Abstract:
:Early detection of pancreatic ductal adenocarcinoma (PDAC) represents the most significant step toward the treatment of this aggressive lethal disease. Previously, we engineered a preclinical Thy1-targeted microbubble (MBThy1) contrast agent that specifically recognizes Thy1 antigen overexpressed in the vasculature of murine PDAC tissues by ultrasound (US) imaging. In this study, we adopted a single-chain variable fragment (scFv) site-specific bioconjugation approach to construct clinically translatable MBThy1-scFv and test for its efficacy in vivo in murine PDAC imaging, and functionally evaluated the binding specificity of scFv ligand to human Thy1 in patient PDAC tissues ex vivo. MATERIALS AND METHODS:We recombinantly expressed the Thy1-scFv with a carboxy-terminus cysteine residue to facilitate its thioether conjugation to the PEGylated MBs presenting with maleimide functional groups. After the scFv-MB conjugations, we tested binding activity of the MBThy1-scFv to MS1 cells overexpressing human Thy1 (MS1Thy1) under liquid shear stress conditions in vitro using a flow chamber setup at 0.6 mL/min flow rate, corresponding to a wall shear stress rate of 100 seconds, similar to that in tumor capillaries. For in vivo Thy1 US molecular imaging, MBThy1-scFv was tested in the transgenic mouse model (C57BL/6J - Pdx1-Cre; KRas; Ink4a/Arf) of PDAC and in control mice (C57BL/6J) with L-arginine-induced pancreatitis or normal pancreas. To facilitate its clinical feasibility, we further produced Thy1-scFv without the bacterial fusion tags and confirmed its recognition of human Thy1 in cell lines by flow cytometry and in patient PDAC frozen tissue sections of different clinical grades by immunofluorescence staining. RESULTS:Under shear stress flow conditions in vitro, MBThy1-scFv bound to MS1Thy1 cells at significantly higher numbers (3.0 ± 0.8 MB/cell; P < 0.01) compared with MBNontargeted (0.5 ± 0.5 MB/cell). In vivo, MBThy1-scFv (5.3 ± 1.9 arbitrary units [a.u.]) but not the MBNontargeted (1.2 ± 1.0 a.u.) produced high US molecular imaging signal (4.4-fold vs MBNontargeted; n = 8; P < 0.01) in the transgenic mice with spontaneous PDAC tumors (2-6 mm). Imaging signal from mice with L-arginine-induced pancreatitis (n = 8) or normal pancreas (n = 3) were not significantly different between the two MB constructs and were significantly lower than PDAC Thy1 molecular signal. Clinical-grade scFv conjugated to Alexa Fluor 647 dye recognized MS1Thy1 cells but not the parental wild-type cells as evaluated by flow cytometry. More importantly, scFv showed highly specific binding to VEGFR2-positive vasculature and fibroblast-like stromal components surrounding the ducts of human PDAC tissues as evaluated by confocal microscopy. CONCLUSIONS:Our findings summarize the development and validation of a clinically relevant Thy1-targeted US contrast agent for the early detection of human PDAC by US molecular imaging.
journal_name
Invest Radioljournal_title
Investigative radiologyauthors
Bam R,Daryaei I,Abou-Elkacem L,Vilches-Moure JG,Meuillet EJ,Lutz A,Marinelli ER,Unger EC,Gambhir SS,Paulmurugan Rdoi
10.1097/RLI.0000000000000697subject
Has Abstractpub_date
2020-11-01 00:00:00pages
711-721issue
11eissn
0020-9996issn
1536-0210journal_volume
55pub_type
杂志文章abstract:OBJECTIVE:The aim of this study was to evaluate the potential of iterative metal artifact reduction (IMAR) for the improvement of computed tomography (CT)-based position emission tomography (PET) attenuation correction in the vicinity of metal implants and compare it with dual-energy-based metal artifact reduction stra...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000306
更新日期:2017-01-01 00:00:00
abstract::Breast calcification diagnosis was studied by using clinical findings and computerized image processing of a mammogram in a network of trained expert learning systems (Outcome Advisor [OA]). The system was tested with records not used for training and performance was compared with radiologist. The network was 72% accu...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199106000-00004
更新日期:1991-06-01 00:00:00
abstract::Surgical resection is the standard of care for colorectal metastases isolated to the liver. However, only 10-25% of the patients are eligible for resection because of extent and location of the disease in the liver or concurrent medical conditions. Image-guided radiofrequency (RF) ablation is a minimally invasive tech...
journal_title:Investigative radiology
pub_type: 杂志文章,评审
doi:10.1097/00004424-200411000-00007
更新日期:2004-11-01 00:00:00
abstract::The biliary and urinary excretion of sodium tyropanoate (Bilopaque) and sodium ipodate (Oragrafin) were studied in unanesthetized bile-fistula dogs using stepwise, increasing, intravenous infusions of the contrast materials. A constant intravenous infusion of sodium taurocholate was administered at the rate of either ...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-197701000-00017
更新日期:1977-01-01 00:00:00
abstract::Dense cavitary "photopenia" was observed on 21 of 200 consecutive stress perfusion scintigrams. A prominent finding in many cases, it sometimes occupied only a portion of the region overlying the ventricular cavity, was often seen in some projections and not others, and was frequently adjacent to myocardial perfusion ...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198507000-00009
更新日期:1985-07-01 00:00:00
abstract::A series of 5-hydroxyacylamino-2,4,6-triiodo-N,N'-hydroxy-alkyl-isophtalamides was prepared in order to study the structural requirements for high water solubility and low toxicity. Among the amides substituted by 2-hydroxyethyl; 2,3-dihydroxypropyl; 1,3-dihydroxypropyl-; and 1,1-dihydroxy-methyl-2-oxyethyl- groups, t...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198011001-00065
更新日期:1980-11-01 00:00:00
abstract:PURPOSE:To prospectively determine the accuracy of 1.5 Tesla (T) and 3 T magnetic resonance angiography (MRA) versus digital subtraction angiography (DSA) in the depiction of infrageniculate arteries in patients with symptomatic peripheral arterial disease. PATIENTS AND METHODS:A prospective 1.5 T, 3 T MRA, and DSA co...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/01.rli.0000262581.52315.ef
更新日期:2007-06-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:To determine whether vascular endothelial growth factor (VEGF) is a histopathological factor influencing contrast enhancement of hepatocellular carcinoma (HCC) on computed tomography (CT). METHODS:Twenty-two nodular HCCs underwent multiphase helical CT and surgery. Tumor size, histological gra...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-200108000-00008
更新日期:2001-08-01 00:00:00
abstract::Human gallstones were surgically placed into the gallbladders of 200 swine. Eight of these swine were used as a prospective series to verify that the placement and presence of human gallstones in their gallbladders caused no significant pathologic changes in the gallbladder and that the gallstones were not spontaneous...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198902000-00005
更新日期:1989-02-01 00:00:00
abstract::Over the past 120 years, continuous developments in medical imaging has improved diagnosis and treatment for many diseases and has thereby improved treatment outcome and quality of life of many patients. The number of computed tomography (CT) examinations is today increasing by 4% per year worldwide, for a total of ap...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000696
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVES:Ferumoxytol, an intravenous iron supplement, can be used in off-label mode as a contrast agent in magnetic resonance imaging. The aim of this study was to assess whether ferumoxytol can be used as a marker of inflammation in animal models of acute and chronic inflammatory kidney diseases. MATERIAL AND METHO...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000209
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVES:The aims of this study were to present a deep learning approach for the automated classification of multiple sclerosis and its mimics and compare model performance with that of 2 expert neuroradiologists. MATERIALS AND METHODS:A total of 268 T2-weighted and T1-weighted brain magnetic resonance imagin scans ...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000735
更新日期:2020-10-26 00:00:00
abstract:RATIONALE AND OBJECTIVES:To assess the potential of magnetic resonance imaging (MRI) for evaluating the evolution of tumor necrosis, the authors evaluated 28 VX2 carcinomas inoculated in the thigh muscles of rabbits. METHODS:MRI of VX2 carcinomas at 2.0 T was done with spin-echo technique 1 week (14 tumors) and 3 week...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199301000-00010
更新日期:1993-01-01 00:00:00
abstract::Video dilution technique (VDT) is currently performed in conjunction with routine cerebral angiography to determine carotid blood flow in humans. Preliminary results indicate that the blood flows (as a percentage of cardial output) of the common, internal, and external carotid arteries are 8.5%, 5.5%, and 3.0%, respec...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198105000-00004
更新日期:1981-05-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:Interstitial laser photocoagulation (ILP) causes localized tissue necrosis. This study was performed to determine 1) whether the changes seen on computed tomography (CT) correspond to the necrosis pathologically, and 2) which CT technique best shows the necrosis. METHODS:Eighteen Wistar rats h...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199312000-00014
更新日期:1993-12-01 00:00:00
abstract:OBJECTIVES:X-ray computed tomography (CT) using phase contrast can provide images with greatly enhanced soft-tissue contrast in comparison to conventional attenuation-based CT. We report on the first scan of a human specimen recorded with a phase-contrast CT system based on an x-ray grating interferometer and a convent...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0b013e3181e21866
更新日期:2010-07-01 00:00:00
abstract::A prospective, randomized study of the potential protective effects of corticosteroids administered as pretreatment against contrast material (CM) reactions is reported. Patients (n = 6,763) from multiple institutions received either a single dose of steroids (32 mg of oral methylprednisolone, approximately 2 hours be...
journal_title:Investigative radiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00004424-198809001-00035
更新日期:1988-09-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:To evaluate the effect of the transverse ligament on translation of the menisci. METHODS:Six cadaveric knees were examined by MR imaging inside a positioning device before and after transecting the transverse ligament. The knees were examined at various positions: extension, 30 degrees of flex...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199909000-00002
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating dis...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000256
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to elucidate the mechanism of hepatic parenchyma-specific contrast of Sonazoid (microbubble contrast agent) using microscopic techniques. MATERIALS AND METHODS:Sonazoid was intravenously injected into rats to investigate the microbubble dynamics and distribution within hepatic...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0b013e31805f2682
更新日期:2007-09-01 00:00:00
abstract::Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxyge...
journal_title:Investigative radiology
pub_type: 杂志文章,评审
doi:10.1097/00004424-199911000-00004
更新日期:1999-11-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:Bolus injection of iodinated contrast media has been observed to alter myocardial mechanical function, but the consequences on cellular metabolism are poorly documented. Modifications of metabolic parameters (intracellular pH as well as adenosine triphosphate [ATP], phosphocreatine, and inorgan...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199501000-00001
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVES:The aims of this study were to investigate and validate quantitative susceptibility mapping (QSM) for lesional iron quantification in cerebral cavernous malformations (CCMs). MATERIALS AND METHODS:Magnetic resonance imaging studies were performed in phantoms and 16 patients on a 3-T scanner. Susceptibility ...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/RLI.0000000000000043
更新日期:2014-07-01 00:00:00
abstract::Proposed causes of renal papillary necrosis (RPN) include tubular toxicity due to hyperconcentration of toxins in the renal medulla and vasoconstriction of medullary vessels with ischemic necrosis. The authors studied these mechanisms in bromoethylamine hydrobromide-induced RPN in rats by microvascular and tubular mic...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198103000-00006
更新日期:1981-03-01 00:00:00
abstract:PURPOSE:We sought to develop a robotic system for computed tomography (CT)-guided biopsy to validate the feasibility, accuracy, and efficacy of the system using phantom tests. MATERIALS AND METHODS:Ten peas (mean diameter 9.9+/-0.4 mm) embedded within a gel phantom were selected for biopsy. Once the best access was de...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/01.rli.0000155285.05672.cf
更新日期:2005-04-01 00:00:00
abstract::Lymphangiograms of canine cardiac and pulmonary efferent mediastinal lymphatics were made by cannulation and injection of Ethiodol. Injections were made singly and serially. The mediastinal lymphatics and lymph nodes, which constitute the pathways of drainage of the heart and lungs, were delineated from the point of c...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-197901000-00012
更新日期:1979-01-01 00:00:00
abstract::Blood samples from previous contrast reactors and nonreactor controls were incubated with diatrizoate and several contrast analogues. Total complement levels were assayed. All the agents caused complement activation generally proportional to their concentration. Reactors' sera responded to lower concentrations of cont...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-198307000-00018
更新日期:1983-07-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:To present the results of two studies conducted to evaluate the pharmacokinetics and safety of iomeprol in healthy volunteers and in patients with various degrees of renal impairment. METHODS:In these two open-label, single-dose, phase I studies, a 50-mL dose of iomeprol 400 was administered i...
journal_title:Investigative radiology
pub_type: 临床试验,杂志文章
doi:10.1097/00004424-200106000-00002
更新日期:2001-06-01 00:00:00
abstract::A nonionic contrast medium (iohexol) was evaluated for safety and efficacy in pediatric angiocardiography in this study of 15 patients, age 6 to 82 months. Patients carried a preliminary diagnosis of congenital heart disease. Subjects were injected with iohexol, 350 mg iodine/ml of solution with an average volume of 2...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:To analyze changes in Doppler ultrasound variables of the portal vein in relation to liver biopsy findings, the authors performed a prospective study of 316 Doppler ultrasound examinations in the first 2 weeks after orthotopic liver transplantation on 23 patients. METHODS:Recordings were obtai...
journal_title:Investigative radiology
pub_type: 杂志文章
doi:10.1097/00004424-199612000-00007
更新日期:1996-12-01 00:00:00