Search Results (40)

Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: ⁶⁸Ga-FAP inhibitor (FAPI)-04 PET/CT imaging was performed on 61 NSCLC patients to evaluate the clinical significance of FAP. CAFs and normal fibroblasts (NFs) were isolated from patient tissues. Bioinformatic analysis and qRT-PCR were employed to screen and validate miRNAs. Functional assays (CCK-8, collagen contraction, wound healing, transwell co-culture) were utilized to investigate the role of miR-624-5p in regulating fibroblast activation and the effects on the metastatic potential of NSCLC cells. The targeting relationship between miR-624-5p and FAP was validated using FISH, dual-luciferase assay, and Western blotting. Results: ⁶⁸Ga-FAPI-04 uptake was higher in advanced NSCLC (p < 0.001) and correlated with tumor size, lymph node metastases, and distant metastases (p < 0.05). Isolated primary CAFs significantly enhanced the migration and invasion of A549 and PC9 cells compared to NFs (p < 0.001). We identified miR-624-5p as a significantly downregulated miRNA in CAFs (p < 0.001). Functionally, miR-624-5p overexpression inhibited CAF proliferation and collagen contraction (p < 0.01) and reduced the proliferation, migration, and invasion capabilities of A549 and PC9 cells (p < 0.001). Mechanistically, miR-624-5p bound to FAP mRNA and negatively regulated FAP expression (p < 0.001), thus suppressing CAF activation and tumor metastasis. Conclusions: Our findings establish miR-624-5p as a novel upstream regulator that suppresses FAP expression, consequently inhibiting CAF activation and its pro-metastatic function. Targeting the miR-624-5p/FAP axis represents a promising therapeutic strategy for NSCLC metastasis. Full article

Background/Objectives: Hepatocellular carcinoma remains a major cause of death from cancer globally. While ¹⁸F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, ⁶⁸Ga-FAPI PET/CT, which targets fibroblast activation protein in tumor stroma, has emerged as a promising diagnostic tool. In this study, we aimed to assess the diagnostic performance of ⁶⁸Ga-FAPI-04 PET/CT in HCC patients with and without liver cirrhosis and to explore the relationship between PET metrics, tumor size, and PIVKA-II serum marker. Methods: In this prospective single-center study, 59 patients with confirmed HCC (37 with cirrhosis, 22 without) underwent ⁶⁸Ga-FAPI-04 PET/CT. The standard dose (1.5–2.0 MBq/kg) was administered intravenously, and imaging was carried out 60 min post-injection. Semi-quantitative parameters including SUVmax, SUVmean, and tumor-to-background ratio were calculated. Diagnostic performance was assessed using histopathology and multimodal imaging. Statistical analyses included the Mann–Whitney U test and Spearman correlation. Results: The overall sensitivity for HCC detection was 89.8%, with a specificity of 60% and accuracy of 87%. Sensitivity and specificity showed a tendency to be lower in cirrhotic compared with non-cirrhotic patients, with a notably higher background liver uptake in cirrhosis (SUVmax 3.60 vs. 1.3, p < 0.001), resulting in lower TBR values (3.7 vs. 7.0, p < 0.001). A strong correlation between SUVmax and tumor size was seen in non-cirrhotic HCC, while a moderate association between SUVmax and PIVKA-II levels was observed in cirrhotic patients. Conclusions:⁶⁸Ga-FAPI-04 PET/CT demonstrates high sensitivity for HCC detection and may serve as a complementary imaging modality, particularly when interpreted through conventional cross-sectional imaging. Image interpretation in cirrhotic livers may be challenging due to increased background uptake and reduced TBR. Associations between PET-derived parameters, tumor size, and serum PIVKA-II levels should be considered hypothesis-generating and require validation in larger, multicenter studies with clinical outcome data. Full article

Background/Objectives: Fibroblast activation protein (FAP), which is abundantly expressed in cancer-associated fibroblasts (CAFs) across various epithelial malignancies, has emerged as a promising target for molecular imaging and radionuclide therapy. Although several reviews have addressed FAP-targeted diagnostics, a comprehensive synthesis integrating molecular biology, diagnostic performance, and early therapeutic development remains limited. This review summarises the current evidence on radionuclide-labelled FAP inhibitors (FAPIs), with particular emphasis on their diagnostic utility, emerging therapeutic applications, and the structural features that shape their biological behaviour. Methods: A structured literature search was conducted across PubMed, Scopus, and Web of Science, focusing on FAPI-based imaging and therapy. Results: Diagnostic studies consistently demonstrate high tumour-to-background contrast for [⁶⁸Ga]Ga and [¹⁸F]-labelled FAPI radiotracers, particularly in tumours with prominent stromal components such as pancreatic, colorectal, breast, and head and neck cancers. FAPI PET/CT often surpasses [¹⁸F]FDG in lesion conspicuity in the brain, liver, and peritoneum. Therapeutic evidence shows encouraging tumour retention and safety profiles for agents such as [¹⁷⁷Lu]Lu-FAP-2286 and [⁹⁰Y]Y-FAPI-46, while α-emitting radiotracers (e.g., [²²⁵Ac]Ac-FAPI-04) demonstrate potent antitumor effects in preclinical models. Conclusions: Radiolabelled FAPI radiotracers hold significant potential as dual diagnostic and therapeutic agents, particularly for desmoplastic tumours with high CAF content. Nonetheless, clinical evidence remains in its early stages, and substantial questions persist regarding dosimetry, intertumoral variability in FAP expression, and optimal ligand selection for therapy. Continued development of next-generation FAPI constructs, along with well-designed prospective trials, will be crucial in defining the future role of FAPI-based theranostics in oncology. Full article

Background/Objectives: Radiolabeled fibroblast activation protein inhibitors (FAPIs) are emerging as promising imaging agents assessing fibrotic diseases. This study evaluates [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for imaging pulmonary fibrosis in two mouse models, bleomycin-induced (BLM) and a transgenic (fra-2^tg) model, both displaying characteristics of human pulmonary fibrotic diseases. Methods: In the BLM model, C57BL/6 mice were treated with bleomycin or isotonic sodium chloride (controls) for 4, 5, and 6 weeks, followed by [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans. Fra-2^tg mice and wildtype (WT) littermates underwent at 7, 11, and 18/19 weeks of age a PET/CT scan. The selected timepoints correspond to early, middle, and late disease stages for each model. Imaging was complemented by ex vivo quantification, histological, and immunohistochemical (IHC) analyses. Results: In BLM mice, pulmonary [⁶⁸Ga]Ga-DATA^5m.SA.FAPi uptake showed a trend toward increase as early as 5 weeks of treatment compared with the controls, which was confirmed by ex vivo analysis (BLM: 3.31 ± 0.29%ID/g, n = 5; control: 1.61 ± 0.29%ID/g, n = 4; p = 0.0035). In fra-2^tg mice, no significant differences could be detected. IHC revealed elevated pulmonary FAP expression specifically at early (BLM) and mild (fra-2^tg) disease stages, whereas for BLM, tracer uptake was more pronounced at later stages. Conclusions: Our findings complement and extend observations from previous studies and support the potential of FAPI tracers as molecular imaging agents for pulmonary fibrosis. Full article

Background/Objectives: Pulmonary fibrosis is a progressive and fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for the non-invasive assessment of fibrotic activity. This study aimed to evaluate the diagnostic feasibility of [⁶⁸Ga]Ga-FAP inhibitor (FAPI) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) for imaging pulmonary fibrosis in a mouse model. Methods: A pulmonary fibrosis model was established by intratracheal administration of polyhexamethylene guanidine-phosphate (PHMG-p) to C57BL/6 mice. Fibrosis severity was quantified by the Ashcroft scoring system using hematoxylin and eosin and Masson’s trichrome staining and evaluated by computed tomography (CT) imaging at 7, 14, and 21 days after PHMG-p exposure. PET imaging was performed, and ex vivo biodistribution was assessed after injection of [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG. Results: Histological analysis and Ashcroft scoring revealed greater fibrosis severity in the PHMG-p-treated group. Western blot analysis demonstrated upregulation of FAP expression after PHMG-p exposure. CT showed increased mean lung density, while [⁶⁸Ga]Ga-FAPI-04 PET revealed significantly elevated pulmonary uptake of [⁶⁸Ga]Ga-FAPI-04 in the PHMG-p-treated group compared with the controls. [¹⁸F]FDG PET imaging also showed higher uptake of [¹⁸F]FDG in the PHMG-p-treated group than in the controls. Ex vivo biodistribution confirmed greater [⁶⁸Ga]Ga-FAPI-04 accumulation in the lungs of PHMG-p-treated mice. Conclusions: [⁶⁸Ga]Ga-FAPI-04 PET serves as a sensitive imaging biomarker for evaluation of fibrotic activity in PHMG-p-induced pulmonary fibrosis and complements [¹⁸F]FDG PET for assessing disease progression and therapeutic response. Full article

Background: Cardiovascular disease (CVD), driven primarily by atherosclerosis, is a major cause of morbidity and mortality among cancer patients. This study aims to evaluate the diagnostic value of [⁶⁸Ga]Ga-FAPI-PET as a novel molecular imaging tool for atherosclerosis, compared with established, non-specific [¹⁸F]FDG. Methods: We retrospectively analyzed twenty patients with bladder cancer who underwent [⁶⁸Ga]Ga-FAPI positron-emission tomography/magnetic resonance (PET/MR) and [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) at staging. The target-to-background ratio (TBRs) of both tracers were assessed along six arterial segments, and uptake patterns were compared between the two radiotracers. Additionally, associations between the intensity of PET-active lesions and certain CVD risk factors, as well as the intake of acetylsalicylic acid (ASA), were evaluated. Results: [⁶⁸Ga]Ga-FAPI detects significantly more active arterial PET lesions and shows significantly higher uptake than [¹⁸F]FDG in the per-lesion analysis (TBR_FAPI: 1.7 ± 0.5 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p < 0.001) and in the patient-based analysis (TBR_FAPI: 1.7 ± 0.4 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p = 0.018). Arterial hypertension (p < 0.001), dyslipidemia (p < 0.001), and particularly type 2 diabetes mellitus (p < 0.001; difference 34%), were significantly associated with elevated [⁶⁸Ga]Ga-FAPI expression compared to [¹⁸F]FDG uptake. ASA therapy was associated with a significant reduction in arterial [⁶⁸Ga]Ga-FAPI expression than [¹⁸F]FDG (p = 0.02). Conclusions: [⁶⁸Ga]Ga-FAPI-PET imaging, demonstrating superior detection of atherosclerotic activity compared to [¹⁸F]FDG, might be a promising molecular imaging marker for atherosclerosis. Full article

Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy, accounting for less than 1% of all primary hyperparathyroidism (pHPT) cases. It typically presents with pronounced hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. Accurate imaging plays a pivotal role in diagnosis, staging, surgical planning, and long-term surveillance, although differentiating PC from benign disease on imaging remains a significant challenge. A multimodal imaging strategy combining cervical ultrasonography (US) and nuclear medicine techniques provides high sensitivity for lesion detection. Ultrasonography with advanced detective flow imaging allows detailed anatomical assessment and evaluation of vascular patterns of the primary tumor. [^99mTc]Tc-methoxyisobutylisonitrile ([^99mTc]Tc-MIBI) scintigraphy frequently demonstrates prolonged tracer retention in PC, while [¹⁸F]fluorocholine positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging have shown superior performance for detecting both primary tumors and metastatic disease due to its higher spatial resolution and higher molecular sensitivity. [¹⁸F]FDG PET serves as an adjunct modality for identifying aggressive, metabolically active lesions. Emerging radiotracers such as [¹⁸F]-fibroblast activation protein inhibitor ([¹⁸F]FAPI) and [⁶⁸Ga]Ga-trivehexin have shown potential in cases where initial imaging is inconclusive. Theranostic strategies that integrate molecular imaging with targeted radioligand therapy may transform PC management by enabling personalized treatment approaches tailored to each tumor’s biological and imaging characteristics. This review aims to evaluate available imaging modalities for PC diagnosis and provide guidance for their clinical application. Full article

Background/Objectives: Biology-guided radiotherapy (BgRT) is a novel technology utilizing PET radiotracer emissions to deliver image-guided adaptive RT. 18F-Fluorodeoxyglucose ([¹⁸F]FDG) is the most common PET radiotracer but has background in the liver and brain because it is taken up by viable tumor cells as well as inflammatory cells. Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts with minimal expression in normal tissues. FAP inhibitors (FAPIs) bind to FAP, and a FAPI labeled with Gallium-68 (68Ga) is a novel radiotracer with high tumor selectivity. Multiple studies have compared [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for diagnostic imaging, but [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG have never been compared in terms of their utility for BgRT. Purpose: This study was designed to assess the utility of [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for BgRT used to treat pancreatic, liver, lung, head and neck, and cervical cancers. Methods: A radiation oncologist specializing in each cancer contoured the gross tumor volume (GTV) on [¹⁸F]FDG PET-CT and [⁶⁸Ga]Ga-FAPI-04 PET-CT images. Auto-contours were generated using an auto-threshold of 40% of the maximum Standardized Uptake Value (SUV). The suitability of [⁶⁸Ga]Ga-FAPI-04 vs. [¹⁸F]FDG for BgRT was evaluated by comparing Normalized Net Activity Concentration (NNA) and Normalized Target Signal (NTS) for each cancer. Results: NNA and NTS for [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG met the requirements for [¹⁸F]FDG-guided BgRT (NNA > 5.0 kBq/mL, NTS > 2.7) for all disease sites. NNAFAPI was significantly greater than NNAFDG for pancreatic, H&N, and cervical cancer. NTSFAPI was significantly greater than NTSFDG for pancreatic, liver, and lung cancer. Conclusions: [⁶⁸Ga]Ga-FAPI-04 is a novel radiotracer for BgRT and has the greatest potential impact in the treatment of pancreatic cancer. Full article

Primary bone tumors encompass a heterogeneous spectrum ranging from benign entities to highly aggressive sarcomas. This review aims to summarize the current role and future perspectives of nuclear medicine in the diagnosis, staging, and management of primary bone tumors. Accurate diagnosis and staging are critical yet challenging due to histologic heterogeneity and overlapping imaging features. While radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) remain essential, nuclear medicine provides a complementary functional perspective by assessing bone turnover, vascularity, and glucose metabolism. Bone scintigraphy is highly sensitive for skeletal lesions and useful for detecting skip lesions or multifocal disease, although its specificity is limited. Hybrid single-photon emission computed tomography (SPECT)/CT enhances diagnostic confidence through precise anatomic localization and quantitation. [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET)/CT, by directly visualizing tumor metabolism, has become a cornerstone in osteosarcoma and Ewing sarcoma management, demonstrating superiority over bone scintigraphy for detecting skeletal metastases. In chondrosarcoma, [¹⁸F]FDG uptake correlates with histologic grade, although overlap with benign cartilage tumors complicates interpretation. Future directions include the integration of quantitative SPECT, artificial intelligence, and novel tracers such as [¹⁸F]sodium fluoride and [⁶⁸Ga]Ga-fibroblast activation protein inhibitor (FAPI). Collectively, nuclear medicine imaging is becoming a key element in musculoskeletal oncology, offering unique biological insights that complement anatomic imaging and contribute to improved patient management. Full article

Background/Objectives: Bladder cancer is characterized by high recurrence and progression rates, posing a challenge to current diagnostic and treatment strategies. This review aims to provide a comprehensive overview of emerging technologies, including novel PET tracers, AI-assisted cystoscopy, theragnostics, and molecular biomarkers. Methods: We performed a narrative review of the recent literature focusing on innovations in imaging, AI, theragnostics, and biomarker research relevant to bladder cancer diagnosis and management. Results: Several novel PET tracers, such as 68Ga-PSMA and fibroblast activation protein inhibitor (FAPI), demonstrated potential in improving detection sensitivity. AI-enhanced cystoscopy has shown promise in real-time lesion detection, while theragnostic agents enable combined diagnostic and therapeutic applications. Advances in molecular biomarkers, including circulating Tumor DNA (ctDNA) and gene expression signatures, offer new avenues for patient stratification and monitoring. Conclusions: Integration of advanced imaging, AI, theragnostics, and biomarker analysis may transform bladder cancer management, supporting personalized and more effective care strategies. Full article

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [⁶⁸Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients. Full article

Background/Objectives: Over the past four years, ⁶⁸Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) has been established at a tertiary cancer care facility in Jordan. This retrospective study aims to explore tracer uptake metrics across various epithelial neoplasms, identify diagnostic pitfalls associated with ⁶⁸Ga-FAPI PET/CT, and evaluate the influence of ⁶⁸Ga-FAPI PET/CT staging results on changes in therapeutic intent compared to gold standard molecular imaging modalities. Methods: A total of 48 patients with biopsy-confirmed solid tumors underwent 77 ⁶⁸Ga-FAPI PET/CT examinations for molecular imaging assessment, encompassing neoplasms originating from the gastrointestinal tract, head and neck, hepatobiliary system, pancreas, breast, and lung. Results: Notably, pancreaticobiliary tumors exhibited the highest tracer uptake, with mean maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBR) surpassing 10. A comparative sub-analysis of ⁶⁸Ga-FAPI PET metrics in 20 treatment-naïve patients revealed a significant correlation between ⁶⁸Ga-FAPI uptake metrics and tumor grade (Spearman’s rho 0.83; p = 0.00001). Importantly, the results from ⁶⁸Ga-FAPI PET/CT influenced treatment decisions in 35.5% of the cases, primarily resulting in an escalation of management plans. A total of 220 diagnostic challenges were identified across 88.3% of the scans, predominantly within the musculoskeletal system, attributed to degenerative changes (99 observations). Conclusions: This comprehensive analysis highlights the potential significance of ⁶⁸Ga-FAPI PET/CT in oncological imaging and treatment strategy, while also emphasizing the necessity for meticulous interpretation to mitigate diagnostic challenges. Full article

Background: The role of molecular imaging in urothelial cancer is less defined than other cancers, and its utility remains controversial due to limitations such as high urinary tracer excretion, complicating primary tumour assessment in the bladder and upper urinary tract. This review explores the current landscape of PET imaging in the clinical management of urothelial cancer, with a special emphasis on potential future advancements including emerging novel non-¹⁸F FDG PET agents, PET radiopharmaceuticals, and PET-MRI applications. Methods: We conducted a comprehensive literature search in the PubMed database, using keywords such as “PET”, “PET-CT”, “PET-MRI”, “FDG PET”, “Urothelial Cancer”, and “Theranostics”. Studies were screened for relevance, focusing on imaging modalities and advances in PET tracers for urothelial carcinoma. Non-English language, off-topic papers, and case reports were excluded, resulting in 80 articles being selected for discussion. Results: ¹⁸F FDG PET-CT has demonstrated superior sensitivity over conventional imaging, such as contrast-enhanced CT and MRI, for detecting lymph node metastasis and distant disease. Despite these advantages, FDG PET-CT is limited for T-staging of primary urothelial tumours due to high urinary excretion of the tracer. Emerging evidence supports the role of PETC-CT in assessing response to neoadjuvant chemotherapy and in identifying recurrence, with a high diagnostic accuracy reported in several studies. Novel PET tracers, such as ⁶⁸Ga-labelled FAPI, have shown promising results in targeting cancer-associated fibroblasts, providing higher tumour-to-background ratios and detecting lesions missed by traditional imaging. Antibody-based PET tracers, like those targeting Nectin-4, CAIX, and uPAR, are under investigation for their diagnostic and theranostic potential, and initial studies indicate that these agents may offer advantages over conventional imaging and FDG PET. Conclusions: Molecular imaging is a rapidly evolving field in urothelial cancer, offering improved diagnostic and prognostic capabilities. While ¹⁸F FDG PET-CT has shown utility in staging, further prospective research is needed to establish and refine standardised protocols and validate new tracers. Advances in theranostics and precision imaging may revolutionise urothelial cancer management, enhancing the ability to tailor treatments and improve patient outcomes. Full article

Background: Acute liver injury (ALI) is a prevalent and potentially lethal condition globally, where pharmacotherapy plays a vital role. However, challenges such as rapid drug excretion and insufficient concentration at hepatic lesions often impede the treatment’s effectiveness. Methods: We successfully prepared glycyrrhizinate monoammonium cysteine (GMC)-loaded lipid nanoparticles (LNPs) using high-pressure homogenization. The characterization and safety of the LNPs were measured using electrophoretic light scattering (ELS), transmission electron microscopy (TEM), dynamic light scattering (DLS), cytotoxicity assays, and hemolysis tests. The distribution of LNPs in mice was explored using fluorescence labeling methods. The encapsulation efficiency of LNP-GMC was detected using High-Performance Liquid Chromatography (HPLC), and its slow-release effect on GMC was assessed through dialysis. The therapeutic effects of LNP-GMC and pure GMC on the ALI model were evaluated using fibroblast activation protein inhibitor (FAPI) PET imaging, blood biochemical indicators, and liver pathology slices. Results: The encapsulation of GMC in LNPs enhances drug stability and prolongs its hepatic retention, significantly improving its bioavailability and sustained release within the liver. This study also explores the expression of fibroblast activation protein (FAP) in ALI, employing ⁶⁸Ga-FAPI PET/CT imaging for effective differentiation and assessment of liver injury. Conclusions: Our results suggest that LNPs offer an enhanced therapeutic approach for ALI treatment, reducing the required drug dosage, and ⁶⁸Ga-FAPI PET/CT imaging provides a novel method for diagnosis and treatment assessment. This study contributes valuable insights into the utilization of LNPs in liver disease treatment, presenting a promising direction for future clinical applications. Full article