Mean Standardized Uptake Value Research Articles

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Does enzalutamide related PSMA upregulation affect outcomes of lutetium-177 PSMA radioligand therapy?

Enzalutamide is an antiandrogen drug used prior to lutetium-177 prostate specific membrane antigen (Lu-PSMA) radioligand therapy and has shown promising results for upregulating the PSMA expression on prostate cancer cells. In this study, we aim to compare prostate specific antigen (PSA) level changes in prostate cancer patients who received enzalutamide to those who did not. Prostate cancer patients who underwent Lu-PSMA between 2021 and 2023 were retrospectively included. Patients were grouped based on prior enzalutamide therapy: those who received enzalutamide (EZ+) for at least 14 days and those who did not (EZ-). PSA changes and F-18 DCFPyL SUV (Standardized Uptake Values) were compared. Thirty-seven patients were included, 18 EZ+ and 19 EZ-. The median age, Gleason score, and prior chemo/hormonal therapies were similar for EZ+ and EZ-, except for radium-223. Eleven patients (61%) in EZ+ and 13 patients (68%) in EZ- showed a decrease in PSA after the first cycle (p = 0.64). Four patients (22%) in EZ+ and seven patients (37%) in EZ- had more than 50% decrease in PSA after the first cycle (p = 0.33). The average percent decline at the end of the treatment was 23.3% in EZ+ and 50.4% in EZ- (p = 0.4). There was no difference in terms of lesion with highest SUVmax, mean SUV, total tumor volume or activity on pre-therapy PSMA imaging. Enzalutamide treatment prior to Lu-PSMA does not improve patient outcomes when applied remotely. Larger studies evaluating the combination therapies and the timing of enzalutamide are needed to assess its correlation with Lu-PSMA outcomes.

Clinical value of semi-quantitative parameters in 68Ga-DOTANOC PET/CT in treatment and diagnostics of cranial meningioma in a single-center retrospective analysis

BackgroundThe value of somatostatin-analogon PET tracers in theranostics in cranial meningioma has been demonstrated in several studies however, the value of semi-quantitative parameters for therapy and patient outcome is still unclear.MethodsA retrospective study was performed comparing measured semi-quantitative 68Ga-DOTANOC PET/CT parameters (maximum standardized uptake value = SUVmax, mean standardized uptake value = SUVmean, and metabolic tumor volume = MTV) and calculated ratios (SUVmax tumor/to pituitary gland, SUVmax tumor to superior sinus sagittalis), versus WHO grades and overall outcome. Patients with histological confirmed meningioma or high probability for meningioma in previous cranial MRI were eligible.ResultsThirty-two patients from January 2018 to February 2023 were retrospectively included. WHO grade I meningioma was confirmed in 17 patients, WHO grade II in five patients, WHO grade III in two patients, while in eight patients diagnosis was solely based on MRI and 68Ga-DOTANOC PET/CT findings. In 12 cases stable disease was present, in 15 cases radiation therapy was chosen, in three cases neurosurgery was preferred while in two cases palliative care was chosen. Median SUVmax values increased with WHO grade (15.84, 17.22, and 28.4, p = 0.134, Kruskal–Wallis-test) and no statistically significant difference was present for MTV, SUVmax, and calculated ratios, although the ratio for SUVmax tumor to superior sinus sagittalis had the lowest value of p = 0.067.ConclusionIncreased SUVmax values in the tumor in 68Ga-DOTANOC PET/CT are associated with higher WHO grade, although further studies including larger patient collectives are needed to solidify this hypothesis.

Fluorine-18 fluorodeoxyglucose uptake change in liver, mediastinal blood pool, and lymphoid cell-rich organs during programmed cell death-1 immunotherapy in lymphoma.

The aim of this study was to evaluate metabolism change in reference organs (liver and mediastinum) and lymphoid cell-rich organs (spleen and bone marrow) during programmed cell death-1 immunotherapy in relapsed or refractory lymphoma patients. A total of 66 patients with baseline and serial monitoring fluorodeoxyglucose (FDG) PET/computed tomography scans were retrospectively enrolled. Mean standardized uptake value (SUV) and maximum SUV of evaluated organs were obtained by two reviewers, and their association with tumor burden and clinical response were evaluated. Immune-related adverse events detected by FDG PET/computed tomography were also recorded. The SUV values of reference organs and lymphoid cell-rich organs did not change significantly during the immunotherapy process. The intersubject variability of these values ranged from 13.0 to 28.5%. Meanwhile, metabolism of reference organs was affected by neither the tumor burden nor clinical response. SUV change of lymphoid cell-rich organs was associated with clinical response to immunotherapy. Responders showed decreased metabolism, while nonresponders showed a reverse trend (spleen SUVmaximum: -0.30 ± 0.47 vs. 0.18 ± 0.39, P = 0.001, spleen SUVmean: -0.24 ± 0.39 vs. 0.14 ± 0.31, P = 0.001; and bone marrow SUVmaximum: -0.14 ± 0.37 vs. 0.07 ± 0.46, P = 0.042, respectively). The influence of immune-related adverse events on the SUV change in evaluated organs was NS. During programmed cell death-1 immunotherapy, metabolism change of reference organs is influenced neither by tumor burden nor by clinical response, while FDG uptake change of lymphoid cell-rich organs is significantly associated with clinical response.

Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

Abstract PO3-07-10: Advanced CD8 ImmunoPET imaging predicts radiation response in primary TNBC

Abstract Background: Tumor immunology and immunosuppression has been observed to drive changes in intratumoral response to cytotoxic and immunotherapy in triple negative breast cancer (TNBC). While radiation therapy is standard of care for TNBC, there is a lack of research into the relationship between long term treatment response and CD8 immune infiltration in the context of a radiation resistant model. Positron emission tomography (PET) imaging allows for noninvasive monitoring of the tumor microenvironment that can precede changes in tumor volume, including approaches that allow for immune imaging of CD8 T-cell trafficking. Noninvasive PET imaging of radiation response has the potential to identify windows of enhanced response to secondary therapy and can guide interventional therapy. The goal of this study is to understand how radiation can prime the tumor microenvironment to be combined with other therapeutics in TNBC through changes in CD8 immune infiltration with [89Zr]-CD8 ImmunoPET imaging. Methods: Syngeneic parental 4T1 (radiation sensitive) and a developed radiation-resistant 4T1 sub-cell line were orthotopically injected into BALB/c mice (N = 5 control, N = 9-10 radiation treated for each model). After reaching a tumor volume of ~100 mm3, mice began treatment with 2 Gy fractionated radiation daily from day 0-5. On day 6, mice were injected with ~50 µCi of [89Zr]-CD8 minibody (IAB42) and imaged 24 hours post injection. The mean standardized uptake value (SUV) was quantified and normalized to heart SUV to extract out a tumor:heart SUVratio that describe the CD8 infiltration within tumors. Following imaging, tumors were either excised immediately for immunofluorescence against CD8 or monitored for longitudinal changes in tumor volume. A non-parametric T-test was used to assess for significance between groups. Results: In radiation sensitive 4T1 tumors, [89Zr]-CD8 ImmunoPET imaging indicated a 23% increase in CD8 immune infiltration, in radiation-treated tumors compared to control tumors on day 7 (p = 0.02). These immune alterations occurred prior to any changes in tumor volume (p = 0.63). Longitudinally, radiation treated tumors exhibited significant changes in tumor volume beginning on day 20 (p = 0.02), which is sustained until study endpoint on day 41 (p &amp;lt; 0.01). In radiation resistant 4T1 tumors, no significant change was observed in short term CD8 immune infiltration (p = 0.43) or in longitudinal tumor volume (p = 0.31) in response to radiation therapy, when compared to untreated tumors. Conclusions: [89Zr]-CD8 ImmunoPET imaging reveals significant increases in CD8 immune infiltration that is predictive of eventual response to radiation therapy in radiation sensitive models of TNBC. [89Zr]-CD8 PET imaging of radiation therapy response has the potential to increase the efficacy of precision medicine and prime the tumor microenvironment for secondary therapeutics, thereby improving tumor kill and reducing patient toxicity. Citation Format: Patrick Song, Shannon Lynch, Chloe DeMellier, Alessandro Mascioni, Fang Jia, Anna Sorace. Advanced CD8 ImmunoPET imaging predicts radiation response in primary TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-10.

Abstract PO2-13-03: Spatial HER2 heterogeneity on HER2-PET in HER2-low and negative disease: potential biomarker for antibody-drug conjugate effect

Abstract Background: Anti-HER2 antibody drug conjugates (ADCs) can assert an effect in part of patients with HER2-low breast cancer. In light of patient burden and financial sustainability, biomarkers to select responding patients are urgently needed, but so far, none have been identified. In the IMPACT trial (NCT01957332), patients with newly diagnosed and non-rapidly progressive metastatic breast cancer (MBC) of all subtypes (including HER2-negative, -low, and –positive disease) were included. We assessed the performance of Zirconium-89 (89Zr)-trastuzumab positron emission tomography (HER2-PET) in HER2-low and negative MBC. Methods: All patients received extensive workup, including a metastasis biopsy and HER2-PET at baseline. HER2 status was determined by immunohistochemistry (IHC) and in situ hybridization. ⁸⁹Zr-trastuzumab uptake was quantified as maximum and mean standardized uptake values (SUVmax, SUVmean) in metastases and healthy background tissue. Quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, was related to HER2 IHC status. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases. With increasing HER2 IHC status, uptake was higher (geometric mean SUVmax 7.0, 7.6, 7.3, and 17.4 with HER2 IHC 0, 1, 2, or 3+, in respectively 71, 71, 20, and 24 biopsied metastases (P  0.001 between IHC 0 and 3+). SUVmax in lesions was heterogeneous within and between patients for all HER2 IHC groups. All HER2 IHC groups, also HER2-negative and -low, had uptake exceeding that of the healthy background (geometric mean tumor-to-background ratio SUVmax &amp;gt;1 in all groups, increasing with higher HER2 IHC). Of patients with a HER2 IHC 0 biopsy, 27.8% had at least one metastasis elsewhere in the body, with uptake exceeding the overall 90th SUVmax percentile of 14.6; in HER2 low IHC1+ and 2+, this was 31.9% and 30%. Conclusions: In this largest series with HER2-PET in patients with MBC, we show that ±30% of patients with HER2-low or -negative IHC in the biopsy, in fact, have metastases with high HER2 uptake elsewhere in the body. This spatial heterogeneity provides novel insights into HER2-negative and -low disease compared to standard HER2 IHC of a single biopsy. As HER2-PET uptake is related to ADC response in HER2 positive MBC1, HER2-PET is a potential biomarker for anti-HER2 ADC effect in HER2-low and -negative MBC as well. Reference: 1. Gebhart G, et al. Ann Oncol 2016;27(4): 619-624. Supported by the Dutch Cancer Society grant 2012-5565 Citation Format: Carolien Schroder, Jasper van Geel, Bertha Eisses, Adrienne Brouwers, Sjoerd Elias, Frederike Bensch, Evelien Kuip, Agnes Jager, Andor Glaudemans, Bert van der Vegt, Willemien Menke-van der Houven van Oordt, Elisabeth de Vries. Spatial HER2 heterogeneity on HER2-PET in HER2-low and negative disease: potential biomarker for antibody-drug conjugate effect [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-03.

Correlation analysis between the quantitative parameters of iodine-131 single-photon emission computed tomography-computed tomography thyroid bed uptake and the efficacy of radioactive iodine adjuvant therapy for papillary thyroid cancer.

Single-photon emission computed tomography-computed tomography (SPECT/CT) quantification has emerged as a valuable tool for assessing disease prognosis by accurately identifying and characterizing abnormal lesions with accumulated radionuclides. Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, and radioactive iodine (RAI) therapy is a standard treatment following total thyroidectomy. This study aimed to explore the potential utility the quantitative parameters of the thyroid bed under iodine-131 (I-131) SPECT/CT in the efficacy of RAI adjuvant therapy for patients with PTC. The retrospective cohort study enrolled 107 patients with PTC who underwent RAI adjuvant therapy from June 2020 to January 2023. Three days after the RAI adjuvant therapy, all patients underwent I-131 whole-body scans and SPECT/CT imaging. The quantitative parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and percent injected dose (%ID), were measured using image analysis software based on I-131 SPECT/CT thyroid bed uptake. Successful therapy was defined as inhibitory thyroglobulin (Tg) <0.2 ng/mL with negative thyroglobulin antibody (TgAb) and negative imaging examination 6 months after RAI adjuvant therapy. The relationship between the quantitative parameters and the treatment efficacy, in addition to the potential influencing factors, were analyzed. The quantitative parameters from the successful group [SUVmax: median 6.15 g/mL, interquartile range (IQR) 2.34-13.80 g/mL; SUVmean: median 2.02 g/mL, IQR 0.89-4.93 g/mL; %ID: median 2.00%, IQR 1.00-4.00%] were significantly lower than those from the unsuccessful group (SUVmax: median 19.03 g/mL, IQR 5.31-45.10 g/mL, SUVmean 4.64 g/mL, IQR 2.07-19.05 g/mL; %ID: median 8.00%, IQR 3.00-18.00%) (SUVmax: Z=-3.755; SUVmean; Z=-3.671; %ID: Z=-4.070; all P values <0.001). SUVmax, SUVmean and %ID were positively correlated with the stimulated thyroglobulin (sTg) and inhibitory Tg at 6 months after RAI adjuvant therapy, respectively (all P values <0.001). SUVmax [odds ratio (OR) =1.045], SUVmean (OR =1.130), and %ID (OR =1.092) were predictive factors for the failure of RAI adjuvant therapy (all P values <0.001). Our study suggested that quantitative parameters (SUVmax, SUVmean, and %ID) derived from I-131 SPECT/CT imaging of the thyroid bed can serve as useful tools for predicting therapy outcomes following RAI adjuvant therapy.

Clinical value of semi-quantitative parameters in 68Ga-DOTANOC PET/CT in treatment and diagnostics of cranial meningioma in a single-center retrospective analysis

BackgroundThe value of somatostatin-analogon PET tracers in theranostics in cranial meningioma has been demonstrated in several studies; however, the value of semi-quantitative parameters for therapy and patient outcome is still unclear.MethodsA retrospective study was performed comparing measured semi-quantitative 68Ga-DOTANOC PET/CT parameters (maximum standardized uptake value = SUVmax, mean standardized uptake value = SUVmean, and metabolic tumor volume = MTV) and calculated ratios (SUVmax tumor to pituitary gland and SUVmax tumor to superior sinus sagittalis), versus the WHO grades and overall outcome. Patients with histological confirmed meningioma or high probability for meningioma in the previous cranial MRI were eligible.ResultsThirty-two patients from January 2018 to February 2023 were retrospectively included. The WHO grade I meningioma was confirmed in 17 patients, the WHO grade II in five patients, and the WHO grade III in two patients, while in eight patients, diagnosis was solely based on MRI and 68Ga-DOTANOC PET/CT findings. In 12 cases, stable disease was present, in 15 cases, radiation therapy was chosen, in three cases, neurosurgery was preferred, while in two cases, palliative care was chosen. Median SUVmax values increased with the WHO grade (15.84, 17.22, and 28.4, p = 0.134, Kruskal–Wallis test), and no statistically significant difference was present for MTV, SUVmax, and calculated ratios.ConclusionIncreased SUVmax values in the tumor in 68Ga-DOTANOC PET/CT are associated with higher WHO grade, although further studies including larger patient collectives are needed to solidify this hypothesis.

Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study.

Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

[18F]fluorodeoxyglucose positron emission tomography/computed tomography in combination with clinical data in predicting overall survival in non-small-cell lung cancer patients: A retrospective study

IntroductionPositron emission tomography/computed tomography (PET/CT) has an established role in evaluating patients with lung cancer. The aim of this work was to assess the predictive capability of [18F]Fluorodeoxyglucose ([18F]FDG) PET/CT parameters on overall survival (OS) in lung cancer patients using an artificial neural network (ANN) in parallel with conventional statistical analysis. MethodsRetrospective analysis was performed on a group of 165 lung cancer patients (98M, 67F). PET features associated with the primary tumor: maximum and mean standardized uptake value (SUVmax, SUVmean), total lesion glycolysis (TLG) metabolic tumor volume (MTV) and area under the curve-cumulative SUV histogram (AUC-CSH) and metastatic lesions (SUVmaxtotal, SUVmeantotal, TLGtotal, and MTVtotal) were evaluated. In parallel with conventional statistical analysis (Chi-Square analysis for nominal data, Student's t test for continuous data), the data was evaluated using an ANN. There were 97 input variables in 165 patients using a binary classification of either below, or greater than/equal to median survival post primary diagnosis. Additionally, phantom study was performed to assess the most optimal contouring method. ResultsMales had statistically higher SUVmax (mean: 10.7 vs 8.9; p = 0.020), MTV (mean: 66.5 cm3 vs. 21.5 cm3; p = 0.001), TLG (mean 404.7 vs. 115.0; p = 0.003), TLGtotal (mean: 946.7 vs. 433.3; p = 0.014) and MTVtotal (mean: 242.0 cm3 vs. 103.7 cm3; p = 0.027) than females. The ANN after training and validation was optimised with a final architecture of 4 scaling layer inputs (TLGtotal, SUVmaxtotal, SUVmeantotal and disease stage) and receiving operator characteristic (ROC) analysis demonstrated an AUC of 0.764 (sensitivity of 92.3%, specificity of 57.1%). ConclusionConventional statistical analysis and the ANN provided concordant findings in relation to variables that predict decreased survival. The ANN provided a weighted algorithm of the 4 key features to predict decreased survival. Implication for practiceIdentification of parameters which can predict survival in lung cancer patients might be helpful in choosing the group of patients who require closer look during the follow-up.

Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

Diagnostic Performance of 18F-FDG Positron Emission Tomography/Computed Tomography and Blood Test Parameters for Pulmonary Inflammatory Pseudotumor.

Pulmonary inflammatory pseudotumor (PIP) is an inflammatory proliferative tumor-like lesion that frequently exhibits hypermetabolism on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging (PET/CT) and is readily misdiagnosed as a malignant tumor. The purpose of this study was to identify PIP by combining PET/computed tomography metabolic and blood test characteristics with machine learning. We recruited 27 patients with PIP and 28 patients with lung cancer (LC). The PET metabolic and blood test parameters were collected, and the differences between the groups were evaluated. In addition, we combined the support vector machine (SVM) classifier with the indicators that differed between the groups to classify PIP and LC. For PET metabolic parameters, our findings showed that, as compared with the LC group, maximal standardized uptake value (P< 0.001, t = -4.780), Mean standardized uptake value SUVmean, P< 0.001, t = -4.946), and SD40% (P< 0.001, t = -4.893) were considerably reduced in the PIP group, whereas CV40% (P= 0.004, t = 3.012) was significantly greater. For blood test parameters, the total white blood cell count (P< 0.001, t= 6.457) and absolute neutrophil count (P< 0.001, t= 6.992) were substantially higher in the PIP group than in the LC group. Furthermore, the performance of SVM trained solely on PET metabolic parameters (mean area under the curve [AUC] = 0.84) was comparable to that of SVM trained solely on blood test parameters (mean AUC = 0.86). Surprisingly, utilizing the combined parameters increased SVM performance significantly (mean AUC = 0.98). PET metabolic and blood test parameters differed significantly between the PIP and LC groups, and the SVM paradigm using these significantly different features has the potential to be used to classify PIP and LC, which has important clinical implications.

Correlation of 18F-sodium fluoride uptake and radiodensity in extraosseous metastases of medullary thyroid carcinoma.

Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, itcan also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT)and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastasesof MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.

Evaluating the biodistribution for [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET/CT with an inter- and intrapatient based analysis

BackgroundLiver uptake in [68Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [177Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [68Ga]Ga-PSMA-11 was replaced by [18F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007.MethodsFifty patients who underwent PET examinations in two centers with both [18F]F-PSMA-1007 and [68Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUVmean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison.ResultsLiver SUVmean was significantly higher with [18F]F-PSMA-1007 (11.7 ± 3.9) compared to [68Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUVmean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUVmean on [18F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUVmean [68Ga]Ga-PSMA-11 = 0.33 x SUVmean [18F]F-PSMA-1007 + 1.52 (r = .78, p < .001).ConclusionComparing biodistribution of [68Ga]Ga and [18F]F tracers, liver uptake on [68Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [18F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [18F]F-PSMA-1007 as a basis for RLT selection.

The lesion detection rate of Ga-68 DOTATATE PET/MR in multiple endocrine neoplasia type 1.

The purpose of the study was to determine the usefulness of Ga-68 DOTATATE PET/MR in the identification of tumours in individuals with multiple endocrine neoplasia type 1 (MEN1). In this retrospective investigation, five individuals who had tested positive for a hereditary MEN1 variant underwent Ga-68 DOTATATE PET/MR between May 2020 and January 2023. Several types of tumours associated with MEN1 were studied. MEN1-related tumours included pituitary, parathyroid, gastroenteropancreatic, and adrenal. The rates of lesion identification between MRI, Ga-68 DOTATATE PET, and Ga-68 DOTATATE PET/MRI were examined. The maximum and mean standard uptake values (SUVmax and SUVmean) were evaluated in carefully delineated volumes of interest (VOI) for the relevant tumours. Of the 24 primary lesions, 14 were identified by Ga-68 DOTATATE PET, 18 by MRI, and 20 by Ga-68 DOTATATE PET/MRI. Two pituitary tumours were detected by all three techniques. All parathyroid tumours that were not detected by Ga-68 DOTATATE PET and MRI were found by Tc-99m MIBI SPECT/CT or/and EUS. Ga-68 DOTATATE PET/MR detected more gastroenteropancreatic lesions. All adrenal tumours not identified by Ga-68 DOTATATE PET were found by MRI or CT. The median SUVmax for lesions identified on Ga-68 DOTATATE PET/MRI was 18.4 (range, 3.8-85.2), and the median SUVmean was 12.0 (range, 2.3-49.8). The combination of Ga-68 DOTATATE PET and MRI demonstrated a higher detection rate and may be more useful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. To increase the identification of MEN1-associated neuroendocrine lesions in the parathyroid gland, approaches other than Ga-68 DOTATATE PET/MRI should be used.

472 Utility of [89Zr]Trastuzumab-PET/MRI Imaging for Quantitative Assessment of Tumor Heterogeneity In HER2+ Breast Cancer

OBJECTIVES/GOALS: This study was performed to explore the capabilities of simultaneous [89 Zr]trastuzumab-PET/MRI acquisition in a cohort of metastatic HER2+ breast cancer. The insights derived provide additional noninvasive characterization and precise intratumoral analysis tools for healthcare providers. METHODS/STUDY POPULATION: A total of 13 patients, aged between 40 and 70, diagnosed with HER2-positive breast cancer, were selected to participate in this study. Whole-body [89 Zr]trastuzumab-PET/MR imaging was performed 5 ± 1 days post-injection of the radiopharmaceutical during ongoing HER2-directed therapy. Concurrently acquired T1-weighted MRI facilitated the identification of normal organ and tumor regions of interest, which were further analyzed for mean ADC and mean standardized uptake value. Multiparametric intratumoral habitat analysis was performed. Utilizing the median metric values, tumors were evaluated for heterogeneity, specifically assessing high and low HER2 expression through an image processing framework in conjunction with ADC metrics. Long-term treatment response evaluation is ongoing. RESULTS/ANTICIPATED RESULTS: Initial analysis indicate all tumors exhibited higher overall uptake of [89 Zr]trastuzumab across various sites including the bone (p=0.019), brain (p=0.014), and breast (p=0.069), when compared to corresponding normal organs. Additionally, increased ADCmean values were observed in all regions besides brain tumors (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), indicating distinct patterns of cellularity. Notably, one of five patients with a breast lesion, who exhibited a complete response to HER2-targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Qualification of multi parametric maps is anticipated to inform on intratumoral heterogeneity DISCUSSION/SIGNIFICANCE: Despite limitation in clinical applications of quantitative approaches due to lack of standardization of processing, initial investigations, in combining molecular imaging of HER2 and quantitative MRI demonstrate potential in characterizing metastatic HER2+ breast cancer for intratumoral classification and therapeutic stratification.

Loss of methylthioadenosine phosphorylase immunoreactivity correlates with poor prognosis and elevated uptake of 11C-methionine in IDH-mutant astrocytoma.

The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88years vs. 6.80years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23years vs. 10.69years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

Second generation Al18F-labeled D-amino acid peptide for CXCR4 targeted molecular imaging

BackgroundThe C-X-C chemokine receptor type 4 (CXCR4) is overexpressed in many cancers, e.g. multiple myeloma and acute leukemia, yet solely [68Ga]PentixaFor is used for clinical PET imaging. The aim of this study was to develop and assess a second generation Al18F-labeled D-amino acid peptide based on the viral macrophage inflammatory protein II for CXCR4 targeted molecular imaging. MethodsWe designed a library of monomer and multimer constructs and evaluated their binding affinity for human and mouse CXCR4. Based on these results, we selected the best vector molecule for development of an Al18F-labeled ligand, [18F]AlF-NOTA-2xDV1(c11sc12s), which was further evaluated in a cell-based binding assay to assess its binding properties and specificity for CXCR4. Next, pharmacokinetics and tumor uptake of [18F]AlF-NOTA-2xDV1(c11sc12s) were evaluated in naïve mice and mice with xenografts derived from U87.CXCR4 cells. Finally, we performed an imaging study in a non-human primate to assess the in vivo distribution of this novel radioligand in a species closely related to humans. ResultsThe lead ligand AlF-NOTA-2xDV1(c11sc12s) showed six-fold higher affinity for human CXCR4 compared to Ga-Pentixafor. The corresponding radiotracer was obtained in a good radiochemical yield of 40.1 ± 13.5 % (n = 4) and apparent molar activity of 20.4 ± 3.3 MBq/nmol (n = 4) after optimization. In U87.CD4.CXCR4 cell binding assays, the total bound fraction of [18F]AlF-NOTA-(2×)DV1(c11sc12s) was 32.4 ± 1.8 %. This fraction could be reduced by 82.5 % in the presence of 75 μM AMD3100. In naïve mice, [18F]AlF-NOTA-2xDV1(c11sc12s) accumulated in organs expressing mouse CXCR4, e.g. the liver (SUVmean (mean standardized uptake value) 75 min p.i. 11.7 ± 0.6), which was blockable by co-injecting AMD3100 (5 mg/kg). In U87.CXCR4 xenografted tumor mice, the tumor uptake of [18F]AlF-NOTA-2xDV1(c11sc12s) remained low (SUVmean 0.5 ± 0.1), but was reduced by co-administration of AMD3100. Surprisingly, [18F]AlF-NOTA-2xDV1(c11sc12s) exhibited a similar biodistribution in a non-human primate as in mice indicating off-target binding of [18F]AlF-NOTA-2xDV1(c11sc12s) in liver tissue. We confirmed that [18F]AlF-NOTA-2xDV1(c11sc12s) is taken up by hepatocytes using in vitro studies and that the uptake can be blocked with AMD3100 and rifampicin, a potent organic anion-transporting-polypeptide (OATP)1B1 and OATP1B3 inhibitor. ConclusionThe second generation D-peptide AlF-NOTA-2xDV1(c11sc12s) showed high affinity for human CXCR4 and the corresponding radiotracer was produced in good radiochemical yields. However, [18F]AlF-NOTA-2xDV1(c11sc12s) is not specific for CXCR4 and is also a substrate for OATP1B1 and/or OATP1B3, known to mediate hepatic uptake. Therefore, D-amino acid peptides, based on the viral macrophage inflammatory protein II, are not the prefered vector molecule for the development of CXCR4 targeting molecular imaging tools.

Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma.

Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans.