Search Results (230)

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (⁸⁹Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of ⁸⁹Zr-DFO-anti-LAMP1 and ⁸⁹Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with ⁸⁹Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The ⁸⁹Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control ⁸⁹Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUV_max at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUV_max at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas. Full article

This study assesses the clinical deployment of SubtlePET™, a commercial AI-based denoising algorithm, across three radiotracers—¹⁸F-FDG, ⁶⁸Ga-PSMA-11, and ¹⁸F-FDOPA—with the goal of improving image quality while reducing injected activity, technologist radiation exposure, and scan time. A retrospective analysis on a digital PET/CT system showed that SubtlePET™ enabled dose reductions exceeding 33% and time savings of over 25%. AI-enhanced images were rated interpretable in 100% of cases versus 65% for standard low-dose reconstructions. Notably, 85% of AI-enhanced scans received the maximum Likert quality score (5/5), indicating excellent diagnostic confidence and noise suppression, compared to only 50% with conventional reconstruction. The quantitative image quality improved significantly across all tracers, with SNR and CNR gains of 50–70%. Radiotracer dose reductions were particularly substantial in low-BMI patients (up to 41% for FDG), and the technologist exposure decreased for high-exposure roles. The daily patient throughput increased by an average of 4.84 cases. These findings support the robust integration of SubtlePET™ into routine clinical PET practice, offering improved efficiency, safety, and image quality without compromising lesion detectability. Full article

Background: PSMA PET/CT imaging has become a cornerstone in the management of prostate cancer, particularly in the setting of biochemical recurrence (BCR). While semi-quantitative parameters such as SUVmean have been evaluated as prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC), particularly after the VISION trial, the prognostic role of volumetric measures such as Total Molecular Volume (TMV) remain largely unexplored, especially in earlier stages of the disease such as in biochemical recurrence following primary treatment. Methods: This retrospective monocentric study included 84 patients with BCR who underwent PSMA PET/CT imaging between 2020 and 2021 using either [⁶⁸Ga]Ga-PSMA-11(Ga-PSMA) or [¹⁸F]-PSMA-1007 (F-PSMA) as tracers. Total tumor burden was assessed through manual 3D segmentation to derive whole-body Total Molecular Volume (wb TMV) and Total Lesion PSMA (wb TL-PSMA). Clinical and imaging variables were correlated with overall survival (OS) and progression-free survival (PFS) using Cox regression models. Kaplan–Meier analyses were performed based on wb TMV and thresholds determined by the Youden index. Results: A PSMA PET/CT correlation for BCR was identified in 69% of patients, with comparable detection rates between tracers (Ga-PSMA 67% vs. F-PSMA 63%, p = 0.7). A higher wb TMV was significantly associated with worse OS (HR 2.20, p < 0.001) and PFS (HR 2.01, p < 0.001) in univariable analyses. In multivariable models, log₂(wb TMV) remained an independent prognostic factor for PFS (HR 1.78, p = 0.005). Patients with log₂(wb TMV) > 2.87 exhibited significantly poorer survival outcomes. A PSA at diagnosis > 17 ng/mL also predicted shorter PFS. Conclusions: Tumor segmentation from PSMA PET/CT imaging provides powerful prognostic information in patients with biochemical recurrence of prostate cancer, independently of the tracer used. The wb TMV represents a promising volumetric biomarker for future risk stratification and therapeutic decision-making, particularly in earlier stages of prostate cancer progression, where predictive imaging biomarkers remain largely undefined. Full article

Primary hyperparathyroidism is commonly caused by parathyroid adenomas, hyperplasia, or, rarely, carcinoma. In up to 20% of cases, parathyroid tissue may be ectopic, often located in the mediastinum due to aberrant embryologic migration. Ectopic parathyroid glands pose a diagnostic and therapeutic challenge, and an accurate preoperative localization is essential for an effective and safe resection. Imaging modalities such as CT scan, TC-sestamibi scintigraphy, PET/CT, ultrasonography and MRI are routinely employed, whereas combined techniques offer improved diagnostic accuracy. Emerging approaches, however, including PET/CT with choline tracers, have shown promise in enhancing sensitivity in complex or recurrent cases. When ectopic glands are in the mediastinum, thoracic surgical intervention is required. Traditional open approaches, such as sternotomy or thoracotomy, are associated with significant morbidity. The development and evolution of minimally invasive surgery (MIS) has become the preferred approach in selected cases. When MIS is performed, intraoperative assessment and parathyroid identification are crucial to ensure complete gland removal. Intraoperative parathyroid hormone (ioPTH) monitoring provides real-time confirmation of surgical success. The integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques significantly improves surgical outcomes while minimizing complications and accelerating patient recovery. Ultimately, the effective treatment of ectopic parathyroid glands relies on a personalized approach, adapting both diagnostic and surgical strategies to the unique anatomical and clinical context of each patient. Integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques, combined with a multidisciplinary team involving endocrinologists, radiologists, and thoracic surgeons, is key to optimizing outcomes and reducing patient morbidity. Full article

Background/Objectives: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are highly sensitive clinical imaging modalities, frequently employed in conjunction with magnetic resonance imaging (MRI) or computed tomography (CT) for diagnosing a wide range of disorders. Efficient and robust radiolabeling methods are needed to accommodate the increasing demand for PET and SPECT tracer development. Copper-mediated radiohalogenation (CMRH) reactions enable rapid late-stage preparation of radiolabeled arenes, yet synthetic challenges and radiolabeling precursors’ instability can limit the applications of CMRH approaches. Methods: A series of aryl-boronic acids were converted into their corresponding aryl-boronic acid 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] and aryl-boronic acid 1,1,2,2-tetrapropylethylene glycol esters [ArB(Ppin)s] as stable and versatile precursor building blocks for radiolabeling via CMRH. General protocols for the preparation of ¹⁸F-labeled and ¹²³I-labeled arenes utilizing CMRH of these substrates were developed and applied. The radiochemical conversions (RCC) were determined by radio-(U)HPLC. Results: Both ArB(Epin)s and ArB(Ppin)s-based radiolabeling precursors were prepared in a one-step synthesis with chemical yields of 49–99%. Radiolabeling of the aryl-boronic esters with fluorine-18 or iodine-123 via CMRH furnished the corresponding radiolabeled arenes with RCC of 7–99% and 10–99%, respectively. Notably, a radiohalogenated prosthetic group containing a vinyl sulfone motif was obtained with an activity yield (AY) of 18 ± 3%, and applied towards the preparation of two clinically relevant PET tracers. Conclusions: This approach enables the synthesis of stable radiolabeling precursors and thus provides increased versatility in the application of CMRH, thereby supporting the development of novel PET and SPECT radiotracers. Full article

Background/Objectives: Pulmonary lymphangitic carcinomatosis (PLC) is a rare, aggressive manifestation of metastatic cancer characterized by lymphatic infiltration of the lungs, typically indicating advanced disease and poor prognosis. Methods: This comprehensive narrative review evaluates the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging in assessing PLC. Results: Current evidence demonstrates that [18F]FDG PET/CT achieves high diagnostic accuracy, with sensitivity and specificity ranging from 86 to 97% and 84 to 100%, respectively, particularly when employing semiquantitative metrics such as peritumoral standardized uptake value (SUVmax) thresholds (e.g., ≥2.1). PET/CT surpasses high-resolution computed tomography (HRCT) in distinguishing PLC from mimics like pulmonary sarcoidosis by identifying distinct metabolic patterns: bronchovascular hypermetabolism in PLC versus subpleural nodular uptake in sarcoidosis. Prognostically, metabolic tumor burden (e.g., SUVmax × involved lobes) and novel cPLC classifications (localized to the ipsilateral or contralateral lung) independently predict progression-free survival. However, challenges persist, including non-specific tracer uptake in inflammatory conditions and variability in SUV measurements due to technical factors. Emerging digital PET/CT systems, with enhanced spatial resolution, may improve the detection of focal PLC and reduce false negatives. While [18F]FDG PET/CT is invaluable for whole-body staging, therapeutic monitoring and biopsy guidance, the standardization of protocols and multicenter validation of prognostic models are critical for clinical integration. Future research should explore novel tracers (e.g., PSMA for prostate cancer-related PLC) and machine learning approaches to refine diagnostic and prognostic accuracy. Conclusions: This review underscores the role and the transformative potential of [18F]FDG PET/CT in PLC management while advocating for rigorous standardization to maximize its clinical utility. Full article

Background: ¹⁸F-NaF and ^99mTc-MDP are widely used bone imaging tracers, but their comparative uptake in bone versus cartilage is unclear. This study aimed to directly compare these patterns in rats to guide musculoskeletal molecular imaging. Methods: Male Sprague-Dawley rats underwent in vivo and ex vivo radiotracer studies. Tracer uptake (%ID/g) was quantified in bone and cartilage at 30, 60, or 120 min post-injection (¹⁸F-NaF or ^99mTc-MDP), and across different ages. Additional rats received subcutaneous implants of viable or devitalized bone and cartilage; uptake was assessed using PET/CT, autoradiography, and histology. Results: ¹⁸F-NaF showed faster blood/background clearance and higher target-to-background ratios compared to ^99mTc-MDP, especially in weight-bearing joint cartilage. ¹⁸F-NaF uptake in cancellous bone significantly exceeded that of ^99mTc-MDP, whereas ^99mTc-MDP showed higher uptake in knee cartilage. Age-related analysis showed maximal knee cartilage accumulation in aged rats. Histological and cell inactivation studies confirmed that ¹⁸F-NaF uptake reflects both cellular activity and degree of calcification. Conclusions:¹⁸F-NaF demonstrates distinctive, quantifiable uptake in cartilage, dependent on both cellular activity and calcification, and exhibits favorable imaging characteristics versus ^99mTc-MDP for cartilage metabolism. These findings support ¹⁸F-NaF as a promising tool for early diagnosis and therapeutic monitoring of bone and joint disorders, and provide pathophysiological insight into the dynamics of the bone–cartilage interface. Full article

Neuroendocrine neoplasms (NENs) represent a heterogenous group of tumors with significant inter- and intra-patient variability. Once considered to be rare, neuroendocrine neoplasms are being increasingly recognized through the advent of advanced diagnostic techniques, which may be contributing to the significant increase in the incidence and detection rate of these tumors. NENs can be classified into well differentiated and poorly differentiated neuroendocrine tumors (NETs) or neuroendocrine carcinomas (NECs). The proliferation rate of NETs can vary from Ki-67 1–55%. In addition, the SSTR expression can vary significantly. Because of this high “heterogeneity”, their detection and characterization have become essential to disease management, leading to dual-tracer imaging, most commonly with FDG- and SSTR-targeted PET/CT. Because of the complexity of the disease, the optimal treatment of patients depends on a combination of imaging, serological biomarkers, and clinical information. There remains a significant portion of patients who do not respond as anticipated, and the management of their disease remains challenging with current techniques, necessitating the refinement of our technologies and the development of new ones. In addition to new biological targets, improved peptide vector targeting for the somatostatin receptor needs further development. This review aims to evaluate the existing imaging techniques utilized in the diagnosis, assessment, and treatment of NENs, as well as the emerging radiopharmaceuticals and technologies, which will expand our imaging repertoire as well as our management options. Full article

Background/Objectives: This study evaluates and compares the diagnostic accuracy of [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 for lymph node staging in patients with prostate cancer (PCa) scheduled for robot-assisted radical prostatectomy (RARP) and lymphadenectomy (LND). Methods: We retrospectively reviewed prospectively collected data on patients referred to our hospital from October 2020 to January 2023. We included all patients who underwent [68Ga]Ga-PSMA-11 or [18F]F-PSMA-1007 PET/CT for primary staging and subsequently had RARP with concomitant LND. The maximum standard uptake value (SUVmax) for lymph nodes (LNs) and the SUV node-to-background ratio were reported. Two different cut-off values for the SUV node-to-background ratio (i.e., ≥2 vs. <2 and ≥15.5 vs. <15.5) were used to evaluate the diagnostic performance of both tracers. The first cut-off was empirically chosen, while the second was based on Liu’s method. Results: A total of 156 patients were included (median age: 67 years). Among them, 83 underwent [68Ga]Ga-PSMA-11 and 73 underwent [18F]F-PSMA-1007 PET/CT. Suspicious lymph nodes were identified in 21 patients (13.5%). Pathological nodal involvement (pN1) was confirmed in 25 cases (16%). Of the 21 patients with suspicious pathological lymph nodes on PSMA PET/CT, 9 (42.9%) had positive nodes on the final pathology report. With an SUV node-to-background ratio cut-off of ≥2, [68Ga]Ga-PSMA-11 showed 37.5% sensitivity (SE) and 98.5% specificity(SP), while [18F]F-PSMA-1007 demonstrated 33.3% SE and 100% SP. Using the ≥15.5 cut-off, SE and SP were 31.3% and 100% for [68Ga]Ga-PSMA-11 and 11.1% and 100% for [18F]F-PSMA-1007, respectively. Conclusions: [18F]F-PSMA-1007 PET/CT showed, even if not statistically significantly, slightly lower SE and higher SP for nodal staging compared to [68Ga]Ga-PSMA-11 PET/CT, irrespective of the SUV ratio used. Full article

Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[¹⁸F]fluoro-D-glucose [¹⁸F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [⁶⁸Ga]Ga-Trivehexin PET probe. Methods: The literature review on [⁶⁸Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field. Results: This study highlights the significant advancements achieved with [⁶⁸Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer’s pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [¹⁸F]FDG. Furthermore, [⁶⁸Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability. Conclusions: [⁶⁸Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP). Full article

Objectives: Tumor heterogeneity and acquired resistance to prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT) pose significant challenges to PSMA PET-based diagnosis. This study aimed to develop an Al¹⁸F-labeled FAP-targeted tracer and explore the diagnostic value in acquired drug-resistant tumor models. Methods: To identify potential targets for imaging drug-resistant prostate cancer, bioinformatic analysis was employed to correlate FAP expression levels with genes associated with tumor progression and radiotherapy resistance. Molecular docking technology simulations were utilized to screen FAP ligands for optimal binding affinity and target specificity. The most promising ligand, FAP-2286, was radiolabeled with ¹⁸F to develop a novel PET imaging agent, Al¹⁸F-NOTA-FAP-2286 PET. To evaluate the diagnostic potential of this agent, various tumor models were established. U87 cells were used to optimize the imaging protocol and assess targeting efficiency and 22RV-1-resistant cells co-xenografted with NIH-3T3 cells were used to model acquired drug-resistant prostate cancer. The diagnostic efficacy of Al¹⁸F-NOTA-FAP-2286 PET in this acquired drug-resistant model was assessed and validated through immunohistochemical staining of tumor tissue. Results: Bioinformatic analysis confirmed the association between FAP expression and key genes involved in radiotherapy resistance, such as HIF1α, BCL2, ATM, and EGFR. Molecular docking studies demonstrated the strong binding affinity of FAP-2286 to FAPα (−10 kcal/mol). Al¹⁸F-NOTA-FAP-2286 PET/CT imaging in U87 tumor-bearing mice revealed accurate targeting of high FAP-expressing xenografts. The imaging characteristics of Al¹⁸F-NOTA-FAP-2286 were comparable to ¹⁸F-FDG and ⁶⁸Ga-FAP-2286 but with a prolonged imaging window compared to ⁶⁸Ga-FAP-2286. In acquired drug-resistant prostate cancer xenograft nude mice, Al¹⁸F-NOTA-FAP-2286 could effectively detect tumor lesions, as confirmed by immunohistochemical analysis. Conclusions: Al¹⁸F-NOTA-FAP-2286, as a PSMA-independent imaging agent, holds promise as a valuable complementary molecular imaging tool for assessing acquired resistance to PRLT. Full article

Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node biopsy (SNB) represents an imaging-guided technique that could enhance nodal staging accuracy by leveraging lymphatic mapping with tracers. PSMA-RGS uses radiolabeled tracers with the aim to improve intraoperative lymph node metastases (LNMs) detection. Several studies demonstrated its feasibility and safety, with promising accuracy in nodal staging during robot-assisted radical prostatectomy (RARP) and in recurrence setting during salvage lymph node dissection (sLND) in patients who experience biochemical recurrence (BCR) after primary treatment and have positive PSMA positron emission tomography (PET). Near-infrared PSMA tracers, such as OTL78 and IS-002, have shown potential in intraoperative fluorescence-guided surgery, improving positive surgical margins (PSMs) and LNMs identification. Finally, augmented reality (AR), which integrates preoperative imaging (e.g., multiparametric magnetic resonance imaging [mpMRI] of the prostate and computed tomography [CT]) onto the surgical field, can provide a real-time visualization of anatomical structures through the creation of three-dimensional (3D) models. These technologies may assist surgeons during intraoperative procedures, thus optimizing the balance between oncological control and functional outcomes. However, challenges remain in standardizing these tools and assessing their impact on long-term PCa control. Overall, these advancements represent a paradigm shift toward personalized and precise surgical approaches, emphasizing the integration of innovative strategies to improve outcomes of PCa patients. Full article

Metastases to the breast from non-mammary malignancies are rare, accounting for 0.1–5% of all breast malignancies. Neuroendocrine tumors (NETs) rarely metastasize to the breast. PET-CT somatostatin receptor imaging plays a pivotal role in the staging and follow-up of NETs, leveraging tracers like 68Ga-DOTATOC that bind to somatostatin receptors (SSTRs) expressed on tumor cells. While both primary and metastatic NETs express SSTRs, primary breast tumors may also exhibit an uptake of 68Ga-somatostatin analogs, making the differential diagnosis between primary breast tumors and neuroendocrine metastases challenging. Additionally, imaging characteristics of breast metastases from NETs are poorly documented in the literature, posing a diagnostic challenge that extends to pathology, particularly when in the absence of clinical suspicion. Misdiagnosis in such cases can lead to inappropriate therapeutic interventions. We report the case of a 75-year-old female patient with a history of pancreatic NET who presented to our breast clinic for further evaluation of a breast mass after a PET-CT scan revealed moderate 68Ga-DOTATOC uptake. Multimodality breast examination, including mammography and multiparametric US with B-mode, Color Doppler, Strain Elastography (SE), Shear Wave Elastography (SWE), and contrast-enhanced US (CEUS), was performed. Following a core biopsy, the lesion underwent surgical excision, revealing the diagnosis of NET metastasis. This case highlights a rare instance of neuroendocrine tumor metastasis to the breast, assessed using various ultrasound techniques, with detailed imaging and quantitative analysis. The comprehensive multimodal assessment contributes to the limited body of literature and provides elements for the differential diagnosis of a rare breast lesion that should always be considered in the presence of a known primary NET. Full article

Background: Hypoxia plays a critical role in lung cancer progression and treatment resistance by contributing to aggressive tumor behavior and poor therapeutic response. Molecular imaging, particularly positron emission tomography (PET), has become an essential tool for noninvasive hypoxia detection, providing valuable insights into tumor biology and aiding in personalized treatment strategies. Objective: This narrative review explores recent advancements in PET imaging for detecting hypoxia in lung cancer, with a focus on the development, characteristics, and clinical applications of various radiotracers. Findings: Numerous PET-based hypoxia radiotracers have been investigated, each with distinct pharmacokinetics and imaging capabilities. Established tracers such as ¹⁸F-Fluoromisonidazole (¹⁸F-FMISO) remain widely used, while newer alternatives like ¹⁸F-Fluoroazomycin Arabinoside (¹⁸F-FAZA) and ¹⁸F-Flortanidazole (¹⁸F-HX4) demonstrate improved clearance and image contrast. Additionally, ⁶⁴Cu-ATSM has gained attention for its rapid tumor uptake and hypoxia selectivity. The integration of PET with hybrid imaging modalities, such as PET/CT and PET/MRI, enhances the spatial resolution and functional interpretation, making hypoxia imaging a promising approach for guiding radiotherapy, chemotherapy, and targeted therapies. Conclusions: PET imaging of hypoxia offers significant potential in lung cancer diagnosis, treatment planning, and therapeutic response assessment. However, challenges remain, including tracer specificity, quantification variability, and standardization of imaging protocols. Future research should focus on developing next-generation radiotracers with enhanced specificity, optimizing imaging methodologies, and leveraging multimodal approaches to improve clinical utility and patient outcomes. Full article