EJNMMI Research最新文献

Background: Body composition (BC) analysis is performed to quantify the relative amounts of different body tissues as a measure of physical fitness and tumor cachexia. We hypothesized that relative changes in body composition (BC) parameters, assessed by an artificial intelligence-based, PACS-integrated software, between baseline imaging before the start of radioligand therapy (RLT) and interim staging after two RLT cycles could predict overall survival (OS) in patients with metastatic castration-resistant prostate cancer.

Methods: We conducted a single-center, retrospective analysis of 92 patients with mCRPC undergoing [¹⁷⁷Lu]Lu-PSMA RLT between September 2015 and December 2023. All patients had [⁶⁸ Ga]Ga-PSMA-11 PET/CT at baseline (≤ 6 weeks before the first RLT cycle) and at interim staging (6-8 weeks after the second RLT cycle) allowing for longitudinal BC assessment.

Results: During follow-up, 78 patients (85%) died. Median OS was 16.3 months. Median follow-up time in survivors was 25.6 months. The 1 year mortality rate was 32.6% (95%CI 23.0-42.2%) and the 5 year mortality rate was 92.9% (95%CI 85.8-100.0%). In multivariable regression, relative change in visceral adipose tissue (VAT) (HR: 0.26; p = 0.006), previous chemotherapy of any type (HR: 2.4; p = 0.003), the presence of liver metastases (HR: 2.4; p = 0.018) and a higher baseline De Ritis ratio (HR: 1.4; p < 0.001) remained independent predictors of OS. Patients with a higher decrease in VAT (< -20%) had a median OS of 10.2 months versus 18.5 months in patients with a lower VAT decrease or VAT increase (≥ -20%) (log-rank test: p = 0.008). In a separate Cox model, the change in VAT predicted OS (p = 0.005) independent of the best PSA response after 1-2 RLT cycles (p = 0.09), and there was no interaction between the two (p = 0.09).

Conclusions: PACS-Integrated, AI-based BC monitoring detects relative changes in the VAT, Which was an independent predictor of shorter OS in our population of patients undergoing RLT.

Background: For patients diagnosed with primary aldosteronism (PA) accompanied by bilateral adrenal lesions, identifying optimal candidates for surgical intervention remains a significant clinical challenge. Although adrenal venous sampling (AVS) is currently the gold standard for lateralizing aldosterone hypersecretion, its technical complexity, invasiveness, and interpretive difficulties restrict its widespread adoption. In this study, we aimed to investigate the clinical application of ⁶⁸Ga-pentixafor positron emission tomography/computed tomography (PET/CT) as a non-invasive imaging modality in AVS-free surgical decision-making for PA patients with bilateral adrenal lesions.

Results: Among the 51 patients who underwent ⁶⁸Ga-pentixafor PET/CT, 36 patients had adrenalectomy, with the surgical side determined by PET/CT lateralization. The postoperative complete biochemical and clinical success rates for these patients were 91.67% and 100%, respectively. Additionally, receiver operating characteristic curve analysis indicated that PET/CT results were favorable predictors of postoperative outcomes in surgical patients. Postoperative pathological evaluation of ⁶⁸Ga-pentixafor PET/CT-guided surgical patients revealed that 86.11% had adrenocortical adenomas with positive CYP11B2 and CXCR4 expression.

Conclusion: CXCR4-targeted ⁶⁸Ga-pentixafor PET/CT can be effectively utilized in surgery decision-making for PA patients with bilateral adrenal lesions, offering a potential alternative to AVS and maybe applied to predict postoperative biochemical and clinical success.

Trial registration: ⁶⁸Ga-Pentixafor PET/CT for Guiding Surgical Treatment of Primary Aldosteronism With Bilateral Adrenal Lesions; Trial registration number: NCT06247566; Date of registration: 2021-11-01; URL of trial registry record: https://clinicaltrials.gov/study/NCT06247566 .

Background: Assessment of glucose uptake by PET imaging under hyperinsulinemic euglycemic clamp (HEC) is an insightful tool for quantification of insulin resistance, a hallmark of diabetes and an area of interest in drug development. To enable the use of the method in metabolic trials, the repeatability of dynamic whole-body PET/MRI assessments of the tissue-specific glucose uptake and the total body glucose utilisation were investigated. The study included participants with type 2 diabetes mellitus (T2DM) and overweight/obesity, for two repeated examinations in standardised conditions. All participants signed informed consent, and the study plan was approved by the Swedish Ethical Review Authority (#2020-04140). After an overnight fast, HEC was established and a series of [¹⁸F]FDG-PET/MRI scans were performed. Total body glucose utilisation (M-value) was calculated for the duration of the scan and the tissue-specific metabolic rates of glucose uptake (MRGlu) were calculated using Patlak model. The repeatability was assessed by calculating the intraclass correlation coefficient (ICC).

Results: Repeatability was assessed in per protocol set of 12 participants (PPS, defined by a consistent HEC) and in full analysis set (FAS n = 16). The measured M-values and tissue MRGlu demonstrated varying levels of insulin resistance. M-value ICC was 0.95 (95% CI 0.86-0.99) for PPS, indicating excellent repeatability. Tissue-specific MRGlu repeatability was excellent for skeletal muscle (ICC 0.94), and good to at least fair for SAT, VAT, myocardium, and brain. The FAS had lower, but at least fair repeatability, emphasising the importance of standardisation in metabolic assessments.

Conclusion: Dynamic [¹⁸F]FDG-PET/MRI provides quantitative information on tissue-specific insulin sensitivity during hyperinsulinemic euglycemic clamp with a reliability comparable to total body glucose utilisation assessment. The method has potential to add value in monitoring and evaluating T2DM treatment effects on glucose uptake and insulin resistance in interventional trials.

Background: Gastrin-releasing peptide receptor (GRPR) is overexpressed in several cancers, including prostate and breast, making it an attractive target for radiopharmaceutical development. Studies on GRPR-targeting radioligands highlight the critical role of the spacer region between the GRPR-recognition motif and radiolabeled moiety, which can significantly influence peptide pharmacokinetics and pharmacodynamics. Herein, we investigated the impact of structurally restricted spacers on the performance of RM26-based radioligands.

Results: Three novel radioligands were designed to each bear a NOTA chelator via different spacers composed of N-acetyl-lysine followed by either o-ethyltoluene (oET), o-methylanisole (oMA), or m-methylanisole (mMA) motifs. The peptides were successfully labeled with Ga-68, achieving high radiochemical yield, purity, and molar activity. The resulting [⁶⁸Ga]-labeled peptides demonstrated high and GRPR-specific binding to prostate cancer PC-3 cells, antagonistic behavior, and the IC₅₀ values to GRPR were in the single-digit nanomolar range. Biodistribution studies at 2 h post-injection in PC-3 xenograft-bearing mice revealed high, GRPR-mediated tumor uptake for all three radioligands. In addition, high hepatobiliary excretion with elevated uptake in the liver and the gastrointestinal tract and pronounced pancreatic uptake were observed.

Conclusions: Among the three radioligands, the peptide bearing the N-acetyl-lysine-oET spacer exhibited the fastest background clearance and better PET imaging of prostate cancer xenografts. The incorporation of conformationally restricted spacers is a promising strategy for developing tracers with high GRPR binding and good imaging properties, but further optimization is necessary to reduce uptake in healthy tissues.

Background: Severe cerebrovascular events are associated with carotid atherosclerotic plaque progression and rupture that is mediated by inflammation. ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) PET is important for assessing the inflammation of carotid atherosclerotic plaque, but it suffers from the limitations of radiation exposure. Additionally, inflammation of perivascular adipose tissue (PVAT) has been found to promote atherosclerosis progression through paracrine signaling mechanisms. The study aimed to develop an ensemble model based on carotid plaque and PVAT MRI radiomics for identifying highly inflammatory plaques (HIPs).

Results: 159 asymptomatic carotid atherosclerosis patients (137 males; 65 ± 8 years old) with 209 plaques (104 HIPs) were consecutively enrolled. 47.95% (70/146) of cases and 53.97% (34/63) were defined as HIPs in the training and testing datasets, respectively. There was more lipid core, more intraplaque hemorrhage, and less calcification in the HIPs compared to the non-highly inflammatory plaques (NHIPs) in the training dataset (p = 0.002, 0.019, and 0.013, respectively). Notably, the incidence of indistinct PVAT (IPVAT) in HIPs was higher than that in NHIPs, both in the training (81.43% vs. 46.05%; p < 0.001) and the testing (88.24% vs. 58.62%; p = 0.007) datasets. The correlations between plaque MRI characteristics and [¹⁸F]FDG uptake differed between the NHIPs and HIPs. However, IPVAT consistently correlated with SUV_max (r = 0.35, 0.30; p < 0.001, p = 0.002; for NHIPs and HIPs, respectively). The ensemble model that integrates the radiomics of carotid plaque and PVAT outperformed all models in predicting HIP (area under the curve [AUC] = 0.92/0.91, training/testing dataset). The follow-up further validated the PET for predicting plaque progression with the same accuracy as the ensemble model (AUC: 0.85 vs. 0.79).

Conclusions: The ensemble model integrating the radiomics of carotid plaque and perivascular adipose tissue provides an equivalent tool to PET in the visualization of the evaluation of carotid atherosclerosis inflammation and progression.