Search Results (1,405)

This work investigated the effect of high CO₂/low O₂ conditions in polyethylene terephthalate (PET) packaging on the quality of fresh-cut broccoli raab, focusing on volatile organic compounds (VOCs). Fresh broccoli raab was stored for 16 days at 5 °C in microperforated (MP) and in non-microperforated (NMP) PET packaging. During storage, the NMP atmosphere reached approximately 17% CO₂ and 0% O₂, while MP packaging maintained approximately 2% CO₂ and 19% O₂. NMP samples became unacceptable by day 7 due to loss of firmness and tissue deterioration, while MP samples remained acceptable until day 10, after which yellowing and shrivelling occurred. By day 10, MP VOCs were characterised by ß-caryophyllene, Z-3-hexen-1-ol acetate, and hexen-1-ol, likely generated by enzymatic reactions associated with tissue senescence. NMP packaging showed a high presence of sulphides, isothiocyanates, and nitriles, indicative of severe tissue damage in anaerobic conditions. These alterations in VOCs led to strong, unpleasant sensory notes in NMP samples. This study demonstrated that MP PET packaging can effectively extend the marketable shelf-life of fresh-cut broccoli raab to 10 days, preserving sensory quality and reducing off-odour formation. The findings highlight the potential of microperforated PET as a sustainable solution for enhancing the shelf-life and quality of perishable produce. Full article

Background: Inflammatory bowel diseases (IBD) rely on invasive methods for detecting intestinal inflammation, with the needs for non-invasive molecular imaging tools being unmet. Integrin α4β7 is a key target in IBD pathogenesis due to its role in the recruitment of T cells. This study aimed to develop a novel ⁶⁸Ga-labeled integrin α4β7-targeted radiopharmaceutical (⁶⁸Ga-A2) and evaluate its feasibility for non-invasive PET/CT imaging of IBD inflammation in a dextran sulfate sodium (DSS)-induced murine colitis model. Methods: ⁶⁸Ga-A2 was synthesized via radiolabeling DOTA-A2 with ⁶⁸Ga. In vitro properties (radiochemical purity, stability, binding specificity, and affinity) of ⁶⁸Ga-A2 were validated. The DSS-induced colitis model was established and confirmed in C57BL/6J mice, followed by in vivo PET/CT imaging, ex vivo biodistribution studies, and histological (HE and IHC) analyses to evaluate the targeting efficacy of ⁶⁸Ga-A2. Results: ⁶⁸Ga-A2 was prepared efficiently (20 min) with a radiochemical purity of >95% and demonstrated good in vitro stability. It exhibited specific binding to integrin α4β7 with a Kd of 68.48 ± 6.55 nM. While whole-body PET/CT showed no visible inflammatory focus uptake, ex vivo imaging and biodistribution of colon tissue revealed significantly higher uptake in DSS-treated mice compared to that in healthy/blocking groups, which was consistent with histological evidence of inflammation. Conclusions: ⁶⁸Ga-A2 demonstrated specific targeting of IBD inflammatory foci in vitro and ex vivo. Despite whole-body imaging limitations, further optimization of its structure may enable it to become a promising non-invasive PET agent for IBD. These findings support future clinical investigations to validate its utility in IBD diagnosis and monitoring. Full article

Inner courtyards have been traditionally used as passive strategy in vernacular buildings in desert climates. This paper presents a study conducted to investigate indoor and outdoor thermal comfort of two vernacular buildings in the hot arid climate of Upper Egypt and proposes an improved solution for courtyards to achieve sustainable development of current vernacular houses and apply the same in the arid climate zone of Egypt. The thermal comfort of vernacular building spaces was evaluated based on using field measurements during the hot season and improvement for courtyards based on ENVI-met V5.6.1 simulation model using three scenarios. Two vernacular buildings (Hassan Fathy and Nubian house) were selected to represent the traditional buildings south of Egypt. The study found that using adobe bricks with high thermal mass in vernacular buildings maintained lower indoor temperature with a range of 2.7 °C to 6.7 °C compared to outdoor temperature; this is considered effective thermal insulation. Meanwhile under extreme hot conditions, courtyard temperature inside the vernacular house was 0.3 K higher than the outdoor. This is not sufficient to maintain indoor thermal comfort without integrating passive solutions inside courtyards. In addition, applying the hybrid solution with big dense trees in the courtyards achieved a significant reduction in PET ranging from 4.2 °C and 5.7 °C; shading the widest area of courtyards and allowing for family activities. The study provided techniques and methodology for the middle courtyard of vernacular buildings, demonstrating how improvement achieves thermal comfort and sustainable development required in the 21st century in Upper Egypt, and can be applied to other vernacular houses in different desert cities in southern Egypt. Full article

Background: The early and accurate identification of Alzheimer’s disease (AD) is complicated by a number of factors, such as the diversity of imaging modalities, variability in scanners across multiple sites, and the long-term progression of neurodegeneration. Such modest gains and the range of diagnostic scenarios suggest that robust multimodal applications, which incorporate both structural, molecular, and longitudinal measurements, are required if realistic benefits are to be seen in actual clinical settings. Methods: We introduce a multimodal self-supervised learning (SSL) approach, which learns feature representations of MRI and PET jointly using the cross-modal alignment, longitudinal temporal consistency, and domain-invariant embedding optimization. The approach integrates contrastive learning, scanner harmonization strategies, and missing modality-aware fusion for handling real-world cohort diversity. Six widely used datasets were evaluated, which are made publicly available: ADNI, OASIS-3, AIBL, BioFINDER, TADPOLE, and MIRIAD. Results: The model performed in a state-of-the-art way on all benchmark tasks. On ADNI, it obtained a BACC of 93.0% and an AUC of 0.96 for the binary classification task (AD vs. CN), surpassing recent baselines such as DiaMond’25, SMoCo, and AnatCL with statistically significant performance gain. Strong cross-cohort generalizability was reported (78.0% BACC on OASIS-3 and 77.5% BACC on AIBL). For TADPOLE, for longitudinal prognosis (i.e., MCI → AD conversion), the model yielded an AUC of 0.85 and a C-index of 0.82, which shows better ascendency over previous SSL-based methods. High test–retest consistency was observed on MIRIAD (ICC = 0.91), indicating that instability in volume measurement due to atrophy progression was minimal. Conclusions: The proposed multimodal SSL framework offers effective transferable and domain-robust biomarkers for the early diagnosis of AD and prediction of MCI-to-AD progression. It has strong cross-dataset generalization. Full article

Background/Objectives: Esophageal cancer (EC) remains highly lethal. The standard management of locally advanced disease includes neoadjuvant chemoradiotherapy (nCRT) followed by surgery. However, the role of esophagectomy in patients achieving clinical complete response (cCR) after nCRT remains uncertain. Methods: We conducted a retrospective study at the Davidoff Cancer Center, Rabin Medical Center (2013–2023). Patients with thoracic EC (adenocarcinoma and squamous cell carcinoma) stage cT2–4a, N+, M0 who received nCRT (cisplatin/5-FU or CROSS regimen with 41.4–50.4 Gy) were included. Patients with cCR, defined by negative biopsies, endoscopic ultrasound, and PET-CT, were managed with surgery or surveillance. Survival was analyzed using Kaplan–Meier and Cox regression. Results: Of 252 patients treated with nCRT, 118 achieved cCR. Seventy underwent surgery, with 47% (33 patients) achieving pathological complete response (pCR), and 48 were managed with surveillance. Five-year overall survival (OS) was 48% with surveillance and 49% with surgery; disease-free survival (DFS) was 36% vs. 43%. No significant differences were observed in OS (HR = 0.75, 95% CI 0.47–1.26) or DFS (HR = 0.88, 95% CI 0.55–1.41). In patients ≤70 years, surgery conferred an OS and DFS benefit (HR = 0.44, p = 0.03). No benefit was observed in patients >70 years, where outcomes trended against surgery. On multivariable analysis, older age (p = 0.005) and female sex (p = 0.007) were independent predictors of OS. Conclusions: In younger patients (≤70 years), surgery yielded significant survival benefit, supporting its role as the preferred treatment. In patients >70 years, surveillance produced comparable or superior outcomes, suggesting deferral of surgery may avoid morbidity without compromising survival. Age-specific tailoring of management is essential. Full article

Poly(ethylene terephthalate) (PET) is a widely used polymer that accumulates in the environment due to its low degradability, requiring efficient recycling strategies. In this study, CaO filler derived from calcium carbide slag (CS) waste was used for the first time as a catalyst for PET depolymerization. PET/CaO composites were prepared via hot extrusion of PET with the finely dispersed CaO filler. The resulting composite demonstrated consistently higher PET conversion (≥95%) and the yields of dimethyl and dibutyl terephthalates (80 and 84%, respectively). Kinetic studies of glycolysis demonstrated that embedding 1 wt% of CaO in the PET matrix doubled the bis(2-hydroxyethyl) terephthalate (BHET) formation rate relative to an externally added CaO catalyst, which resulted in BHET yields of 84.7% and 41.1% after 40 min. SEM and EDX investigations demonstrated good adhesion between the polymer matrix and the filler. The recovered BHET was successfully re-polymerized to produce recycled PET (r-PET). The maximum rate of weight loss of r-PET samples (at T_max = 438.7–444.7 °C) was comparable to the original materials (at T_max = 455.3–457.7 °C). In fact, the direct incorporation of CaO catalyst derived from waste into the polymer matrix during additive manufacturing enabled the implementation of an efficient and scalable closed-loop recycling strategy. Full article

Introduction: Peptide Receptor Radionuclide Therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE is effective in treating advanced Neuroendocrine Tumors (NETs), yet predicting individual response in this treatment remains a challenge due to inter-lesion heterogeneity. There is a lack of standardized, effective methods for using multi-lesion radiomics to predict progression and Time to Progression (TTP) in PRRT-treated patients. This study evaluated how aggregating radiomic features from multiple PET-identified lesions can be used to predict disease progression (event [progression and death] vs. event-free) and TTP. Methods: Eighty-one NETs patients with multiple lesions underwent pre-treatment PET/CT imaging. Lesions were segmented and ranked by minimum Standard Uptake Value (SUV_min) (both descending and ascending), SUV_mean, SUV_max, and volume (descending). From each sorting, the top one, three, and five lesions were selected. For the selected lesions, radiomic features were extracted (using the Pyradiomics library) and lesion aggregation was performed using stacked vs. statistical methods. Eight classification models along with three feature selection methods were used to predict progression, and five survival models and three feature selection methods were used to predict TTP under a nested cross-validation framework. Results: The overall appraisal showed that sorting lesions based on SUV_min (descending) yields better classification performance in progression prediction. This is in addition to the fact that aggregating features extracted from all the lesions, as well as the top five lesions sorted by SUV_mean, lead to the highest overall performance in TTP prediction. The individual appraisal in progression prediction models trained on the single top lesion sorted by SUV_min (descending) showed the highest recall and specificity despite data imbalance. The best-performing model was the Logistic Regression (LR) classifier with Recursive Feature Elimination (RFE) (recall: 0.75, specificity: 0.77). In TTP prediction, the highest concordance index was obtained using a Random Survival Forest (RSF) trained on statistically aggregated features from the top five lesions ranked by SUV_mean, selected via Univariate C-Index (UCI) (C-index = 0.68). Across both tasks, features from the Gray Level Size Zone Matrix (GLSZM) family were consistently among the most predictive, highlighting the importance of spatial heterogeneity in treatment response. Conclusions: This study demonstrates that informed lesion selection and tailored aggregation strategies significantly impact the predictive performance of radiomics-based models for progression and TTP prediction in PRRT-treated NET patients. These approaches can potentially enhance model accuracy and better capture tumor heterogeneity, supporting more personalized and practical PRRT implementation. Full article

Urban densification in post-socialist cities has drastically reduced open and green spaces in high-rise housing areas (HRHAs), intensifying heat stress and degrading outdoor thermal comfort (OTC). These neighborhoods—shaped by socialist-era planning and, later, market-led infill—combine high built density, low greenery, and limited ventilation, making them critical testbeds for climate-adaptive regeneration. This study presents the first empirically validated ENVI-met assessment of blue–green infrastructure (BGI) performance in a post-socialist HRHA, using a representative courtyard in Niš, Serbia, during the 14 August 2024 heatwave. A 24 h field campaign (air temperature, humidity, wind speed, and mean radiant temperature) validated the model with high accuracy (R² = 0.92, RMSE = 1.1 °C for air temperature; R² = 0.88, RMSE = 3.5 K for Physiological Equivalent Temperature (PET). Four retrofit scenarios were simulated: S0 (existing), S1 (grass), S2 (grass + trees), and S3 (S2 + shallow pool). Across all scenarios, daytime PET indicated strong–extreme heat stress, peaking at 61.9 °C (16:00 h). The best configuration (S3) reduced PET by 2.68 °C (10:00 h) but <1 °C at peak hours, with acceptable comfort limited to 04:00–07:00 h. The results confirm that small-scale surface-level greening provides negligible thermal relief under a dense HRHA morphology. Urban morphological reform—optimizing height, spacing, ventilation, and integrated greening—is more effective for heat mitigation. Future work should include multi-seasonal field monitoring and human thermal-perception surveys to link microclimate improvement with exposure and health risk. Full article

Personal protective equipment (PPE) like single-use face masks is discarded after a single use and poses a significant danger to the environment, resulting in plastic pollution. Most of the face masks are made from synthetic polymers and are non-biodegradable to the environment; hence, concerns are being raised about polymers’ environmental impact. Most of the previous studies so far focus on polypropylene (PP) disposable masks and limited data related to environmental abiotic degradation behavior. There is a lack of studies aiming to understand the degradation behavior of different masks and the influence of physical-chemical factors. In this paper, we report on the environmental abiotic degradation of cloth, surgical and respirator filter facepiece 1 (FFP1) masks by accelerated artificial weathering. Furthermore, physical-chemical properties of masks were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Thermo Gravimetric Analysis (TGA). The cloth and FFP1 masks are made from polyethylene terephthalate (PET) and surgical masks were made from polypropylene (PP). Masks were exposed to an accelerated weathering test, which simulates the effects of natural sunlight and reproduces the damage caused by weathering elements such as sunlight, rain and dew. Masks were exposed to Ultraviolet radiation (UV) for 120, 240 and 360 h followed by condensation at 50 °C for 4 h. The FTIR results show that PET cloth and FFP1 PET masks are not degrading with the 360 h maximum exposure duration, which is equivalent to ±180 days. The FTIR scan of the PP surgical mask after 120 h of exposure time shows that it was degraded and broken down into fragments. For the PET cloth mask, a 58% reduction in crystallinity and heat of enthalpy was observed after 120 h of exposure. UV exposure causes a chain scission reaction, breaking down the ester bond in the case of the PET cloth mask. In the case of the PET FFP1 mask exposed to UV for 120, 240 and 360 h, a drastic reduction in crystallinity was observed as compared to the neat (original) PET FFP1 mask. Neat PET cloth and FFP1 masks have higher onset and maximum degradation temperatures as compared to the 120, 240 and 360 h UV exposed masks. Neat PET cloth and FFP1 masks have better resistance to thermal degradation. Full article

We present the cloning and heterologous expression of the α-amylase gene amyBL159 from a thermophilic strain Bacillus licheniformis MGMM159, which was isolated from wastewater sediments self-heated to 70 °C. The gene was successfully cloned into the pET22b and pHT01 vectors, expressed and AmyBL159_Ec and AmyBL159_Bs recombinant α-amylases were purified from Escherichia coli BL21(DE3)pLys and Bacillus subtilis 168 strains, respectively. The AmyBL159_Ec enzyme was most active in the range of 75–95 °C, while AmyBL159_Bs showed maximum activity at temperatures from 45 to 75 °C. AmyBL159_Bs was shown to be more thermostable. Both enzymes were active over a broad pH range of 4.0–12.0. It was shown that Mn²⁺ ions enhanced the activity of both enzymes (up to 163% for AmyBL159_Ec and 142% for AmyBL159_Bs). These results highlight the importance of choosing an expression system for modulating the functional characteristics of recombinant α-amylase. The obtained AmyBL159_Ec and AmyBL159_Bs enzymes are promising for biotechnological applications under extreme conditions. The structure of the α-amylase was generated using the AlphaFold 3 web service. A structure–function analysis of this enzyme and previously studied α-amylases from B. licheniformis identified significant amino acid substitutions at positions 134(133) and 210(209) of the amino acid chain which may contribute to enhanced enzyme thermostability. Full article

The aim of the study was to evaluate the cost-effectiveness of PET/CT in the initial N-staging of head–neck cancer (HNC) and to compare it with alternative strategies using CT or MRI within the Greek National Healthcare System. A cohort of 100 clinically N0 (with no apparent metastatic cervical lymph nodes) HNC patients was simulated over a 10-year time horizon. Initially, a decision tree model was used to simulate the following three different imaging strategies for HNC staging: (a) whole-body FDG-PET/CT, (b) CT of the neck, chest, and abdomen (“CT”), and (c) MRI of the neck plus CT of the chest–abdomen (“MRI”). Subsequently, a Markov model was used to simulate transitions into the health states of recurrence and death. Epidemiological evidence, diagnostic accuracy rates, transition probabilities, and healthcare costs were obtained from the literature and official local tariffs. The estimated total costs per patient were EUR 128,729 for PET/CT, EUR 128,779 for MRI, and EUR 128,585 for CT. The corresponding life years (LYs) were 6.171 LYs for PET/CT, 6.170 LYs for MRI, and 6.170 LYs for CT, respectively. The analysis showed that PET/CT dominates MRI. The incremental cost-effectiveness ratio (ICER) of PET/CT vs. CT was estimated at EUR 144,984 per LY gained. All three imaging strategies had comparable health outcomes and costs, with PET/CT being an appropriate and efficient imaging modality because of its high diagnostic accuracy in the N-staging of HNC. Full article

Background/Objectives: Granzyme B (GZB) PET Imaging is a non-invasive tool that can determine tumoral and systemic effects in immunotherapy. We aim to evaluate ⁶⁸Ga-NOTA-CYT-200 PET Imaging as a molecular imaging approach to determine CAR T-cell therapy response in a human melanoma mouse model. Our goal is to provide a method to monitor CAR T-cell therapy for patients with melanoma and other solid tumors. Methods: A human melanoma mouse model was generated by implanting naïve NSG mice (n = 28) with a human melanoma cell line (A375) subcutaneously (s.c.). After tumor implantation, mice were randomly assigned to receive either the treatment (CAR T) or vehicle solution (controls). After treatment, tumor sizes were measured every other day up to 35 days after cell implantation. ⁶⁸Ga-NOTA-CYT-200 PET Imaging was performed on days 2, 7, and 14 after CAR T-cell administration to assess T-cell activity within the tumors and organs. The PET Imaging results were correlated with IHC and immunofluorescent staining and cytokine assessment of tumor samples. Results: Tracer uptake within tumors of the CAR T group was significantly greater on days 2 (3.1 ± 1.2 vs. 1.1 ± 0.4, p = 0.002) and 7 (2.0 ± 1.1 vs. 1.1 ± 0.1, p = 0.01) after treatment, even before the CAR T group first presented with significantly lower tumor volumes on day 11 after treatment (61.8 mm³ ± 8.7 vs. 287.1 mm³ ± 157.6, p = 0.05). GZB (p = 0.03) and CAR T (p = 0.001) staining were also significantly greater in tumors of CAR T-cell-treated mice. Inflammatory cytokines such as IFN gamma (p = 0.03), CXCL10 (p = 0.004), and CCL5 (p = 0.02) concentrations were also significantly greater in CAR T-cell-treated tumors. Conclusions: CAR-T-treated tumors show significantly elevated ⁶⁸Ga-NOTA-CYT-200 uptake compared with controls, consistent with enhanced effector activity. Full article

We aimed to develop and internally validate a nomogram to estimate axillary pathological complete response (pCR, ypN0) after neoadjuvant systemic therapy (NAST) in clinically node-positive (cN1–2) breast cancer. In a single-center retrospective cohort of 144 consecutive patients treated with NAST (anti-HER2 as indicated), all underwent standardized pre- and post-NAST 18F-FDG PET/CT and axillary staging (sentinel lymph node biopsy [SLNB], targeted axillary dissection [TAD], or axillary lymph node dissection [ALND]). Axillary pCR occurred in 51.4% (74/144). In a multivariable analysis, independent positive determinants of ypN0 included the triple-negative subtype, Modified PERCIST (SUVmax-based) reduction ≥ 80.70%, pre-NAST tumor-to-axilla SUVmax ratio ≥ 1.21, and residual breast tumor size < 0.5 mm; conversely, conglomerate/matted nodal morphology at diagnosis was inversely associated. The model showed good internal discrimination (AUC 0.857, 95% CI 0.797–0.917) and acceptable calibration (Hosmer–Lemeshow p = 0.425). Exploratory, subtype-restricted signals were observed for inflammatory indices within Luminal B (HER2+) but were not retained in the final model. The resulting nomogram—combining tumor biology, PET/CT response, and pre-NAST nodal features—may support risk stratification for axillary de-escalation after NAST; however, prospective external validation—ideally embedded in ongoing de-escalation frameworks—remains essential before clinical implementation, and the tool should currently be regarded as hypothesis-generating rather than a stand-alone decision aid for routine practice. Full article

Background/Objective: Acute and chronic pain affect millions of individuals, yet there are currently no molecular imaging tools to directly assess pain-related mechanisms in the central nervous system (CNS). The voltage-gated sodium channel Na_V1.8 plays a pivotal role in neuropathic pain by increasing the excitability of nociceptive neurons following nerve injury or inflammation. In this work, we aimed to develop a novel positron emission tomography (PET) imaging probe for Na_V1.8 to facilitate noninvasive quantification of this target in the CNS and thereby advance our understanding of pain neurobiology. Methods: We selected the compound suzetrigine, a U.S. FDA-approved, highly selective non-opioid Na_V1.8 inhibitor, as the first candidate for a Na_V1.8-targeted PET tracer. The compound was first assessed using in silico docking and CNS multiparameter optimization (MPO) analysis to evaluate target binding and predicted brain penetrability. Radiolabeling was accomplished by O-methylation with [¹¹C]methyl iodide to yield [¹¹C]suzetrigine without structural modification. The tracer was then evaluated using in vitro binding assays, including autoradiography and saturation binding on rat brain tissues, to determine binding parameters (K_D, B_max), and using in vivo PET imaging in rats to assess brain uptake, time–activity curves (TACs), and tracer behavior under baseline and pretreatment conditions. Pretreatment was performed with unlabeled suzetrigine, the P-glycoprotein (P-gp) inhibitor verapamil, and the heterologous Na_V1.8 inhibitor A-803467. Results: In silico docking demonstrated favorable binding of suzetrigine to the Na_V1.8 active site, and the calculated CNS MPO score (>3.5) suggested adequate brain penetration. Radiochemical synthesis of [¹¹C]suzetrigine via O-methylation yielded a high decay-corrected radiochemical yield (19.2 ± 2.7%, n = 3), excellent purity (>98%, n = 3), and moderate molar activity (62.9 ± 51.8 MBq/nmol, n = 3). Autoradiography on rat brain tissue confirmed saturable and selective binding of [¹¹C]suzetrigine to Na_V1.8. Saturation binding assays revealed a B_max = 93 fmol/mg and a K_D = 0.1 nM, supporting the imageability of Na_V1.8 in the brain using this tracer. In vivo PET imaging in rats demonstrated rapid and sufficient brain uptake but revealed unexpected tracer behavior: signal intensity markedly increased following pretreatment with either unlabeled suzetrigine or the P-gp inhibitor verapamil, and showed a slight increase after pretreatment with the heterologous Na_V1.8 inhibitor A-803467. Detailed analysis of PET images, TACs, and normalized area-under-curve (AUC) values indicated that these atypical uptake patterns were primarily attributable to P-gp-mediated effects, although additional factors may also contribute. Conclusions: [¹¹C]Suzetrigine exhibits high affinity, good brain uptake, and selective target engagement in vitro, supporting its potential as a first-in-class Na_V1.8-PET tracer. However, in vivo performance is confounded by P-gp-mediated efflux and possibly other mechanisms that limit accurate quantification of Na_V1.8 in the living brain. These findings underscore the critical role of efflux transporters in CNS radiotracer development and highlight the need for design strategies that mitigate P-gp interaction when targeting ion channels in the brain. Future studies will include imaging under constant P-gp inhibition, arterial blood sampling for radiometabolite analysis and full kinetic modeling, and evaluation in non-human primates to assess translational feasibility. Full article

Background/Objectives: Leucine-rich repeat kinase 2 (LRRK2) is an enzyme implicated in Parkinson’s disease (PD) and a potential therapeutic target. LRRK2 PET radioligands could therefore function as imaging biomarkers for PD and as tools to measure enzyme occupancy of novel therapeutic candidates. This study aimed at developing novel radioligands for imaging using positron emission tomography (PET). Specific objectives were to synthesize fluorine-18-labeled pyrrolopyridine 1 ([¹⁸F]1), pyrrolo-pyrimidine 2 ([¹⁸F]2), as well as carbon-11-labeled pyrrolo-pyrimidine 3 ([¹¹C]3), and examine their binding specificity, using in vitro autoradiography (ARG) and in vivo positron emission tomography (PET) imaging in non-human primates (NHPs). Methods: Radiolabeling was achieved either by classical one-step fluorine-18 nucleophilic substitution reaction or by methylation using carbon-11 methane. [¹⁸F]1 and [¹⁸F]2 were tested in NHP and human whole-hemisphere ARG experiments. PET imaging was performed in cynomolgus monkeys. Radiometabolites were measured in monkey plasma using gradient HPLC. Results: The results demonstrated successful radiolabeling of all three ligands. In ARG studies, both [¹⁸F]1 and [¹⁸F]2 displayed binding in brain slices from NHP and human samples. The binding of [¹⁸F]1 was blocked by cold Compound 1 and structurally distinct Compound 3, but not by the structurally distinct LRRK2 inhibitor PFE-360. On the other hand, the binding of [¹⁸F]2 was blocked by PFE-360 in certain regions of the brain, indicating some level of specific binding to LRRK2. All three ligands showed relevant brain uptake (>3%ID), with highest uptake being observed for [¹⁸F]1, particularly in the thalamus. In contrast, brain uptake of [¹⁸F]2 and [¹¹C]3 was evenly distributed across all brain regions. No blocking effect of [¹⁸F]1 was observed after pretreatment with the structurally distinct LRRK2 inhibitors PFE-360 (0.5 mg/kg, iv) and GEN-7915 (40 mg/kg). Conclusions: PET imaging indicated a low in vivo specific binding of the radioligands in the cynomolgus monkey brain, suggesting that the radioligands are not suitable for LRRK2 imaging in vivo with PET. This study emphasizes the challenges in the development of PET radioligands for imaging LRRK2 and the need for additional work to achieve this goal. Full article