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Prospective comparison of (4S)-4-(3-18F-fluoropropyl)-l-glutamate versus 18F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study
摘要： Purpose (4S)-4-(3-18F-Fluoropropyl)-L-glutamate (FSPG) positron emission tomography (PET) reflects system xC- (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC. Methods The performance of FSPG in detecting PDAC metastases was compared with that of 18F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later. Results In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9–14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI ?1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70–4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis. Conclusion FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.
关键词： FSPG,Pancreatic cancer,Positron emission tomography,Liver metastases,xC transporter system
更新于2025-11-21 11:24:58
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Targeting carbon nanotubes based on IGF-1R for photothermal therapy of orthotopic pancreatic cancer guided by optical imaging
摘要： Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity. Single-walled carbon nanotubes (SWNTs) can remedy the above inadequacies. Herein, we report our water-soluble, bio-stable and low-toxicity SWNTs with excellent photothermal conversion efficiency. Specific modifications can enable visualization of the aggregate characteristics of SWNTs at the macroscopic or microscopic level in tumors. The dye-conjugated SWNTs bound with targeting antibodies that can induce them specifically targeting to pancreatic tumors for purposes of performing dyes imaging-guided cytotoxic PTT. PTT using this method achieves precise and excellent curative effects with minimal adverse effects, thus providing a promising strategy for anticancer therapy.
关键词： Single-walled carbon nanotubes,Imaging,IGF-1R,Pancreatic cancer,Photothermal therapy
更新于2025-09-23 15:23:52
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Interventional Photothermal Therapy Enhanced Brachytherapy: A New Strategy to Fight Deep Pancreatic Cancer
摘要： Photothermal–radiotherapy (PT–RT) is an effective strategy for relieving hypoxia-related radiotherapy resistance and inducing tumor-specific cell apoptosis/necrosis. Nevertheless, limited tissue penetration of near-infrared (NIR) laser and the serious side effects of high-dose radiation severely hinder its applications for deep tumors. An interventional photothermal–brachytherapy (IPT–BT) technology is proposed here for the internal site-specific treatment of deep tumors. This technology utilizes a kind of biodegradable honeycomb-like gold nanoparticles (HGNs) acting as both internal photothermal agents and radiosensitizers. A high tumor inhibition rate of 96.6% is achieved in SW1990 orthotopic pancreatic tumor-bearing mice by HGNs-mediated IPT–BT synergistic therapy. Interestingly, this approach effectively causes double-stranded DNA damage and improves the oxygen supply and the penetration of nanoparticles inside the tumor. Therefore, it is believed that this strategy may open up a new avenue for PT–RT synergistic therapy of deep malignant tumors and has a significant impact on the future clinical translation.
关键词： photothermal therapy,pancreatic cancer,biodegradable,interventional,brachytherapy,honeycomb-like gold
更新于2025-09-23 15:22:29
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Staging laparoscopy with ultrasound and near-infrared fluorescence imaging to detect occult metastases of pancreatic and periampullary cancer
摘要： Introduction Up to 38% of pancreatic and periampullary cancer patients undergoing curative intended surgery turn out to have incurable disease. Therefore, staging laparoscopy (SL) prior to laparotomy is advised to spare patients the morbidity, inconvenience and expense of futile major surgery. The aim of this study was to assess the added value of SL with laparoscopic ultrasonography (LUS) and laparoscopic near-infrared fluorescence imaging (LFI). Methods All patients undergoing curative intended surgery of pancreatic or periampullary cancer were included prospectively in this single arm study. Patients received an intravenous infusion of 10 mg indocyanine green (ICG) one or two days prior to surgery to allow LFI. Suspect lesions were analyzed via biopsy or resection. Follow-up visits after surgery occurred every three months. Results A total of 25 patients were included. Suspect lesions were identified in 7 patients: liver metastases (n = 2; identified by inspection, LUS, and LFI), peritoneal metastases (n = 1; identified by inspection only), and benign lesions (n = 4; identified by inspection or LUS). Quality of LFI was good in 67% (10/15) of patients dosed one day and 89% (8/9) dosed two days prior to surgery. A futile laparotomy was averted in 3 patients (12%). Following SL the primary tumor was resected in 20 patients. Two patients (10%) developed metastases within 3 months after resection. Conclusions Despite current preoperative imaging modalities metastases are still identified during surgery. This study shows limited added value of LUS during SL in patients with pancreatic or periampullary cancer. LFI was of added value due to its high negative predictive value in case of suspect hepatic lesions identified by inspection.
关键词： near-infrared fluorescence imaging,staging laparoscopy,laparoscopic ultrasonography,pancreatic cancer,periampullary cancer,indocyanine green
更新于2025-09-23 15:21:01
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<sup>86/90</sup> Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics
摘要： Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair 86/90Y as a theranostic agent against pancreatic cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of 86Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.
关键词： pancreatic cancer,yttrium-86,radioimmunotherapy,tissue factor,yttrium-90,theranostics,positron emission tomography (PET)
更新于2025-09-23 15:21:01
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Label-Free Biosensing Method for the Detection of a Pancreatic Cancer Biomarker Based on Dielectrophoresis Spectroscopy
摘要： We show that negative dielectrophoresis (DEP) spectroscopy is an effective transduction mechanism of a biosensor for the diagnosis and prognosis of pancreatic cancer using the biomarker CA 19-9. A substantial change in the negative DEP force applied to functionalized polystyrene microspheres (PM) was observed with respect to both the concentration level of the pancreatic cancer biomarker CA 19-9 and the frequency of the electric field produced by a pearl shaped interdigitated gold micro-electrode. The velocity of repulsion of a set of PM functionalized to a monoclonal antibody to CA 19-9 was calculated for several concentration cutoff levels of CA 19-9, including 0 U/mL and 37 U/mL, at the frequency range from 0.5 to 2 MHz. The velocity of repulsion of the PM from the electrode was determined using a side illumination and an automated software using a real-time image processing technique that captures the Mie scattering from the PM. Since negative DEP spectroscopy is an effective transduction mechanism for the detection of the cutoff levels of CA 19-9, it has the potential to be used in the early stage diagnosis and in the prognosis of pancreatic cancer.
关键词： spectroscopy,pancreatic cancer,dielectrophoresis,label free,bioelectronics
更新于2025-09-23 15:21:01
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Peroral cholangioscopya??guided probe-based confocal laser endomicroscopy for preoperative diagnosis of pancreatic cancer in a patient with surgically altered anatomy
摘要： A 79-year-old man was referred to our hospital because of jaundice. He had previously undergone Billroth-II gastrectomy for gastric cancer. Contrast CT showed a mass lesion in the pancreatic head with contrast effects and invasion of the distal bile ducts. Additionally, ERCP was performed to obtain more detail. Because of the patient’s prior gastrectomy, ERCP was performed with a short-type single-balloon enteroscope, SIF-H290S (Olympus Medical Systems, Tokyo, Japan) with a working length of 152 cm and channel diameter of 3.2 mm. Cholangiography showed a defect in the distal bile duct. The procedure was then completed with fluoroscopy-guided biopsy of the bile duct. However, the size of the biopsy sample was insufficient to enable a conclusive diagnosis. ERCP was performed again 2 weeks later. With the aim of improving diagnostic ability, a CF-H260AI colonoscope (Olympus Medical Systems Corporation, Tokyo, Japan) with a working length of 133 cm and channel diameter of 3.7 mm was used to perform peroral cholangioscopy (POCS) guided by SpyGlass DS (Boston Scientific Corp, Marlborough, Mass, USA) fluorescein-dripping laser endomicroscopy (pCLE) probe-based confocal (CholangioFlex, Cellvizio; Mauna Kea Technologies, Inc, Paris, France) and POCS-guided biopsy. When the papilla was reached, it was possible to insert the cholangioscope inside the bile duct. Both findings suggested cancer, with POCS showing an irregular, hemorrhagic, papillary protrusion lesion, and pCLE showing a dark ductal structure with irregular margins. POCS confirmed that the bile ducts at nonlesion sites had normal mucosa, and pCLE showed a reticular network of thin, dark, branching bands, considered to be normal. POCS-guided biopsies were performed at both lesion and nonlesion sites. In contrast to the initial fluoroscopy-guided biopsy performed with ERCP, a sample of sufficient size was collected by the POCS-guided biopsy. The biopsy samples contained atypical cells with hyperchromatic nuclei and eosinophilic cytoplasm. Similarly to the pCLE findings, these formed a ductal structure with irregular margins. The nuclei showed marked variations in size, irregular morphology, and irregular arrangement, indicating adenocarcinoma. Biopsy specimens from normal bile ducts showed no malignancy. Therefore, a preoperative diagnosis of pancreatic cancer was made, and pancreatoduodenectomy was performed. The histopathologic findings from the surgical samples were similar to those from the POCS biopsy tissue samples, and irregular, invasive proliferation by atypical bile ducts with eosinophilic cytoplasm was found, confirming pancreatic cancer.
关键词： pancreatic cancer,probe-based confocal laser endomicroscopy,surgically altered anatomy,peroral cholangioscopy
更新于2025-09-23 15:19:57
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Laser-assisted 3D bioprinting of exocrine pancreas spheroid models for cancer initiation study
摘要： Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas. It has shown a poor prognosis and a rising incidence in the developed world. Other pathologies associated with this tissue include pancreatitis, a risk condition for pancreatic cancer. The onset of both pancreatitis and pancreatic cancer follows a common pattern: exocrine pancreatic acinar cells undergo a transdifferentiation to duct cells that triggers a 3D restructuration of the pancreatic tissue. However, the exact mechanism underlying this process remains partially undefined. Further understanding the cellular events leading to PDAC could open new avenues in the development of novel therapeutic approaches. Since current 2D cell culture models fail to mimic the tridimensional complexity of the pancreatic tissue, new in vitro models are urgently needed. Here, we generated 3D pancreatic cell spheroid arrays using laser-assisted bioprinting (LAB) and characterized their phenotypic evolution over time through image analysis and phenotypic characterization. We show that these bioprinted spheroids, composed of both acinar and ductal cells, can replicate the initial stages of PDAC development. This bioprinted miniaturized spheroid-based array model should prove useful for the study of the internal and external factors that contribute to the formation of precursor PDAC lesions and to cancer progression, and may therefore shed light on future PDAC therapy strategies.
关键词： pancreatic cancer,Laser-assisted bioprinting,early lesions,in vitro cancer model,cancer initiation
更新于2025-09-19 17:13:59
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Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions
摘要： Background & Aims: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from non-mucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. Methods: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from non-mucinous lesions with that of measurement of CEA and cytology analysis. Results: The mean size of dominant cysts was 36.4±15.7 mm and the mean duration of nCLE imaging was 7.3±2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature, based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs non-mucinous cysts than the standard method (P<.001). The overall incidence of post-procedure acute pancreatitis was 3.5% (5/144); all episodes were mild, based on the revised Atlanta criteria. Conclusions: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from non-mucinous PCLs. ClincialTrials.gov no: NCT02516488.
关键词： pancreatic cancer,risk,pathology,INDEX study,diagnosis
更新于2025-09-16 10:30:52
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Utility of PET/CT in diagnosis, staging, assessment of resectability and metabolic response of pancreatic cancer
摘要： Pancreatic cancer is one of the most common gastrointestinal tumors, with its incidence staying at a high level in both the United States and China. However, the overall 5-year survival rate of pancreatic cancer is still extremely low. Surgery remains the only potential chance for long-term survival. Early diagnosis and precise staging are crucial to make proper clinical decision for surgery candidates. Despite advances in diagnostic technology such as computed tomography (CT) and endoscopic ultrasound, diagnosis, staging and monitoring of the metabolic response remain a challenge for this devastating disease. Positron emission tomography/CT (PET/CT), a relatively novel modality, combines metabolic detection with anatomic information. It has been widely used in oncology and achieves good results in breast cancer, lung cancer and lymphoma. Its utilization in pancreatic cancer has also been widely accepted. However, the value of PET/CT in pancreatic disease is still controversial. Will PET/CT change the treatment strategy for potential surgery candidates? What kind of patients benefits most from this exam? In this review, we focus on the utility of PET/CT in diagnosis, staging, and assessment of resectability of pancreatic cancer. In addition, its ability to monitor metabolic response and recurrence after treatment will be emphasis of discussion. We hope to provide answers to the questions above, which clinicians care most about.
关键词： Staging,Pancreatic cancer,Metabolic response,Position emission tomography/computed tomography,Diagnosis
更新于2025-09-10 09:29:36