Positron Emission Research Articles

Which patients with negative PSMA-PET imaging can safely avoid biopsy for prostate cancer? a novel step towards PSMA-based biopsy-free strategy.

This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET). Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations. Clinically significant prostate cancer (csPCa) was defined as Grade Group ≥ 2. Multivariate logistic regression was employed to identify predictors of non-csPCa. Receiver operating characteristic (ROC) analysis was performed to detect non-csPCa on prostate pathology. PSMA-postive patients were additionally reviewed to assess the imaging and pathological outcomes. Younger age was identified as an independent predictor (P = 0.006) for the absence of csPCa. ROC analysis of csPCa revealed the largest areas under the curve of 0.77 (0.67-0.87) and 0.78 (0.68-0.88) for individual age in the entire PSMA-negative cohort and the MRI subset, respectively (both P < 0.001). The negative predictive value (NPV) of PSMA-PET for csPCa detection improved with a decreasing age, from 88% in all, to 98% in men aged under 65 yrs (98% vs. 88%, P = 0.021), and to 100% in men aged under 60 yrs (100% vs. 88%, P = 0.040). The NPV of PSMA-PET improved from 88 to 94% when combined with negative MRI, and to 100% in men with negative MRI and aged under 65 yrs. The prevalence was 57% for csPCa and 65% for PCa of any grade. We preliminarily propose that omission or postponement of prostate biopsy should be considered for men under the age of 65 yrs with negative PSMA-PET scored as PRIMARY 1 or 2. Conversely, prostate biopsy might be considered in biopsy-naïve men aged 65 yrs or older with strong clinical suspicion of PCa, despite negative PSMA-PET. Further prospective and external evaluation is needed to prove the robustness of this novel strategy.

Flurpiridaz F 18: First Approval.

Flurpiridaz F 18 (FLYRCADO™) is an intravenous (IV) radioactive diagnostic drug being developed by GE Healthcare and Lantheus Medical Imaging for use in positron emission tomography (PET) myocardial perfusion imaging (MPI) to detect coronary artery disease (CAD). In September 2024, flurpiridaz F 18 was approved in the USA for PET MPI under rest or stress (pharmacologic or exercise) in adult patients with known or suspected CAD to evaluate for myocardial ischemia and infarction. This article summarizes the milestones in the development of flurpiridaz F 18 leading to this first approval for use in PET MPI in adult patients to evaluate for myocardial ischemia and infarction.

Quantitative and Visual Benefits of Data-Driven Motion Correction on Oncologic PET/CT: AProspective Cross-sectional Study.

Conventional positron emission tomography (PET) respiratory gating utilizes a fraction of acquired PET counts (i.e., optimal gate [OG]), whereas elastic motion correction with deblurring (EMCD) utilizes all PET counts to reconstruct motion-corrected images without increasing image noise. Our aim was to assess the quantitative and visual impacts of EMCD-based motion correction on FDG-PET and DOTATATE-PET images relative to OG and ungated (UG) images. This prospective, single-center study enrolled adults undergoing FDG or DOTATATE oncologic PET/CT between June 2020 and October 2022. Subjects underwent a standard-of-care (SOC) PET acquisition while wearing a respiratory gating belt. UG, belt-gating-derived optimal gate (BG-OG), EMCD utilizing belt gating (BG-EMCD), and EMCD utilizing data-driven gating (DDG-EMCD) images were reconstructed. Tracer-avid lesions in the lower chest or upper abdomen were segmented. Quantitative metrics were extracted. Two independent, blinded readers assessed image quality via a 4-point scale and counted lesions on each reconstruction. Differences between reconstructions were assessed via the Wilcoxon signed-rank test (alpha, 0.05). This study enrolled 78 subjects; 36 subjects (mean age, 64.8 years; 20 males) with 136 tracer-avid lesions were analyzed. Data provided are medians across all tracers. Lesion SUV-max was significantly higher (P<0.001) on motion-corrected images (BG-OG: 10.77, BG-EMCD: 10.75, DDG-EMCD: 10.74) than UG images (9.00). Lesion contrast-to-noise ratios (CNRs) were significantly lower (P<0.001) for BG-OG (6.31) and UG images (7.89) than BG-EMCD (9.14) and DDG-EMCD (8.89) images. FDG and DOTATATE subgroup analyses produced similar results. Among motion-corrected images, both readers preferred EMCD-based images to BG-OG images for all tracers (P<0.001) and both subgroups. EMCD-based images occasionally demonstrated more tracer-avid lesions than BG-OG or UG images. EMCD-based motion correction beneficially impacts lesion quantitation (including higher SUVs and CNRs) and overall image quality. When employed on capable scanners, EMCD can improve the quality of oncologic PET imaging.

Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.

Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification. We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRSno APOE), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls. Together AD-PRSno APOE and APOE-RS performed similarly to p-tau181 in discriminating MCI+/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, Aβ positivity was significantly associated with APOE-RS, but not with AD-PRSno APOE, or p-tau181. Combining AD-PRSno APOE, APOE-RS, and p-tau181 improved thediscrimination of MCI+/AD from controls (81%) and LBD (75%), and thedetection of Aβ in LBD (82%). Aβ deposition in LBD was associated with APOE, while MCI+/AD was also associated with AD-PRS beyond APOE. AD-PRS explains phenotypic variance not captured by APOE or p-tau181. We investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (APOE), and plasma phosphorylated tau 181 (p-tau181) to classify AD and Lewy body dementia (LBD). AD-PRS with APOE achieved similar classification accuracy to p-tau181. AD-PRS without APOE significantly contributed to discriminating AD from LBD. Amyloid beta positivity in LBD was associated with APOE but not AD-PRS without APOE or p-tau181. Combining AD-PRS, APOE, and p-tau181 improved diagnostic classification accuracy.

Altered brain glucose metabolism in COVID-19 disease: an activation likelihood estimation meta-analysis of PET studies.

COVID-19 disease, caused by the SARS-CoV-2 virus, has significantly altered modern society and lifestyles. We investigated its impact on brain glucose metabolism by meta-analyzing existing studies that utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans of the brain. We conducted a systematic search of MEDLINE and EMBASE databases from inception to August 2024 for English-language publications using the keywords "positron emission tomography", and "COVID-19". We included original research articles that reported changes in brain glucose metabolism following COVID-19 disease. ALE values from these studies were aggregated and tested against a null hypothesis that anticipated a random distribution of ALE values, which proved to be significantly higher than chance. We identified nine papers that met our inclusion criteria. Significant increases in brain glucose metabolism were noted in the left anterior cingulate gyrus, right thalamus, and brainstem. In children with COVID-19 disease, decreased glucose metabolism was observed in the right and left cerebellum, left amygdala/hippocampus, left anterior cingulate gyrus, and right amygdala. In adults with COVID-19 disease, decreased metabolism was seen in the right temporal lobe, brainstem (acute phase), left occipital lobe, left and right temporal lobe (chronic phase). In conclusion, COVID-19 disease impacts brain glucose metabolism, typically manifesting as areas of decreased metabolism in 18F-FDG PET scans, though increases are also observed. These changes in metabolism vary with the patient's age and the time elapsed between the diagnosis of COVID-19 disease and the PET scan.

Realistic total-body J-PET geometry optimization: Monte Carlo study.

Total-body (TB) Positron Emission Tomography (PET) is one of the most promising medical diagnostics modalities, opening new perspectives for personalized medicine, low-dose imaging, multi-organ dynamic imaging or kinetic modeling. The high sensitivity provided by total-body technology can be advantageous for novel tomography methods like positronium imaging, demanding the registration of triple coincidences. Currently, state-of-the-art PET scanners use inorganic scintillators. However, the high acquisition cost reduces the accessibility of TB PET technology. Several efforts are ongoing to mitigate this problem. Among the alternatives, the Jagiellonian PET (J-PET) technology, based on axially arranged plastic scintillator strips, offers a low-cost alternative solution for TBPET. The work aimed to compare five total-body J-PET geometries with plastic scintillators suitable for multi-organ and positronium tomography as a possible next-generation J-PET scannerdesign. We present comparative studies of performance characteristics of the cost-effective total-body PET scanners using J-PET technology. We investigated in silico five TB scanner geometries, varying the number of rings, scanner radii, and other parameters. Monte Carlo simulations of the anthropomorphic XCAT phantom, the extended 2-m sensitivity line source and positronium sensitivity phantoms were used to assess the performance of the geometries. Two hot spheres were placed in the lungs and in the liver of the XCAT phantom to mimic the pathological changes. We compared the sensitivity profiles and performed quantitative analysis of the reconstructed images by using quality metrics such as contrast recovery coefficient, background variability and root mean squared error. The studies are complemented by the determination of sensitivity for the positronium lifetime tomography and the relative cost analysis of the studiedsetups. The analysis of the reconstructed XCAT images reveals the superiority of the seven-ring scanners over the three-ring setups. However, the three-ring scanners would be approximately 2-3 times cheaper. The peak sensitivity values for two-gamma vary from 20 to 34cps/kBq and are dominated by the differences in geometrical acceptance of the scanners. The sensitivity curves for the positronium tomography have a similar shape to the two-gamma sensitivity profiles. The peak values are lower compared to the two-gamma cases, from about 20-28 times, with a maximum value of 1.66 cps/kBq. This can be contrasted with the 50-cm one-layer J-PET modular scanner used to perform the first in-vivo positronium imaging with a sensitivity of 0.06 cps/kBq. The results show the feasibility of multi-organ imaging of all the systems to be considered for the next generation of TB J-PET designs. Among the scanner parameters, the most important ones are related to the axial field-of-view coverage. The two-gamma sensitivity and XCAT image reconstruction analyzes show the advantage of seven-ring scanners. However, the cost of the scintillator materials and SiPMs is more than two times higher for the longer modalities compared to the three-ring solutions. Nevertheless, the relative cost for all the scanners is about 10-4 times lower compared to the cost of the uExplorer. These properties coupled together with J-PET cost-effectiveness and triggerless acquisition mode enabling three-gamma positronium imaging, make the J-PET technology an attractive solution for broad application inclinics.

The prognostic value of baseline EARL standardized FDG PET indices in pediatric and adolescent high-grade osteosarcoma.

To investigate the prognostic value of baseline European Association of Nuclear Medicine Research Ltd. (EARL) standardized [18F]fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG PET-CT) quantitative values for survival and to evaluate cutoff values identified in other studies. Pediatric and adolescent patients with high-grade osteosarcoma were included. Baseline [18F]FDG PET-CT, with EARL-accredited reconstructions, was the standard diagnostic staging procedure. Cox proportional hazard analysis for event-free survival (EFS) and overall survival (OS) was performed with clinical prognostic factors. Kaplan-Meier analysis and log-rank tests were applied to investigate the prognostic performance of the [18F]FDG PET indices. In total, 66 patients were included in this study. In the univariable Cox regression analysis, peak lean-body mass corrected SUV (SULpeak) (hazard ratio (HR): 1.04), total lesion glycolysis (TLG) (HR: 1.0), and metabolic tumor volume (MTV) (HR: 1.0) were not associated with EFS or OS. Log-rank analysis showed a significant difference in EFS for all SULmax and SULpeak cutoffs. For MTVtotal the maximum Youden, and for TLGtotal, the maximum Youden and maximally selected rank cutoff resulted in a significant EFS difference. No cutoff for any measure showed a significant difference in OS between the groups. ROC curves for event status had an AUC of 0.67, 0.66, 0.64, and 0.64 for SULmax, SULpeak, MTVtotal, and TLGtotal, respectively. In this study, the baseline EARL-standardized [18F]FDG PET indices of children and adolescents with osteosarcoma were not prognostic of EFS or OS. The proposed prognostic cutoffs from earlier studies suffer from important technical and statistical issues. Question Prognostic value of baseline [18F]FDG PET-CT imaging markers have been reported for histologic response and survival in high-grade osteosarcoma but have not been validated for clinical practice. Findings Baseline SUVpeak, TLGtotal, and MTVtotal measured on EARL-accredited reconstructions were not prognostic factors for survival in pediatric and adolescent patients with high-grade osteosarcoma. Clinical relevance A wide range of values for SUVpeak and SUVmax cutoffs with similar prognostic value were identified, questioning the value of a single proposed cutoff. Lack of validation, with important technical and statistical issues of proposed prognostic cutoffs, limits clinical implementation.

Discordance between prostate MRI and PSMA-PET/CT: the next big challenge for primary prostate tumor assessment?

An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of discordance between MRI and PSMA-PET/CT for primary PCa assessment. Consecutive men diagnosed with intermediate and high-risk PCa who underwent MRI and PSMA-PET/CT in 2021-2023 were retrospectively included. MRI and PSMA-PET/CT were interpreted using PI-RADS v2.1 and PRIMARY scores. Discordances between the two imaging modalities were categorized as "minor" (larger or additional lesion seen on one modality) or "major" (positive on only one modality or different index lesions between MRI and PSMA-PET/CT) and reconciled using radical prostatectomy or biopsy specimens. Three hundred and nine men (median age 69 years, interquartile range (IQR) 64-75) were included. Most had Gleason Grade Group ≥ 3 PCa (70.9% (219/309)). Median PSA was 9.0 ng/mL (IQR 5.6-13.6). MRI and PSMA-PET/CT were concordant in 157/309 (50.8%) and discordant in 152/309 (49.1%) patients; with 39/152 (25.7%) major and 113/152 (74.3%) minor discordances. Of 27 patients with lesions only seen on MRI, 85.2% (23/27) were clinically significant PCa (csPCa). Of 23 patients with lesions only seen on PSMA-PET/CT, 78.3% (18/23) were csPCa. Altogether, lesions seen on only one modality were csPCa in 80.0% (36/45). MRI and PSMA-PET/CT were discordant in half of patients for primary PCa evaluation, with major discrepancies seen in roughly one out of eight patients. Question While both MRI and PSMA-PET/CT can be used for primary tumor assessment, the discordances between them are not well established. Findings MRI and PSMA-PET/CT were discordant in about half of the patients. Most prostate lesions seen on only one modality were significant cancer. Clinical relevance MRI and PSMA-PET/CT are often discordant for assessing the primary prostate tumor. Using both modalities for primary prostate tumor evaluation can provide complementary information that may substantially impact treatment planning.

Educational attainment, Aβ, tau, and structural brain reserve in Alzheimer's disease.

Alzheimer's disease (AD) patients with higher educational attainment (EA) often exhibit better cognitive function. However, the relationship among EA status, AD pathology, structural brain reserve, and cognitive decline requires further investigation. We compared cognitive performance across different amyloid beta (Aβ) positron emission tomography (A±) statuses and EA levels (High EA/Low EA). We examined the effects of Aβ plaques, tau tangles, and gray matter volume (GMV) on the relationship between EA and domain-specific cognitive decline. A+/High-EA individuals exhibited slower cognitive decline in global cognition and language domains than A+/Low-EA individuals. This cognitive benefit was independently and synergistically explained by reduced AD pathology, including lower Aβ and tau burdens, as well as preserved GMV. Additionally, High-EA individuals experienced a median delay of 1.9 years in the onset of significant brain atrophy among A+ individuals. These findings highlight the independent and synergistic contributions of EA-associated AD pathology and GMV alterations to longitudinal cognitive decline. Alzheimer's disease (AD) individuals with high educational attainment (EA) show slower declines in global cognition and language. EA-related slower cognitive decline is linked to reduced tau and greater gray matter volume in AD. AD individuals with high EA show a median 1.9 year delayed onset of brain atrophy.

Who is a candidate at the initial presentation? Prediction of positive lateral lymph node and survival after dissection.

Metastatic lateral pelvic lymph node (LPN) in rectal cancer has a significant clinical impact on the prognosis and treatment strategies. But there are still debates regarding prediction of lateral pelvic lymph node metastasis and its oncological impact. This review explores the evidence for predicting lateral pelvic lymph node metastasis and survival in locally advanced rectal cancer. Until now many studies have reported that magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) are considered as essential tools for predicting metastatic LPN, with MRI-based size criteria, particularly the short-axis diameter of LPN. But several studies have reported that the addition of tumor location or artificial intelligence (AI) can further enhance diagnostic accuracy. Western practices focus more on neoadjuvant chemoradiation (nCRT), while Eastern countries focus more on lateral pelvic lymph node dissection (LPND). LPND has been shown to reduce lateral local recurrence (LLR) rates compared to total mesorectal excision (TME) alone, particularly in patients with enlarged LPNs, but its impact on overall survival is uncertain. The decision to perform LPND should be individualized according to LPN size and response to nCRT; and through selective LPND based on those criteria, patients could achieve a balance between the benefit of local control and the risk of surgical complications from LPND, such as sexual and urinary dysfunction.

Non-parametric Bayesian deep learning approach for whole-body low-dose PET reconstruction and uncertainty assessment.

Positron emission tomography (PET) imaging plays a pivotal role in oncology for the early detection of metastatic tumors and response to therapy assessment due to its high sensitivity compared to anatomical imaging modalities. The balance between image quality and radiation exposure is critical, as reducing the administered dose results in a lower signal-to-noise ratio (SNR) and information loss, which may significantly affect clinical diagnosis. Deep learning (DL) algorithms have recently made significant progress in low-dose (LD) PET reconstruction. Nevertheless, a successful clinical application requires a thorough evaluation of uncertainty to ensure informed clinical judgment. We propose NPB-LDPET, a DL-based non-parametric Bayesian framework for LD PET reconstruction and uncertainty assessment. Our framework utilizes an Adam optimizer with stochastic gradient Langevin dynamics (SGLD) to sample from the underlying posterior distribution. We employed the Ultra-low-dose PET Challenge dataset to assess our framework's performance relative to the Monte Carlo dropout benchmark. We evaluated global reconstruction accuracy utilizing SSIM, PSNR, and NRMSE, local lesion conspicuity using mean absolute error (MAE) and local contrast, and the clinical relevance of uncertainty maps employing correlation between the uncertainty measures and the dose reduction factor (DRF). Our NPB-LDPET reconstruction method exhibits a significantly superior global reconstruction accuracy for various DRFs (paired t-test, , N=10,631). Moreover, we demonstrate a 21% reduction in MAE (573.54 vs. 723.70, paired t-test, , N=28) and an 8.3% improvement in local lesion contrast (2.077 vs. 1.916, paired t-test, , N=28). Furthermore, our framework exhibits a stronger correlation between the predicted uncertainty 95th percentile score and the DRF ( vs. , N=10,631). The proposed framework has the potential to improve clinical decision-making for LD PET imaging by providing a more accurate and informative reconstruction while reducing radiation exposure.

A Comprehensive Review on the Application of Artificial Intelligence for Predicting Postsurgical Recurrence Risk in Early-Stage Non-Small Cell Lung Cancer Using Computed Tomography, Positron Emission Tomography, and Clinical Data.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Despite advancements in early detection and treatment, postsurgical recurrence remains a significant challenge, occurring in 30%-55% of patients within 5 years after surgery. This review analysed existing studies on the utilisation of artificial intelligence (AI), incorporating CT, PET, and clinical data, for predicting recurrence risk in early-stage NSCLCs. A literature search was conducted across multiple databases, focusing on studies published between 2018 and 2024 that employed radiomics, machine learning, and deep learning based on preoperative positron emission tomography (PET), computed tomography (CT), and PET/CT, with or without clinical data integration. Sixteen studies met the inclusion criteria and were assessed for methodological quality using the METhodological RadiomICs Score (METRICS). The reviewed studies demonstrated the potential of radiomics and AI models in predicting postoperative recurrence risk. Various approaches showed promising results, including handcrafted radiomics features, deep learning models, and multimodal models combining different imaging modalities with clinical data. However, several challenges and limitations were identified, such as small sample sizes, lack of external validation, interpretability issues, and the need for effective multimodal imaging techniques. Future research should focus on conducting larger, prospective, multicentre studies, improving data integration and interpretability, enhancing the fusion of imaging modalities, assessing clinical utility, standardising methodologies, and fostering collaboration among researchers and institutions. Addressing these aspects will advance the development of robust and generalizable AI models for predicting postsurgical recurrence risk in early-stage NSCLC, ultimately improving patient care and outcomes.

Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis.

Actinium-225 labeled prostate-specific membrane antigen (PSMA) targeted radionuclide therapy has emerged as a potential treatment option in the management of men with metastatic castrate-resistant prostate cancer (mCRPC). This study investigated molecular imaging-derived parameters and compared imaging response of lesions categorized by tumor site. Men with mCRPC treated with [225Ac]Ac-J591 from 2017 to 2022 at our center on two prospective trials (NCT03276572 and NCT04506567) with pre- and post-treatment [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET) imaging studies available were included. SUVpeak of the 3 most- and 3 least-avid lesions of the tumor sites were manually assessed. The median change of the SUVpeak from pre- to post-treatment per tumor site was evaluated using the paired Wilcox test. An objective response (OR) in the follow-up image was defined as complete or partial response using PET Response Criteria in Solid Tumors (PERCIST) 1.0. A total of 46 cases met the criteria for image review; most of them (n = 25, 54.3%) had more than one tumor site category. In total, 445 PSMA PET-positive lesions were assessed: 220 osseous, 163 nodal, 41 visceral, and 21 prostatic lesions. After treatment with [225Ac]Ac-J591, absolute SUVpeak values per tumor site declined significantly (p < 0.05) except for prostatic lesions (p = 1). The PERCIST-OR rate for osseous, nodal, visceral, and prostatic lesions was 53%, 28%, 56%, and 38%, respectively. [225Ac]Ac-J591 is an active treatment in men with mCRPC. Tumor distribution patterns may influence treatment response and potentially prognosis. Our findings warrant further validation in a larger cohort but may be considered in treatment planning and trial design.

Rare Rib-Originating Solitary Plasmacytoma: Retrospective Analysis and Surgical Outcomes.

Solitary plasmacytomas are tumors characterized by a local increase of malignant plasma cells in soft tissue or bone and may occur anywhere without evidence of systemic disease. The aim was to focus on the main surgical techniques and outcomes for this rare chest wall tumor. Patients with solitary plasmacytoma involving a rib, who were operated for diagnostic or treatment purposes between 2018 and 2023 were retrospectively reviewed. Of the six patients included, three were male and the median age was 55.6 (range: 32-74) ys. All patients had preoperative positron emission tomography-computed tomography. Two underwent Tru-cut biopsy before surgery, but only one was then diagnosed. Two patients underwent surgery for diagnosis and the remainder underwent resection and reconstruction. In one patient with both rib and sternum involvement, rib and partial sternum resection was performed and the defect was repaired with mesh. During the 24.1mos average follow-up period, two patients died, both of whom had metastasis preoperatively. The median survival of all patients was 24.1 (range: 3-63) mos. Solitary plasmacytoma is rarely seen among primary malign tumors of the chest wall. A multidisciplinary approach is important in these cases. Surgical treatment in solitary plasmacytoma has fewer local and systemic side effects compared to radiotherapy and chemotherapy. Therefore, the place of surgery in the treatment of solitary plasmacytoma should be revised. Our findings show that surgery should be considered as not only a palliative treatment, but also a curative one, in solitary plasmacytomas arising in the rib.

Diagnostic Value of Gastrin-Releasing Peptide Receptor-Targeted PET Imaging in Oncology: A Systematic Review.

Gastrin-releasing peptide receptor (GRPR), overexpressed in various cancers, is a promising target for positron emission tomography (PET). This systematic review investigated the diagnostic value of GRPR-targeted PET imaging in oncology. A systematic search was conducted on major medical databases until May 23, 2024. Keywords were modified to include clinical original studies on GRPR-targeted PET in cancer patients. Out of 1624 searched studies initially, 107 were eligible for the full-text review. Overall, data from 38 studies met inclusion criteria, investigating GRPR-targeting radiotracers in breast cancer, prostate cancer, gastrointestinal stromal tumours (GIST) and gliomas (including optic pathway glioma and glioblastoma multiforme). In breast cancer, GRPR-targeted PET effectively detected primary tumours and metastases, particularly in estrogen receptor (ER)-positive patients, and predicted treatment response. In prostate cancer, high sensitivity (up to 88%) and specificity (up to 90%) for detecting primary tumours were observed, providing added value when combined with magnetic resonance imaging (MRI). In biochemical recurrence, sites of prostate cancer were identified even at PSA levels below 0.5ng/dL. Compared with PSMA PET, GRPR-targeted PET showed comparable or superior detection rates. Considering GIST, GRPR-targeted PET imaging proved to be a valuable diagnostic tool, particularly when [18F] FDG PET results were inconclusive. Regarding gliomas, GRPR-targeted PET achieved a 100% detection rate (MRI reference), aiding localization, preoperative planning, and differentiation between recurrence and malignant transformation. GRPR-targeted PET shows promise in improving cancer diagnostics, particularly in ER-positive breast cancer, prostate cancer, and gliomas, and may enhance clinical decision-making.

177Lu-Labeled Heterodimeric Agent with High Stability Targeting Neovascularization for Tumor Radioligand Therapy.

Radiopharmaceutical theranostics holds significant promise in tumor diagnosis and treatment, but suboptimal tumor uptake and retention remain a persistent limitation. We have conjugated a unique albumin binder to our previously developed heterodimeric precursor HX01 and achieved a novel precursor L6, aiming to prolong circulation time and enhance tumor accumulation and retention. However, we observed that the NGR sequence of L6 was gradually rearranged to iso-DGR under alkaline conditions, resulting in decreased stability. In this study, we further modified the L6 to synthesize XH02, subsequently assessing their in vitro and in vivo properties following radiolabeling. Utilizing positron emission tomography (PET)/computed tomography (CT) imaging, single-photon emission computed tomography (SPECT)/CT imaging, and biodistribution study in BxPC-3 xenograft mice, we observed striking accumulation and retention of radiopharmaceutical within tumors. Two cycles of administration of 177Lu-XH02 displayed exceptional tumor growth inhibition in BxPC-3 tumors while causing minimal side effects. This promising result underscores the immense potential of this agent for further clinical translation and investigation.

Prognostic 18F-flotufolastat PET parameters for outcome assessment of 177Lu-labeled PSMA-targeted radioligand therapy in metastatic castration-resistant prostate cancer.

This retrospective analysis evaluates baseline 18F-flotufolastat positron emission tomography (PET) parameters as prognostic parameters for treatment response and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with [177Lu]Lu-PSMA-I&T. A total of 188 mCRPC patients with baseline 18F-flotufolastat PET scans were included. Tumor lesions were semiautomatically delineated, with imaging parameters including volume-based and standardized uptake value (SUV)-based metrics. Outcome measures included prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Univariate and multivariate regression analyses assessed the impact of baseline imaging and pretherapeutic clinical parameters on outcome. Event time distributions were estimated with the Kaplan-Meier method, and groups were compared with log-rank tests. Significant prognostic parameters for PSA response and PSA-PFS included log-transformed whole-body SUVmax (odds ratio (OR), 3.26, 95% confidence interval (CI), 2.01-5.55 and hazard ratio (HR), 0.51, 95% CI, 0.4-0.66; both p < 0.001) and prior chemotherapy (OR 0.3, 95% CI, 0.12-0.72 and HR 1.64, 95% CI, 1.07-2.58; p = 0.008 and p = 0.028, respectively). For OS, significant prognosticators were the following log-transformed parameters: number of lesions (HR 1.38, 95% CI, 1.24-1.53; p < 0.001), TTV (HR 1.27, 95% CI, 1.18-1.37; p < 0.001), and ITLV (HR 1.24, 95% CI, 1.16-1.33; p < 0.001), with log-transformed TTV (HR 1.15, 95% CI, 1.04-1.27; p = 0.008) remaining significant in multivariate analysis. At baseline, SUV-based 18F-flotufolastat PET metrics (e.g., whole-body SUVmax) serve as significant positive prognosticators for short-term outcomes (PSA response and PSA-PFS). In contrast, volume-based metrics (e.g., TTV) are significant negative prognosticators for long-term outcome (OS), in mCRPC patients treated with [177Lu]Lu-PSMA-I&T.

Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner. Here, we hypothesized that neuronal hyperactivity and hypersynchronicity, resulting in functional connectivity increases, constitute a crucial mechanism by which Aβ facilitates the spreading of tau pathology. By combining Aβ positron emission tomography (PET), resting-state functional magnetic resonance imaging, and longitudinal tau-PET in 69 cognitively normal amyloid-negative controls and 140 amyloid-positive patients covering the AD spectrum, we confirmed that Aβ induces hyperconnectivity of temporal lobe tau epicenters to posterior brain regions that are vulnerable to tau accumulation in AD. This was replicated in an independent sample of 55 controls and 345 individuals with preclinical AD and low cortical tau-PET uptake, suggesting that the emergence of Aβ-related hyperconnectivity precedes neocortical tau spreading . Last, using longitudinal tau-PET and mediation analysis, we confirmed that these Aβ-related connectivity increases in tau epicenters to typical tau-vulnerable brain regions in AD mediated the effect of Aβ on faster tau accumulation, unveiling increased connectivity as a potential causal link between the two AD hallmark pathologies. Together, these findings suggest that Aβ promotes tau spreading by eliciting neuronal hyperconnectivity and that targeting Aβ-related neuronal hyperconnectivity may attenuate tau spreading in AD.

Amyloid-β deposition in basal frontotemporal cortex is associated with selective disruption of temporal mnemonic discrimination.

Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits. In this context, we tested whether specific domains of mnemonic discrimination, a neural computation essential for episodic memory, exhibit specific deficits related to early Aβ deposition. We tested 108 cognitively unimpaired human older adults (66% female) who underwent 18F-florbetapir positron emission tomography (Aβ-PET), and a control group of 35 young adults, on a suite of mnemonic discrimination tasks taxing object, spatial, and temporal domains. We hypothesized that Aβ pathology would be selectively associated with temporal discrimination performance due to Aβ's propensity to accumulate in the basal frontotemporal cortex, which supports temporal processing. Consistent with this hypothesis, we found a dissociation in which generalized age-related deficits were found for object and spatial mnemonic discrimination, while Aβ-PET levels were selectively associated with deficits in temporal mnemonic discrimination. Further, we found that higher Aβ-PET levels in medial orbitofrontal and inferior temporal cortex, regions supporting temporal processing, were associated with greater temporal mnemonic discrimination deficits, pointing to the selective vulnerability of circuits related to temporal processing early in AD progression. These results suggest that Aβ accumulation within basal frontotemporal regions may disrupt temporal mnemonic discrimination in preclinical AD, and future work is needed to determine whether assessing temporal mnemonic discrimination can aid in predicting emerging AD progression.Significance Statement Identifying subtle cognitive changes that reflect emerging Aβ accumulation could lead to the development of cognitive tasks to detect individuals at risk of AD and sensitively assess clinical intervention outcomes for Aβ-lowering therapeutics. Temporal mnemonic discrimination, the ability to distinguish between events occurring at different times, is supported by basal frontotemporal regions which are among the earliest impacted by Aβ. We demonstrate that Aβ-positivity, as well as increased Aβ deposition in basal frontotemporal regions, is selectively associated with deficits in temporal mnemonic discrimination, but not other domains of mnemonic discrimination such as object identity or spatial relationships. These results suggest that Aβ disrupts cortical circuits supporting temporal processing and highlights inclusion of temporal mnemonic discrimination tasks in future clinical assessments.

Current trends and evidence on post-TEVAR aorto-pulmonary and -bronchial fistula: a narrative review.

Aorto-bronchial or aorto-pulmonary fistulas (ABPF) are a rare but life-threatening complication following thoracic endovascular aortic repair (TEVAR). This narrative review aims to provide an overview of the current trends and available evidence on ABPF following TEVAR, evaluating risk factors, diagnostic approaches, and possible preventive and therapeutic strategies. Relevant publications on post-TEVAR ABPF were selected through a literature search on PubMed. Studies providing data on post-TEVAR ABPF concerning pathogenesis, clinical presentation, diagnostic tools, surgical approaches, and outcomes were included. The literature search obtained 169 articles. After selection, 37 studies, published between 2000 and 2024, remained for analysis. The primary symptom of ABPF is typically hemoptysis, which may be recurrent or persistent. The diagnostic pathway for ABPF encompasses medical history, clinical evaluation, blood tests, sputum and blood cultures. CTA is the first-line imaging modality in suspected ABPF, while bronchoscopy is reserved for hemodynamically stable patients. Moreover, 18-fluoro-deoxyglucose positron emission tomography (PET-CT) can aid in the diagnosis of graft infection. Post-TEVAR ABPF are associated with multiple risk factors, mainly patient-specific clinical conditions (i.e. chronic inflammatory conditions, underlying mediastinal oncologic pathologies, and infectious diseases) and anatomical characteristics, mainly large aortic aneurysms, severe aortic tortuosity, and an extensive peri-aortic hematoma. Strategies to minimize the risk of ABPF formation include appropriate device oversizing, long sealing zones, limited extent of aortic coverage, selective hematoma evacuation, and strict adherence to sterility and antibiotic prophylaxis. Radical surgical interventions have shown superior outcomes compared to endovascular approaches, which may be adopted as initial step to stabilize the patient in a staged treatment. Post-TEVAR ABPF is a rare and life-threatening condition. Literature is scarce and a deeper understanding of risk factors, diagnostic pathways, and therapeutic strategies is essential for the prevention and management of ABPF secondary to TEVAR.