire cohort was 57 years (44-69). Considering high risk disease features, 7/27 cases were ISS III (25.9%), 2/27 were R-ISS III (7.4%) while 7/26 (26.9%) patients harbored high risk FISH abnormalities [including t(4;14), t(14;16) and del17p]. Bone lytic lesions were detected in almost all patients (24/27, 88.9%), followed by anemia (17/27, 63%), hypercalcemia (3/27, 11.1%) and renal injury (2/27, 7.4%). All patients received bortezomib-thalidomide-dexamethasone induction regimen followed by ASCT. <h3>Results</h3> At the end of the therapeutic program, the overall response rate was 92.6%, with 37% (10/27) achieving a complete response. Regarding baseline PET/MRI evaluation, focal lesions (FLs) were detected in 23 patients, with mean SUVmax of 4.4+/-2.78 and mean ADC of 963+/-264.6 mm2/s. End of treatment PET/MRI showed a PET negativity (DS<3) in 14/27 (51.9%) patients and an MRI negativity (MY-RADS<2) in 18/27 (66.7%) cases. With a median follow up of 33 months, patients with concomitant PET and MRI negativity showed improved PFS with respect to patients with PET or MRI positivity (not reached vs 58 months, p=0.0396). By multivariate analysis, concomitant PET and MRI negativity was associated with better PFS independently from ISS and FISH (p=0.0472). <h3>Conclusions</h3> To our knowledge, this is the first study evaluating PET/MRI for bone disease response in MM. Our data provide evidence that PET/MRI represents a promising tool for imaging MRD negativity evaluation, with patients being both PET and MRI negative showing improved PFS.

Myeloma Lytic Bone Lesions Characterization with WB-LDCT and 18f-FDG PET/MRI

Introduction: Bone disease is the most frequent complain of multiple myeloma (MM) and the major cause of comorbidity. IMWG established that more than one focal lesion on MRI and at least one bone lytic lesion detected on whole body low dose CT (WB-LDCT) or 18F-FDG PET/CT fulfill the criteria for bone damage requiring therapy. Most authors consider as bone disease only lytic bone lesions (LBL) caused by destruction of trabecular bone due to PCs proliferation that presents at CT an increased density value (Hounsifeld unit (HU)>0). However, lesions with fat density (HU <0) can also be detected on MM patients, sometimes representing the only detectable LBL. The aim of this study was to evaluate differences in densitometry, MRI characteristics and 18F-FDG metabolism in PET by use of PET/MRI of LBL identified by WB-LDCT in patients affected by newly diagnosed multiple myeloma (NDMM).Methods: Eighteen patients (12 male and 6 female) affected by active MM, based on the IMWG criteria, that at diagnosis underwent both WB-LDCT and 18F-FDG-PET/MRI were included in the study. Every lytic bone lesion with diameter of at least 5 mm identified by WB-LDCT was characterized for dimensions and internal densitometry (negative or positive HU) by two expert radiologists. The same lesions were then evaluated by one radiologist and one nuclear medicine physician after PET/MRI analysis, registering T1w signal, T2w STIR (short tau inversion recovery) signal, DWI (diffusion weighted imaging) signal, mean ADC (apparent diffusion coefficient) value and SUV (standardized uptake volume) max value. PET/MRI was performed within 1 month from WB-LDCT.Results: A hundred thirtyfive lytic >5 mm diameter bone lesions were recognized by WB-LDCT in patients under study. Thirtyfive lesions (mean dimension 11,09 SD ± 1,5 mm) had a negative densitometry (mean -57,57 HU; SD ± 33,13 HU) showing high signal in T1w images, low signal in STIR and DWI sequences, while 100 lesions (mean dimension 17,36 SD ± 2,64) presented positive densitometry (mean 44,87 HU; SD ± 23,89) showing low T1w signal and high signal in STIR and DWI sequences. The first group presented low ADC values (mean 0,360x10-3 mm2/sec; SD ± 0,154) and low SUV max values (mean 1,69; SD ± 0,56), while the second group showed higher ADC values (mean 0,868x10-3 mm2/sec; SD ± 0,207) and SUV max values (mean 5,04; SD ± 1,94) (Fig. 1 and Fig.2). Mean ADC values and mean SUV max values between the two groups were statistically different (p value < 0,01). Eight patients presented positive and negative density LBL, 7 patients presented only positive density LBL and 3 patients presented only negative density LBL. In two patients of this latter group who did not start therapy, negative density LBL, became positive in conjunction with biochemical progression disease during the 12 months follow up. In terms of SUV and ADC a significant concordance was found between PET and MRI for both positive and negative densitometry LBL, (91% and 94%, respectively) considering a cut off value of SUV>2 and ADC>0,6 x10-3mm2/sec as abnormal. Finally, we showed a strong statistical correlation between positive densitometry LBL and ADC value >0,8 x10-3 mm2/sec, typical of focal lesion (58% vs. 2,86%, p<0,0001) and between positive densitometry LBL and SUV value >2 (92% vs. 2,86%, p<0,0001).Conclusions: By measurement of internal densitometry, WB-LDCT differentiates two different patterns of lytic lesions: one characterized by fat replacement of trabecular bone (HU<0), likely expression of high osteoclastic activation, and one characterized by cell infiltration (HU>0). Both types of lesions can coexist in the same patient and were indicative of active disease, according to laboratory parameters. The observation that mean diameters of fatty LBL were significantly lower than that of proliferative LBL might suggest a particularly high cytokine/chemokine secreting PCs clone. Alternatively, fatty LBL might represent an early stage, which anticipates a massive infiltration by PCs. PET and MRI recognized only proliferative LBL, characterized by presence of pathological PCs within the lesion, whereas fat substitution of LBL led to a negative ADC and PET result. Then, if only PET/MRI had been evaluated, fatty LBL would have not been misleadingly considered as a proof of symptomatic disease. Especially in this subset of patients, WB-LDCT adds specific information, contributing to a proper definition of bone involvement in MM patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience.

Simple SummaryThe advent of immune-checkpoint inhibitors (ICIs) has significantly changed the management of patients with non-small cell lung cancer (NSCLC). Although the assessment of PD-L1 expression remains the gold standard for the selection of cases for immunotherapy, previous experiments have investigated whether metabolic parameters from positron emission tomography (PET) scans could have a similar predictive role. In our retrospective study, we assessed if baseline fluorodeoxyglucose PET (FDG PET) can represent a further tool for selecting patients who are eligible for ICI therapy. Among the parameters tested, a surrogate of the entire tumor burden (metabolic tumor volume, MTV) demonstrated better performance in selecting patients with adequate disease control, as well as those with better overall and progression-free survival. These promising findings from a real-world experiment stress once again the pivotal role of PET scanning in the management of patients with NSCLC, requiring further validation on larger and prospective cohorts before its implementation in the stratification of patients for immunotherapy.Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

Is SUVmax a useful marker for progression-free survival in patients with metastatic GEP-NET receiving 177Lu-DOTATATE therapy?

The prognostic potential of pretreatment maximum standardized uptake volume (SUVmax) on gallium-68-DOTATATE was evaluated with positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) in 37 patients with G1/G2 gastroenteropancreatic neuroendocrine tumors (NET) who received peptide receptor radionuclide therapy (PRRT) with lutetium-177-[DOTAo,Tyr3] octreotate (177Lu-DOTATATE) after the failure of somatostatin analogues. The mean and total SUVmax were used in 68Ga-DOTATATE PET/CT before 177Lu-DOTATATE treatment to assess the progression-free survival (PFS). The responses of the patients were evaluated as partial response in 8 (32%) patients, stable disease in 12 (48%), and progressive disease in 5 (20%). The median PFS was 18 months; longer than this threshold in 14 patients (26.0 months) and shorter in 11 (8.4 months). The mean SUVmax of metastases in the liver (34.15±17.89 vs. 14.69±9.17, P=0.004) and mean SUVmax of all body metastatic lesions (33.05±14.32 vs. 15.26±4.84, P=0.001) were higher in patientswith longer PFS. The tumor grade, the origin of the tumor, Ki67 status, and previous somatostatin treatment history were not significantly different between the two PFS groups. The pre-treatment SUVmax values of 68Ga-DOTATATE PET/CT in lesions are a potential prognostic factor for PFS in well-differentiated gastroenteropancreatic neuroendocrine tumors undergoing 177Lu-DOTATATE treatment, and could be a useful parameter for the treatment selection.

The ratio between the whole-body and primary tumor burden, measured on 18F-FDG PET/CT studies, as a prognostic indicator in advanced non-small cell lung cancer.

ObjectiveTo determine whether the whole-body tumor burden, as quantified by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT), is a prognostic indicator in advanced (stage III or IV) non-small cell lung cancer (NSCLC).Materials and MethodsThis was a prospective study in which we evaluated 18F-FDG PET/CT staging parameters to quantify tumor burdens in patients with stage III or IV NSCLC. The following parameters were evaluated for the whole body (including the primary tumor) and for the primary tumor alone, respectively: maximum standardized uptake volume (wbSUVmax and tuSUVmax); metabolic tumor volume (wbMTV and tuMTV); and total lesion glycolysis (wbTLG and tuTLG). To determine whether the 18F-FDG PET/CT parameters were associated with overall survival (OS) and progression-free survival (PFS), we evaluated the wbSUVmax/tuSUVmax, wbMTV/tuMTV, and wbTLG/tuTLG ratios.Results18F-FDG PET/CT was performed for staging in 52 patients who were followed for a median of 11.0 months (mean, 11.7 months). The estimated median PFS and OS were 9.6 months and 11.6 months, respectively. In the univariate analysis, OS was found to correlate significantly with wbTLG (hazard ratio [HR] = 1.001; 95% confidence interval [95 CI]: 1.000-1.001; p = 0.0361) and with the wbTLG/tuTLG ratio (HR = 1.705; 95% CI: 1.232-2.362; p = 0.0013). In the multivariate analysis, only the wbTLG/tuTLG ratio was independently associated with OS (HR = 1.660; 95% CI: 1.193-2.310; p = 0.0027).ConclusionThe wbTLG/tuTLG ratio is an independent prognostic indicator of OS in advanced-stage NSCLC.

Early Changes of the Standardized Uptake Values (SUVmax) Predict the Efficacy of Everolimus-Exemestane in Patients with Hormone Receptor-Positive Metastatic Breast Cancer.

Simple SummaryThe combination of everolimus and exemestane was FDA approved after BOLERO-2 clinical trial results for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (HR+ mBC), progressing on a prior therapy with a non-steroideal aromatase inhibitor. However, there are no predictive biomarkers for tumor sensitivity or resistance to everolimus-based treatment. The aim of our retrospective study was to investigate the potential role of FDG-PET SUV (ΔSUV%) as a predictive biomarker for a long-term clinical benefit. We found in a homogenous population of 31 patients two precocious ∆SUV% thresholds capable of identifying HR+ HER2-mBC patients achieving long-term benefit or long-term survival (36 month-OS) during everolimus-exemestane therapy. Based on these results, ∆SUV, as PET-based biomarker, provides additional information on which patients are most likely to benefit from everolimus with exemestane-based therapy over a long-term period. FDG-PET is a useful and minimally invasive tool that could be used for making a decision on personal treatment enhancing benefit while reducing collateral effects.Background: The mTORC1 inhibitor everolimus has been approved in combination with the aromatase inhibitor exemestane for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (HR+ mBC) progressing on prior therapy with a non-steroidal aromatase inhibitor. To date, no predictive biomarkers of tumor sensitivity/resistance for everolimus-based treatments have been identified. We hypothesized that precocious changes in the Standardized Uptake Volume (∆SUV%), as assessed by 18F-Fluorodeoxyglucosepositron-emission tomography (18F-FDG PET/CT), may be a marker of everolimus efficacy. Methods: This was a retrospective study including 31 HR+ HER2- patients treated with everolimus and exemestane in two Italian centers between 2013 and 2018. The objective of the study was to investigate ∆SUV% as a predictive marker of everolimus antitumor efficacy. 18F-FDG PET/CT scans were performed at baseline and after three months of treatment. Patients were defined as long responders (LRs) if disease progression occurred at least 10 months after treatment initiation and long survivors (LSs) if death occurred later than 36 months after starting therapy. ROC analysis was used to determine the optimal cut-off values of ∆SUV% to distinguish LRs from non-LRs and LSs from non-LSs. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method. Results: The SUVmax values decreased significantly from baseline to 3 months after therapy (p = 0.003). Dynamic changes of SUVmax (Delta SUV) had a higher accuracy in discriminating long-responders from non-long-responders (AUC = 0.67, Delta SUV cut-off = 28.8%) respects to its ability to identify long survivors from no-long survivors (AUC = 0.60, Delta SUV cut-off = 53.8%). Patients were divided into groups according to the Delta SUV cut-offs and survival outcomes were evaluated: patients with a decrease of ∆SUV% ≥ 28.8% had significantly better PFS (10 months-PFS: 63.2%, 95% CI: 37.9–80.4% and 16.7%, 95% CI: 2.7–41.3% respectively, p = 0.005). As regard as OS, patients with ∆SUV% ≥ 53.8% had longer OS when compared to patients with ∆SUV% < 53.8% (36 month-OS: 82.5% vs. 45.9% vs. p = 0.048). Conclusion: We found two precocious ∆SUV% thresholds capable of identifying HR+ HER2-mBC patients, which would achieve long-term benefit or long-term survival during everolimus-exemestane therapy. These results warrant further validation in prospective studies and should be integrated with molecular biomarkers related to tumor metabolism and mTORC1 signaling.