Molecular Imaging and Biology最新文献

Purpose: Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a 5-year survival rate below 10% and poor prognosis. Early diagnosis of PDAC remains a significant challenge due to its nonspecific symptomatology, insufficient reliable biomarkers, aggressive tumor progression with early metastatic spread, and limited effective screening protocols. Recent research indicates cannabinoid type 2 receptor (CB2R) overexpression in PDAC, leading to the development of [¹⁸F]JR-1004 as a potential CB2R-targeted PET probe to address diagnostic challenges in this aggressive malignancy.

Procedures: The probe development utilized computer-aided drug design, incorporating modifications to a triaryl sulfonamide CB2R inverse agonist lead compound. Essential pharmacophoric elements (central sulfonamide, flanking aromatic rings) were preserved, while the para-methoxy group underwent conversion to a tosylate precursor for radiolabeling. Radiolabeling with ¹⁸F was performed using a JiRui OnePlatform 3.1 s synthesizer (synthesis time: 70 min).

Results: The radiochemical purity and yield achieved values exceeding 95% and 16.7%, respectively. In vitro studies confirmed [¹⁸F]JR-1004's specific binding affinity in CB2R-overexpressing cells, with uptake significantly reduced by a CB2R antagonist administration. PET imaging in PDAC mouse models revealed significant accumulation in tumor regions, with receptor specificity validated through CB2R blocking studies. Biodistribution analysis revealed primary probe metabolism through the hepatobiliary system, with maximal uptake in the liver and pancreas. The probe's targeting profile demonstrates notable improvements for PDAC detection compared to the relatively nonspecific uptake patterns of [¹⁸F]FDG PET in pancreatic imaging.

Conclusions: This investigation presents an innovative molecular imaging approach for early PDAC diagnosis, exhibiting considerable potential for clinical implementation.

Purpose: Accurate staging of prostate cancer is essential for therapeutic decision-making. While PSMA PET-CT reports offer rich clinical data, their unstructured format hinders large-scale analysis. Recent advances in large language models (LLMs) offer new opportunities to extract structured information from narrative radiology reports. However, their ability to perform multi-step clinical reasoning, particularly for cancer staging, remains underexplored.

Methods: In this feasibility study, 80 anonymized, Turkish-language PSMA PET-CT reports were independently interpreted by two LLMs-Gemini 2.5 Pro (Google) and ChatGPT 4o (OpenAI). Using a structured prompt containing an embedded knowledge base (AJCC/CHAARTED criteria) and few-shot examples, both LLMs generated classifications for T, N, M, and overall clinical stage/disease volume. Outputs were benchmarked against expert classifications by a senior nuclear medicine specialist. Performance was evaluated using accuracy, precision, recall, F1-score, and Cohen's kappa.

Results: For the composite task of classifying clinical stage and disease volume, Gemini 2.5 Pro achieved an accuracy of 93.8% (95% CI: 86.0-97.9) and a Cohen's kappa of 0.910 (95% CI: 0.834-0.986), while ChatGPT 4o achieved 91.3% accuracy (95% CI: 82.8-96.4) with a kappa of 0.874 (95% CI: 0.786-0.962). For T staging, Gemini showed a higher accuracy point estimate (95.0% [95% CI: 87.7-98.6] vs. 91.3% [95% CI: 82.8-96.4]), while both models excelled at the binary N and M classifications, achieving accuracies above 95% and kappa values indicating near-perfect agreement (κ > 0.900).

Conclusions: LLMs, when guided by expert-informed prompt engineering, can accurately stage prostate cancer from free-text PSMA PET-CT reports and may serve as a powerful assistive tool for data automation, research acceleration, and quality assurance.

Purpose: We aimed to compare the diagnostic performance of [⁶⁸Ga]Ga-FAPI-04 PET/CT, [¹⁸F]F-FDG PET/CT, enterography and intestinal ultrasound (IUS) in detecting inflamed segments in patients with Crohn's disease (CD), as well as in identifying CD-related complications.

Methods: This prospective study enrolled 16 patients with CD. Each patient underwent [⁶⁸Ga]Ga-FAPI-04 PET/CT, [¹⁸F]F-FDG PET/CT, enterography, and IUS within 14 days. Using endoscopic results as the reference standard, we assessed the diagnostic accuracy and agreement across these imaging modalities for detecting segmental lesions in the proximal upper gastrointestinal (GI) tract and ileocolon. Their performance in identifying CD-associated complications and mesenteric changes was also evaluated.

Results: [⁶⁸Ga]Ga-FAPI-04 PET/CT exhibited high sensitivity (73.3%, 95% CI: 0.610-0.829), specificity (97.8%, 95% CI: 0.887-0.996) and accuracy (84.0%, 95% CI: 0.758-0.897) for detecting segmental lesions in the terminal ileum and colon. These performance metrics were comparable to those of enterography, [¹⁸F]F-FDG PET/CT and IUS (all P > 0.05), with nearly perfect diagnostic agreement observed among these imaging modalities (all κ > 0.81; all P < 0.001). In the upper GI tract and proximal small intestine, its sensitivity (53.8%, 95% CI:0.291-0.768), specificity (92.1%, 95% CI:0.792-0.973) and accuracy (82.4%, 95% CI:0.697-0.904) were similar to [¹⁸F]F-FDG PET/CT and enterography, with good diagnostic agreement (both κ = 0.73; P < 0.001). However, its resolution was suboptimal for detecting mild lesions. Notably, [⁶⁸Ga]Ga-FAPI-04 PET/CT outperformed other imaging methods in detection rate and sensitivity for identifying CD-associated complications and mesenteric changes.

Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/CT may sever as a one-step, non-invasive diagnostic option for CD patients.

Purpose: Early detection and intervention in lung adenocarcinoma (LUAD) are critical for improving patient prognosis. This study explores the role of basic leucine zipper and W2 domains 1 (BZW1, BZAP45) in regulating malignant cellular behavior and glycolytic metabolism in LUAD.

Procedures: Bioinformatics and clinical information analysis was conducted to study BZW1 expression and its relationship with prognosis, glycolysis-related genes expression and PET/CT parameters of 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) in LUAD. BZW1 was knocked out in A549 cell line and verified. In vitro and in vivo studies were performed to analyze BZW1's impact on malignant behaviors and glycolysis. Non-targeted mass spectrometry analyzed xenograft tumor metabolites and potential biomarkers.

Results: Bioinformatic analyses identified BZW1 as a pivotal gene driving LUAD progression. The retrospective analysis revealed that BZW1 expression is elevated in LUAD tissues and is significantly correlated with clinical tumor parameters and metabolic parameters obtained from [¹⁸F]FDG PET/CT. In vitro assays demonstrated that BZW1 overexpression promotes LUAD cell proliferation, migration, and invasion. In vivo experiments with mouse xenograft models confirmed that BZW1 promotes tumor growth. Further analysis revealed that BZW1 may facilitate glycolysis and the Warburg effect by upregulating hypoxia inducible factor-1α (HIF-1α) and cellular Myelocytomatosis (c-Myc).

Conclusions: These findings highlighted the role of BZW1 in LUAD metabolism and may promote tumor progression through modulating of glycolytic pathways. In conclusion, BZW1 is significantly associated with LUAD malignancy and [¹⁸F]FDG PET/CT derived metabolic parameters. It could provide a potential molecular target for the diagnosis and treatment of LUAD, offering new insights into precision oncology.

Background/objectives: Immune checkpoint blockade (ICB) therapy has been ineffective in glioblastoma (GBM) that recurs following standard-of-care resection and chemoradiation of the primary tumor. Herein, we investigate whether the delayed effect of intracranial radiation alters the tumor lesion metabolic profile.

Methods: Naïve (non-irradiated) GL261 tumor cells were implanted into the brains of C57BL/6 mice. Brains of one cohort were hemispherically irradiated six weeks prior to implantation, ultimately resulting in ICB refractory GBM. Brains of the control cohort were not irradiated. Following subcutaneous infusion of [6,6-²H₂] glucose (Glc), single voxel deuterium metabolic imaging (DMI) monitored Glc uptake and the production of semi-heavy water (HOD), ²H₂-lactate (Lac) and the 50/50 mix of [²H₂-glutamate + ²H₂-glutamine] (Glx).

Results: GL261 tumors growing in previously irradiated brain showed reduced Warburg effect (aerobic glycolysis; glucose → lactate) and greater TCA cycle activity (respiration, oxidative phosphorylation) relative to tumors growing in non-irradiated brain as evidenced by cohort differences in the ratios Glx/Lac (p < 0.01), Glx/Glc (p < 0.02), and Lac/Glc (p < 0.01).

Conclusions: A metabolic program skewed toward oxidative phosphorylation and away from glycolysis has been associated with immune dysfunction. This study documents such a skewed metabolic state in ICB refractory GL261 GBM growing in irradiated brain (tumors were not irradiated) compared to control brain.

Objective: To investigate the feasibility of early dynamic 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging in predicting epidermal growth factor receptor (EGFR) and tumor protein 53 (TP53) mutation status in lung adenocarcinoma (AC).

Methods: In total, 81 patients with lung nodules underwent early dynamic PET (10 min after injection) and late static PET (60 min after injection), and 41 (18 male, 23 female; mean age 64 ± 10 years) with confirmed AC were included in the final analysis. Dynamic images were reconstructed into 25 frames, and time-to-activity curves were generated. An irreversible two-tissue compartment model was used to derive kinetic parameters (K_1, k₂, k₃, Ki, and MR_FDG). EGFR and TP53 mutation statuses were determined via histological analysis. Statistical tests, including the Wilcoxon rank-sum test, Kruskal-Wallis H test, and Spearman's correlation, were used to assess differences and associations among groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance.

Results: In patients with AC, k₃, Ki, and MR_FDG were strongly correlated with SUV_max (r = 0.821, 0.862, and 0.778, respectively; all P < 0.001). SUV_max, k₃, Ki, and MR_FDG differed significantly between patients with AC and SCC, as well as across TNM and pathological stage subgroups (P < 0.05). SUV_max and k₃ were significantly lower in the EGFR-positive group, while Ki was higher in the TP53-positive group (P < 0.05). AUCs for predicting EGFR mutation were 0.718 (SUV_max) and 0.776 (k₃), and 0.703 (Ki) for TP53 mutation.

Conclusions: Early dynamic ¹⁸F-FDG PET/CT may serve as a valuable non-invasive tool for predicting EGFR and TP53 mutation status in AC, for screening patients for targeted therapy.

Atherosclerosis (AS) is a chronic condition defined by the accumulation of plaque fundamentally resulting from the deposition of low-density lipoprotein and fibrous compounds within injured arteries. Current treatments for atherosclerosis are effective, but the complex and not fully understood underlying mechanisms limit their effectiveness. Moreover, early detection of AS continues to be a real challenge. Innovative therapeutic approaches, such as the application of nanomedicines and theragnostic, are increasingly attracting the interest of researchers globally. Gold nanoparticles (AuNPs) exhibit significant potential as theragnostic agents in the context of atherosclerosis, providing both diagnostic and therapeutic functionalities. This review will discuss current strategies utilizing AuNPs and explore potential future advancements involving theragnostic AuNPs that may aid in addressing AS.

Purpose: This study aimed to assess the feasibility of intraoperative fluorescence imaging using the PSMA-targeted fluorescent tracer OTL78 for detecting lymph node metastases during pelvic lymph node dissection (PLND) in patients undergoing staging or salvage surgery for prostate cancer.

Procedures: In a prospective pilot study, six patients scheduled for robot-assisted PLND received a single intravenous infusion of OTL78 at a dose of either 0.06 mg/kg or 0.03 mg/kg, administered 1-2 h prior to surgery. Intraoperatively, lymph node clusters were evaluated using fluorescence imaging. Post-surgical histopathological analysis and immunohistochemistry were performed to confirm tumor presence and PSMA overexpression in fluorescent nodes. The primary outcome was the feasibility of fluorescence imaging in detecting metastatic lymph nodes during PLND.

Results: Fluorescence imaging demonstrated a sensitivity of 66.7% and specificity of 91.7% for identifying metastatic lymph nodes. The positive predictive value was 66.7%, and the negative predictive value was 91.7%. Metastasized lymph nodes (MLN) exhibited significantly higher median fluorescence intensity (MFI) than benign lymph nodes (BLN): 0.51 [IQR 0.11-0.74] vs. 0.06 [IQR 0.03-0.12], p = 0.024. Immunohistochemistry confirmed PSMA overexpression in fluorescent malignant regions. No adverse reactions to the tracer were reported.

Conclusions: Intraoperative fluorescence imaging with the tracer OTL78 is a feasible technique for identifying metastatic lymph nodes during PLND. Fluorescence guidance may assist in detecting small metastatic deposits within nodal clusters that are otherwise difficult to localize. Larger studies are needed to validate these findings and optimize the imaging protocol for broader clinical use.

Purpose: Immune checkpoint inhibition has shown promising results in malignant melanoma, but not all patients respond equally well, necessitating early, accurate monitoring of immunotherapy response. [¹⁸F]FDG-PET/CT aids in characterising therapy response beyond morphology, but validated imaging biomarkers for immunotherapy response remain scarce. This study investigated three-time point [¹⁸F]FDG-PET/CT to monitor combined anti-PD-L1/anti-CTLA-4 immunotherapy in murine melanoma allografts and compared quantitative in vivo imaging biomarkers with ex vivo biomarkers from multiparametric immunohistochemistry at each time point.

Procedures: Melanoma cells (B16-F10) were injected subcutaneously into C57BL/6 mice (n = 40). Seven days post-inoculation, baseline [¹⁸F]FDG-PET/CT was conducted. Animals were randomized into two groups; the therapy group received 5 i.p.-injections of anti-PD-L1/anti-CTLA-4 (20 µg/kg) on days 7, 9, 11, 13 and 15 after tumor cell inoculation. The control group received sham treatment. PET/CT was performed at baseline (day 7 post inoculation), follow-up 1(day 13; FU-1) and follow-up 2 (day 19; FU-2). Tumor allografts were harvested at each time point for immunohistochemistry (CD8, Ki-67, TUNEL) to validate imaging parameters (MTV, SUVmax).

Results: At FU-1, the therapy group exhibited significantly lower MTV than the control group (p = 0.004). At FU-2, MTV and SUVmax were significantly lower (MTV: p = 0.008; SUVmax: p = 0.0003) compared to controls. Ex vivo analysis revealed significant anti-tumor effects in the therapy group, with higher apoptosis rates (FU-1: p = 0.012; FU-2: p = 0.001), more CD8-positive T-cells (FU-2: p = 0.003) and lower tumor cell proliferation (FU-1: p = 0.012; FU-2: p = 0.012).

Conclusions: Multi-time point [¹⁸F]FDG-PET/CT allowed for early non-invasive monitoring of combined anti-PD-L1/anti-CTLA-4 immunotherapy in experimental melanomas, validated by multiparametric immunohistochemistry with significant pro-immunogenic, pro-apoptotic and anti-proliferative effects.

Purpose: Peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE is an established treatment option for neuroendocrine tumors (NETs) and has been extended to other somatostatin receptor (SSTR)-expressing tumors. We aimed to determine its efficacy and safety profile in patients with advanced radioiodine-refractory differentiated thyroid carcinoma (DTC).

Methods: Seven radioiodine-refractory DTC patients undergoing at least two cycles of PRRT were included. Patients were subdivided into continuous treatment (defined as sequential application of PRRT; 5/7 (71.4%)) vs. discontinuous treatment (with at least one-year PRRT-free interval; 2/7 (28.6%)). Baseline SSTR PET was analyzed to determine patients' eligibility for PRRT. Response was assessed by tumor control as defined by stable (± 30.0%) or decreasing (≥ 30.0%) total tumor volume (PET-derived TTV), thyroglobulin (Tg) and RECIST 1.1 criteria.

Results: SSTR PET showed discernible high uptake (maximum standardized uptake values, 10.4 ± 8.6) in metastases, in particular in the skeleton. Continuous PRRT showed variable tumor control (stable disease / response; TTV: 3/5 (60.0%); Tg: 2/5 (40.0%); RECIST 1.1: 3/5 (60.0%)). All patients undergoing discontinuous PRRT exhibited concordant stable disease upon first follow-up and renewed tumor control upon reinitiating PRRT (RECIST 1.1; decreasing TTV and Tg levels). No Common Terminology Criteria for Adverse Events (CTCAE) Grade 3-5 events occured in both groups.

Conclusion: In advanced radioiodine-refractory DTC, PRRT may be beneficial even after treatment interruptions, without major side effects. Given the small cohort and retrospective design, further prospective studies are needed to optimize PRRT strategies in DTC, in particular in a rechallenge scenario.