PET Interpretation Research Articles

The Utility of Prostate-Specific Membrane Antigen-11 PET in Detection and Management of Central Nervous System Neoplasms.

We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.2) who underwent PSMA PET imaging between March and September 2023. PET interpretation showed increased Ga-PSMA-11 accumulation in all patients with a mean SUV max of 3.11 ± 1.8. This series underscores PSMA PET's potential for CNS neoplasm detection.

An assessment of PET and CMR radiomic features for the detection of cardiac sarcoidosis.

Visual interpretation of PET and CMR may fail to identify cardiac sarcoidosis (CS) with high specificity. This study aimed to evaluate the role of [18F]FDG PET and late gadolinium enhancement (LGE)-CMR radiomic features in differentiating CS from another cause of myocardial inflammation, in this case patients with cardiac-related clinical symptoms following COVID-19. [18F]FDG PET and LGE-CMR were treated separately in this work. There were 35 post-COVID-19 (PC) and 40 CS datasets. Regions of interest were delineated manually around the entire left ventricle for the PET and LGE-CMR datasets. Radiomic features were then extracted. The ability of individual features to correctly identify image data as CS or PC was tested to predict the clinical classification of CS vs. PC using Mann-Whitney U-tests and logistic regression. Features were retained if the P-value was <0.00053, the AUC was >0.5, and the accuracy was >0.7. After applying the correlation test, uncorrelated features were used as a signature (joint features) to train machine learning classifiers. For LGE-CMR analysis, to further improve the results, different classifiers were used for individual features besides logistic regression, and the results of individual features of each classifier were screened to create a signature that included all features that followed the previously mentioned criteria and used it them as input for machine learning classifiers. The Mann-Whitney U-tests and logistic regression were trained on individual features to build a collection of features. For [18F]FDG PET analysis, the maximum target-to-background ratio (TBRmax ) showed a high area under the curve (AUC) and accuracy with small P-values (<0.00053), but the signature performed better (AUC 0.98 and accuracy 0.91). For LGE-CMR analysis, the Gray Level Dependence Matrix (gldm)-Dependence Non-Uniformity showed good results with small error bars (accuracy 0.75 and AUC 0.87). However, by applying a Support Vector Machine classifier to individual LGE-CMR features and creating a signature, a Random Forest classifier displayed better AUC and accuracy (0.91 and 0.84, respectively). Using radiomic features may prove useful in identifying individuals with CS. Some features showed promising results in differentiating between PC and CS. By automating the analysis, the patient management process can be accelerated and improved.

Measure what is measurable: PET RANO 1.0 criteria for interpretation of amino acid PET of diffuse gliomas.

Measure what is measurable: PET RANO 1.0 criteria for interpretation of amino acid PET of diffuse gliomas.

An International Survey Investigating the Incidence and Management of Brown Fat Uptake on 18F-FDG PET/CT at Children's Hospitals and Interventions for Mitigation.

Brown fat can present challenges in patients with cancer who undergo 18F-FDG PET scans. Uptake of 18F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices. We sought to characterize practice patterns for strategies to mitigate brown fat uptake of 18F-FDG during PET scanning. Methods: A survey was developed and distributed via e-mail LISTSERV to members of the Children's Oncology Group diagnostic imaging committee, the Society for Nuclear Medicine and Molecular Imaging pediatric imaging council, and the Society of Chiefs of Radiology at Children's Hospitals between April 2022 and February 2023. Responses were stored anonymously in REDCap, aggregated, and summarized using descriptive statistics. Results: Fifty-five complete responses were submitted: 51 (93%) faculty and fellow-level physicians, 2 (4%) technologists, and 2 (4%) respondents not reporting their rank. There were 43 unique institutions represented, including 5 (12%) outside the United States. Thirty-eight of 41 (93%) institutions that responded on environmental interventions reported using warm blankets in the infusion and scanning rooms. Less than a third (n = 13, 30%) of institutions reported use of a pharmacologic intervention, with propranolol (n = 5, 38%) being most common, followed by fentanyl (n = 4, 31%), diazepam (n = 2, 15%), and diazepam plus propranolol (n = 2, 15%). Selection criteria for pharmacologic intervention varied, with the most common criterion being brown fat uptake on a prior scan (n = 6, 45%). Conclusion: Clinical practices to mitigate brown fat uptake on pediatric 18F-FDG PET vary widely. Simple environmental interventions including warm blankets or increasing the temperature of the injection and scanning rooms were not universally reported. Less than a third of institutions use pharmacologic agents for brown fat mitigation.

Comparison of Expert Reads vs. Local Clinical Reads of Amyloid PET Scans in IDEAS

AbstractBackgroundAmyloid‐directed therapies will increase the clinical use of amyloid PET. IDEAS captured &gt;17,000 clinical scan interpretations from local radiologists and nuclear medicine physicians. This study aimed to establish accuracy of these interpretations by comparison to expert readers across identical scans.MethodRandomly selected amyloid PET/CT scans performed using one of three FDA‐approved agents [18F‐Florbetaben (FBB), 18F‐Florbetapir (FBP), 18F‐Flutemetamol (FMM)] and previously interpreted by local readers from the Imaging Dementia ‐ Evidence for Amyloid Scanning (IDEAS) study were assigned to vendor‐selected panels of 3 expert readers for interpretation; 500 scans per agent and 1 panel per agent. Scans were stratified to match frequencies observed in the overall study by 1) participant age; 2) MCI vs dementia; 3) positive/negative interpretation; and 4) type of PET facility. Respective vendors performed quality control on attenuation‐corrected PET/CT images.Visual interpretations (positive or negative for Aβ cortical deposition) were performed according to agent‐specific validated interpretation criteria. Expert panel readers were blinded to clinical and demographic data. Cohen’s kappa statistic with two‐sided 95% confidence interval estimates examined agreement between local reader and majority expert panel visual interpretation.ResultExpert panel readers’ visual interpretations totaled 4489. Median age for scanned participants was 75 (range 65‐96), 51.4% were female and 60.5% had MCI. Local readers interpreted 60.9% of scans positive and 39.1% negative (Table 1).Across all radiotracers, agreement between majority expert read and local readers was excellent (k coefficient 0.76; 95% CI 0.73 – 0.80, p&lt;.0001) with 86.6% (791/913) agreement for positive scans and 90.9% (532/585) agreement for negative scans (Figure 1). Agreement by individual radiopharmaceuticals was good to excellent: k coefficient 0.78 (95% CI 0.72 – 0.83, p&lt;.001) for FBB, k coefficient 0.72 (95% CI 0.66 – 0.78, p&lt;.001) for FBP, and k coefficient 0.78 (95% CI 0.73 – 0.84) for FMM (Figure 1). Agreement levels between local readers and individual experts varied from good to excellent (Figure 2).ConclusionWe found good to excellent agreement between local readers and majority assessment of three‐member expert panels for all combined scans and scans by individual agents. Visual interpretation of Aβ PET can be performed in a clinical setting with high reliability.

Impact of florbetaben acquisition timing on continuous and dichotomous measures of amyloid burden: implications for real‐world amyloid PET interpretation

AbstractBackgroundThe magnitude of Standardized Uptake Value Ratios (SUVRs) and Centiloid (CL) values increase at later acquisition windows for Florbetaben (FBB). As amyloid PET is anticipated to be utilized for treatment decisions with anti‐amyloid therapeutics (van Dyck, 2022), it is important to understand acquisition factors that influence PET quantification.MethodWe analyzed 120 FBB scans from the Stanford Alzheimer’s Disease Research Center with 5‐minute frame data spanning 70‐110 minutes post‐injection (Table 1). Frame data were motion corrected, summed into 70‐90 and 90‐110‐minute files, and processed through an MRI‐Free pipeline. A global cortical target region and whole cerebellum reference region from the GAAIN atlas were used to create SUVRs and CLs (Klunk, 2014). SUVRs and CLs computed across the two acquisition windows were compared using linear regression to understand the effects of timing acquisition on magnitude. Gaussian Mixture Models (GMM) were used to convert SUVRs to a probability scale separately for 70‐90 and 90‐110 datasets. 10,000 bootstrapped mixed timing datasets were created by randomly selecting either 70‐90 or 90‐110 SUVRs for a given participant, which was then used to understand the impact of GMM‐based classification into A‐ and A+ groups when acquisition time varies within dataset.ResultCLs were systematically lower during the earlier acquisition window (2.01 CL for the CL&lt;10 group, ΔCL range = ‐8.83,9.16; 2.89 CL for the 10‐25 group, ΔCL range = ‐2.18,9.33; 3.62 CL for the 25‐50 group, ΔCL range = ‐0.04,11.34; and 10.94 for the &gt;50 group, ΔCL range = 1.81,26.98) (Fig. 1). GMM classification into A‐ and A+ groups was consistent across the two acquisition windows and in the mixed timing datasets (Table 2).ConclusionGMM is a robust quantitative method that can be used to characterize amyloid PET scans into A‐ and A+ groups when acquisition time varies. However, given the inconsistent impact of acquisition time on CL magnitude, comparison of CL values before and after anti‐amyloid treatments will require adjustment for scan acquisition time. Future work is needed to establish methods that can measure amyloid PET change when acquisition times vary within an individual patient. This is especially important for evaluating the efficacy of currently approved anti‐amyloid therapeutic approaches.

Impact of florbetaben acquisition timing on continuous and dichotomous measures of amyloid burden: implications for real‐world amyloid PET interpretation

AbstractBackgroundThe magnitude of Standardized Uptake Value Ratios (SUVRs) and Centiloid (CL) values increase at later acquisition windows for Florbetaben (FBB). As amyloid PET is anticipated to be utilized for treatment decisions with anti‐amyloid therapeutics (van Dyck, 2022), it is important to understand acquisition factors that influence PET quantification.MethodWe analyzed 120 FBB scans from the Stanford Alzheimer’s Disease Research Center with 5‐minute frame data spanning 70‐110 minutes post‐injection (Table 1). Frame data were motion corrected, summed into 70‐90 and 90‐110‐minute files, and processed through an MRI‐Free pipeline. A global cortical target region and whole cerebellum reference region from the GAAIN atlas were used to create SUVRs and CLs (Klunk, 2014). SUVRs and CLs computed across the two acquisition windows were compared using linear regression to understand the effects of timing acquisition on magnitude. Gaussian Mixture Models (GMM) were used to convert SUVRs to a probability scale separately for 70‐90 and 90‐110 datasets. 10,000 bootstrapped mixed timing datasets were created by randomly selecting either 70‐90 or 90‐110 SUVRs for a given participant, which was then used to understand the impact of GMM‐based classification into A‐ and A+ groups when acquisition time varies within dataset.ResultCLs were systematically lower during the earlier acquisition window (2.01 CL for the CL&lt;10 group, ΔCL range = ‐8.83,9.16; 2.89 CL for the 10‐25 group, ΔCL range = ‐2.18,9.33; 3.62 CL for the 25‐50 group, ΔCL range = ‐0.04,11.34; and 10.94 for the &gt;50 group, ΔCL range = 1.81,26.98) (Fig. 1). GMM classification into A‐ and A+ groups was consistent across the two acquisition windows and in the mixed timing datasets (Table 2).ConclusionGMM is a robust quantitative method that can be used to characterize amyloid PET scans into A‐ and A+ groups when acquisition time varies. However, given the inconsistent impact of acquisition time on CL magnitude, comparison of CL values before and after anti‐amyloid treatments will require adjustment for scan acquisition time. Future work is needed to establish methods that can measure amyloid PET change when acquisition times vary within an individual patient. This is especially important for evaluating the efficacy of currently approved anti‐amyloid therapeutic approaches.

Validation of the ΔSUVmax for Interim PET Interpretation in Diffuse Large B-Cell Lymphoma on the Basis of the GAINED Clinical Trial.

The GAINED phase 3 trial (ClinicalTrials.gov identifier: NCT01659099) evaluated a PET-driven consolidative strategy in patients with diffuse large B-cell lymphoma. In this post hoc analysis, we aimed to compare the prognostic value of the per-protocol PET interpretation criteria (Menton 2011 consensus) with the change in the SUVmax (ΔSUVmax) alone. Methods: Real-time central review of 18F-FDG PET/CT was performed in 581 patients after 2 cycles (PET2) and 4 cycles (PET4) of immunochemotherapy using the Menton 2011 criteria, combining the ΔSUVmax (cutoffs of 66% and 70% at PET2 and PET4, respectively) and the Deauville scale. In "special cases," when the baseline SUVmax was less than 10.0 or the interim residual tumor SUVmax was greater than 5.0, the Menton 2011 experts' consensus agreed that the ΔSUVmax may not be reliable and that the Deauville score is preferable. Prognostic values of Menton 2011 and ΔSUVmax were evaluated by Kaplan-Meier analyses in terms of progression-free survival (PFS). Results: Seventeen percent of patients at PET2 (100/581) and 8% at PET4 (49/581) had PET-negative results by ΔSUVmax but were considered to have PET-positive results according to Menton 2011 with residual SUVmax of greater than 5.0. For the population with PET2-positive results, 2-y PFS was 70% (range, 58%-80%) with ΔSUVmax alone, whereas the outcome tended to be better for those who were considered to have PET-positive results by Menton 2011, 81% (range, 72%-87%). Conversely, all 10 patients with baseline SUVmax of less than 10.0 had PET2-positive results by ΔSUVmax but were considered to have PET2-negative results by Menton 2011. These patients had the same 2-y PFS as patients with PET2-negative/PET4-negative results, indicating that the ΔSUVmax yielded false-positive results in this situation. Conclusion: We recommend the use of the ΔSUVmax alone rather than the Menton 2011 criteria for assessing the interim metabolic response in patients with diffuse large B-cell lymphoma, except when the baseline SUVmax is less than 10.0.

Calculation of standardized uptake values (SUVs) and time activity curves (TACs) of mice in FDG-PET

Abstract Positron Emission Tomography (PET) with 18Ffluorodeoxyglucose (FDG) is an important imaging practice in cancer diagnosis, staging, treatment planning, and response assessment. Accurate interpretation of PET results requires an understanding of FDG uptake in organs. The time activity curve (TAC) and standardized uptake value (SUV) are the two common tools to measure tracer uptake in regions of interest. The TAC provides information on glucose consumption dynamics, while the SUV involves measuring the amount of tracer taken up by a specific region or volume of interest, and then adjusting the measurement by the amount of tracer injected and the subject’s characteristics. In the current study, we measured the TACs and SUVs of the heart, brain, kidney, and muscle in ten mice injected with FDG over a period of 120 minutes. According to the TACs obtained in this study, the brain has a slower uptake than the other organs with a tendency to keep the FDG for a longer period of time. Also, the SUV of the brain showed a rising trend until the middle of the experiment with a sharp falloff afterwards. The pattern of the curves of the other three organs was almost the same. The findings of this study were in agreement with a similar study on humans and are explained by the metabolic activity and physiology of the organs studied.

Complete resolution of focal-on-diffuse myocardial activity pattern on FDG PET-CT by prolonging the dietary preparation protocol in cardiac sarcoidosis.

Patient preparation is crucial for reliable interpretation of cardiac inflammation FDG PET. We share our experience of improved reporting confidence and propose a simple approach of prolonging preparation (from 24 to 48 hours) with the high-fat, no-carbohydrate, and protein-permitted diet followed by fasting in cardiac sarcoidosis in cases with diffuse or focal-on-diffuse myocardial FDG uptake.

Development of software for measuring brain amyloid accumulation using 18 F-florbetapir PET and calculating global Centiloid scale and regional Z-score values.

Quantitative measures have been proposed to aid the visual interpretation of amyloid PET. Our objective was to develop and validate quantitative software that enables calculation of the Centiloid (CL) scale and Z-score for amyloid PET with 18 F-florbetapir. This software was developed as a toolbox in statistical parametric mapping 12 running on MATLAB Runtime. For each participant's amyloid PET, this software calculates the CL scale using the standard MRI-guided pipeline proposed by the Global Alzheimer's Association Interactive Network (GAAIN) and generates a Z-score map for comparison with a new amyloid-negative database constructed from 20 healthy controls. In 23 cognitively impaired patients with suspected Alzheimer's disease, Z-score values for a target cortical area from the new database were compared with those from the GAAIN database constructed from 13 healthy controls. The CL values obtained using low-dose CT of PET/CT equipment were then compared with those obtained using MRI. The CL calculation was validated with the 18 F-florbetapir dataset in the GAAIN repository. Z-score values obtained from the new database were significantly higher (mean±standard deviation, 1.05±0.77; p<.0001) than those obtained from the GAAIN database. The use of low-dose CT provided CL scales that were highly correlated with those obtained with MRI (R2 =.992) but showed a slight yet significant underestimation (-2.1±4.2; p=.013). Our quantification software provides the CL scale and Z-score for measuring overall and local amyloid accumulation with the use of MRI or low-dose CT.

Phase III study of local or systemic therapy intensification directed by PET in prostate cancer patients with post-prostatectomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191.

TPS5118 Background: Salvage radiation therapy (sRT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). PET imaging with recently FDA-approved agents in this setting (18F-Fluciclovine, 18F-DCFPyL and 68Ga-PSMA-11), have shown improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given the greater sensitivity and specificity of PET, its findings are being increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for different treatment intensification approaches. In metastatic prostate cancer, metastasis-directed RT (MDT) has been used to avoid or delay systemic therapy in men with oligometastatic disease. Apalutamide (Apa) is an androgen receptor signaling inhibitor that has been shown to improve outcomes when added to ADT in mCSPC. This study will evaluate whether patients with PET-detected lesions outside the pelvis will benefit from addition of MDT to treatment intensification with STAD/Apa, and whether patients with no PET-detected lesions outside the pelvis will benefit from addition of Apa to standard sRT/STAD. Methods: PC pts with post-RP BCR (PSA &gt; 0.5ng/mL; &gt; 0.2ng/mL if first detectable within 12 mos of RP) and no extrapelvic metastases on CIM who are candidates for SOC ST (sRT to prostate bed and pelvic nodes with STAD) are eligible. Pts will undergo SOC baseline PET using a FDA-approved tracer. Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- MDT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death, whichever occurs first. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of MDT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish a 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified logrank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish a 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, PET progression and quality of life. Clinical trial registry number: NCT04423211. Clinical trial information: NCT04423211 .

Comparing Tau PET Visual Interpretation with Tau PET Quantification, Cerebrospinal Fluid Biomarkers, and Longitudinal Clinical Assessment.

18F-flortaucipir PET received FDA approval to visualize aggregated neurofibrillary tangles (NFTs) in brains of adult patients with cognitive impairment being evaluated for Alzheimer's disease (AD). However, manufacturer's guidelines for visual interpretation of 18F-flortaucipir PET differ from how 18F-flortaucipir PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to 18F-flortaucipir PET SUVR, cerebrospinal fluid (CSF) biomarkers, or longitudinal clinical assessment is not well understood. We compare various diagnostic methods in participants enrolled in longitudinal observational studies of aging and memory (n = 189, 23 were cognitively impaired). Participants had tau PET, Aβ PET, MRI, and clinical and cognitive evaluation within 18 months (n = 189); the majority (n = 144) also underwent lumbar puncture. Two radiologists followed manufacturer's guidelines for 18F-flortaucipir PET visual interpretation. Visual interpretation had high agreement with SUVR (98.4%)and moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated 18F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases. Visual interpretation was highly consistent with SUVR (discordant participants had hemorrhagic infarcts or occipital-predominant AD NFT deposition) and moderately consistent with CSF p-tau181 (discordant participants had AD pathophysiology not detectable on tau PET). However, close association between AD NFT deposition and clinical onset in group-level studies does not necessarily hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.

Phase III study of local or systemic therapy intensification directed by PET in prostate cancer patients with post-prostatectomy biochemical recurrence (INDICATE): ECOG-ACRIN EA8191.

TPS402 Background: Salvage radiation therapy (sRT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). PET imaging with recently FDA-approved agents in this setting (18F-Fluciclovine, 18F-DCFPyL and 68Ga-PSMA-11), have shown improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given the greater sensitivity and specificity of PET, its findings are being increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for different treatment intensification approaches. In metastatic prostate cancer, metastasis-directed RT (MDT) has been used to avoid or delay systemic therapy in men with oligometastatic disease. Apalutamide (Apa) is an androgen receptor signaling inhibitor that has been shown to improve outcomes when added to ADT in mCSPC. This study will evaluate whether patients with PET-detected lesions outside the pelvis will benefit from addition of MDT to treatment intensification with STAD/Apa, and whether patients with no PET-detected lesions outside the pelvis will benefit from addition of Apa to standard sRT/STAD. Methods: PC pts with post-RP BCR (PSA&gt;0.5ng/mL; &gt;0.2ng/mL if first detectable within 12 mos of RP) and no extrapelvic metastases on CIM who are candidates for SOC ST (sRT to prostate bed and pelvic nodes with STAD) are eligible. Pts will undergo SOC baseline PET using a FDA-approved tracer. Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- MDT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death, whichever occurs first. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of MDT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish a 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified logrank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish a 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, PET progression and quality of life. Clinical trial information: NCT04423211 .

Is local review of positron emission tomography scans sufficient in diffuse large B-cell lymphoma clinical trials? A CALGB 50303 analysis.

Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS). In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. Agreement between local and central review was moderate (kappa=0.53) for VSS and high (kappa=0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p=0.03) and OS (p=0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials.

Tau positron emission tomography in patients with cognitive impairment and suspected Alzheimer's disease.

Alzheimer's disease (AD) is diagnosed by the presence of both amyloid β and tau proteins. Recent advances in molecular PET imaging have made it possible to assess the accumulation of these proteins in the living brain. PET ligands have been developed that bind to 3R/4R tau in AD, but not to 3R tau or 4R tau alone. Of the first-generation PET ligands, 18F-flortaucipir has recently been approved by the Food and Drug Administration. Several second-generation PET probes with less off-target binding have been developed and are being applied clinically. Visual interpretation of tau PET should be based on neuropathological neurofibrillary tangle staging instead of a simple positive or negative classification. Four visual read classifications have been proposed: "no uptake," "medial temporal lobe (MTL) only," "MTL AND," and "outside MTL." As an adjunct to visual interpretation, quantitative analysis has been proposed using MRI-based native space FreeSurfer parcellations. The standardized uptake value ratio of the target area is measured using the cerebellar gray matter as a reference region. In the near future, the Centiloid scale of tau PET is expected to be used as a harmonized value for standardizing each analytical method or PET ligand used, similar to amyloid PET.

Deauville score versus ratio Deauville score in the interpretation of interim 18F-FDG PET-CT and in prediction of outcome in children with FDG-avid extra-nodal lymphomas

BackgroundPediatric lymphoma is a common hematological neoplasm, representing the third most frequent childhood malignancy. 18F-fluoro-2-deoxyglucose–positron emission tomography has been found to be useful in lymphoma staging, prediction of prognosis and risk stratification of lymphoma patients. Although the interpretation of interim PET (after two cycles of chemotherapy) using the qualitative visual method of 5-point Deauville score has been widely accepted, semiquantitative methods of interpretation were evaluated by many studies and showed a better prediction of prognosis. The purpose of this study was to evaluate the prognostic role of the semiquantitative ratio Deauville score (rDS), defined as the ratio between target lesion and liver maximum standardized uptake values in children with FDG-avid extra-nodal lymphomas, undergoing interim FDG-PET/CT, and to compare it with the 5-point Deauville score (5p-DS).MethodsThis prospective study included 89 children with FDG-avid extra-nodal lymphoma. Interim PET was interpreted using both visual (5p-DS) and the semiquantitative method (rDS). The visual method depends on visual comparison of FDG uptake between lesions and liver as a reference organ for activity and considered lesions with activity higher than liver to be positive, while the semiquantitative method depends on making a ratio between the most active lesion and liver SUVmax. Receiver operating characteristic approach was applied to identify the optimal cut-point of rDS with respect to response to therapy and prognosis, and the prognostic significance of rDS was compared with 5p-DS.ResultsThe ROC analysis for rDS as a predictor of progression showed an optimal cut-point of 1.25. Both 5p-DS and rDS were strong outcome predictors. Patients with negative 5p-DS and patients with rDS < 1.25 had a similar 3-year PFS (87%). Patients with a positive 5p-DS had a 3-year PFS of 67.4%, while patients with rDS > 1.25 had a 3-year PFS of 60%.ConclusionsrDS could be suggested as an accurate prognostic factor in children with lymphoma undergoing interim FDG-PET/CT. However, larger studies with more homogenous sample regarding histopathological subtypes and chemotherapy lines are needed to confirm these data.

Added value of coronary artery calcium score in the reporting of SPECT versus PET myocardial perfusion imaging

BackgroundKnowledge of coronary artery calcium score (CACS) influences the interpretation of myocardial perfusion imaging (MPI) with SPECT; however, the impact on PET interpretation remains unclear. We compared the added value of CACS to reporting MPI using SPECT vs PET. MethodsWe retrospectively included 412 patients. 206 patients who underwent Rb-82 PET were propensity-based matched to a cohort of 4018 patients who underwent cadmium–zinc–telluride SPECT MPI to obtain a comparable group of 206 SPECT patients. Next, we created four image sets: SPECT MPI-only, PET-only, SPECT + CACS, and PET + CACS. Two physicians interpreted the 824 images as normal, equivocal, or abnormal for ischemia or irreversible defects. Additionally, event rates were compared between PET and SPECT groups during 30-month follow-up. ResultsPET yielded more scans interpreted as normal than SPECT (88% vs 80%, respectively, P = 0.015). Adding CACS to SPECT increased the percentage of normal scans to 86% (P = 0.014), whereas this effect was absent for PET (90%, P = 0.77). Annualized event rates for images interpreted as normal did not differ and varied between 0.7 and 2.0% (P > 0.084). ConclusionAdding CACS correctly increased the percentage of normal scans for SPECT MPI but not for PET, possibly limiting the effect of adding CACS to reporting PET.

PET Imaging of Dementia: Update 2022.

PET imaging plays an essential role in achieving earlier and more specific diagnoses of dementia syndromes, important for clinical prognostication and optimal medical management. This has become especially vital with the recent development of pathology-specific disease-modifying therapy for Alzheimer disease, which will continue to evolve and require methods to select appropriate treatment candidates. Techniques that began as research tools such as amyloid and tau PET have now entered clinical use, making nuclear medicine physicians and radiologists essential members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice. Within this framework, multiple cases will be shown to illustrate a systematic approach of FDG PET interpretation and integration of PET imaging of specific molecular pathology including dopamine transporters, amyloid, and tau. The approach presented here incorporates contemporary understanding of both common and uncommon dementia syndromes, intended as an updated practical guide to assist with the sophisticated interpretation of nuclear medicine examinations in the context of this rapidly and continually developing area of imaging.

The Combined Interpretation of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in Metastatic Gastroenteropancreatic Neuroendocrine Tumors: A Classification System With Prognostic Impact.

Gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) are widely heterogeneous in their biological behavior, and predicting prognosis and optimal treatment strategies can be challenging. 68Ga-DOTATATE PET/CT is a sensitive imaging modality for well-differentiated NEN and indicates a favorable prognosis, whereas 18F-FDG PET/CT avidity indicates disease that is potentially more aggressive. There has been emerging interest in the combined interpretation of 68Ga-DOTATATE and 18F-FDG PET and its prognostic significance. We aimed to assess the prognostic utility of a classification system that incorporates the complex findings of 68Ga-DOTATATE and 18F-FDG PET interpreted side-by-side in patients with metastatic GEP NEN. We defined 3 68Ga-DOTATATE/18F-FDG "dual-tracer PET" groups: D1 (68Ga-DOTATATE positive/18F-FDG negative), D2 (68Ga-DOTATATE positive/18F-FDG positive), and D3 (68Ga-DOTATATE negative/18F-FDG positive). We retrospectively assessed the association between the dual-tracer PET classification and progression-free and overall survival (OS) using Kaplan-Meier analysis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Eighty-seven patients with metastatic GEP NEN and contemporaneous 68Ga-DOTATATE and 18F-FDG PET were included. The dual-tracer PET classification was an independent predictor of OS (multivariate P = 0.016) and also predicted progression-free survival (univariate P = 0.030). Other independent predictors of OS included chromogranin A and World Health Organization (WHO) grade. WHO grade was not associated with OS from the time of dual-tracer PET but was an independent predictor of OS from the date of histological diagnosis (multivariate P = 0.003). Our study demonstrates that a classification system combining the complex findings of 68Ga-DOTATATE and 18F-FDG PET is correlated with prognosis. Further research is needed to prospectively validate these findings and to explore whether dual-tracer PET scores may also be able to predict response to treatment.