Yann Seimbille
Erasmus University Rotterdam, Radiology, Faculty Member
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Background There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular... more
Background There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery. Results Binding of 800CW-TATE could be blocked with DOTA0-Tyr3-octreotate (DOTA-TATE) on cultured SSTR2-positive U2OS cells and was absent in SSTR2 negative U2OS cells. However, strong binding was observed to dead cells, which could no...
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Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, is an important biomarker. Tumor necrosis occurs in most solid tumors due to improperly functioning blood vessels that cannot keep... more
Necrosis only occurs in pathological situations and is directly related to disease severity and, therefore, is an important biomarker. Tumor necrosis occurs in most solid tumors due to improperly functioning blood vessels that cannot keep up with the rapid growth, especially in aggressively growing tumors. The amount of necrosis per tumor volume is often correlated to rapid tumor proliferation and can be used as a diagnostic tool. Furthermore, efficient therapy against solid tumors will directly or indirectly lead to necrotic tumor cells, and detection of increased tumor necrosis can be an early marker for therapy efficacy. We propose the application of necrosis avid contrast agents to detect therapy-induced tumor necrosis. Herein, we advance gallium-68-labeled IRDye800CW, a near-infrared fluorescent dye that exhibits excellent necrosis avidity, as a potential PET tracer for in vivo imaging of tumor necrosis. We developed a reliable labeling procedure to prepare [68Ga]Ga-DOTA-PEG4-I...
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Carbonic anhydrase IX (CAIX) is a tumor-specific and hypoxia-induced biomarker for the molecular imaging of solid malignancies. The nuclear- and optical-imaging of CAIX-expressing tumors have received great attention due to their... more
Carbonic anhydrase IX (CAIX) is a tumor-specific and hypoxia-induced biomarker for the molecular imaging of solid malignancies. The nuclear- and optical-imaging of CAIX-expressing tumors have received great attention due to their potential for clinical applications. Nuclear imaging is a powerful tool for the non-invasive diagnosis of primary and metastatic CAIX-positive tumors and for the assessment of responses to antineoplastic treatment. Intraoperative optical fluorescence imaging provides improved visualization for surgeons to increase the discrimination of tumor lesions, allowing for safer surgical treatment. Over the past decades, many CAIX-targeted molecular imaging probes, based on monoclonal antibodies, antibody fragments, peptides, and small molecules, have been reported. In this review, we outline the recent development of CAIX-targeted probes for single-photon emission computerized tomography (SPECT), positron emission tomography (PET), and near-infrared fluorescence ima...
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Additional file 1. Supplementary data 1: controls in vitro dead/alive cell binding. Supplementary data 2: microscopy. Supplementary data 3: ex vivo binding of 800CW-TATE and to NCI-H69 and CH-157MN tumor sections. Supplementary data 4:... more
Additional file 1. Supplementary data 1: controls in vitro dead/alive cell binding. Supplementary data 2: microscopy. Supplementary data 3: ex vivo binding of 800CW-TATE and to NCI-H69 and CH-157MN tumor sections. Supplementary data 4: SSTR2 IF staining.
Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead... more
Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [18F]FDG-PET and bioluminescence images for complementary detection of tumor viability. Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [111In]3 for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [111In]3-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatme...
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endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity
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Statistical analyses of the biodistribution data of [18F]FPyPEGCBT-c(RGDfK) in nude mice bearing U-87 MG or SKOV-3 subcutaneous tumours a . Figure S1. siRNA-mediated integrin depletions analysis by densitometry. αV, β1, β3 or β5 integrin... more
Statistical analyses of the biodistribution data of [18F]FPyPEGCBT-c(RGDfK) in nude mice bearing U-87 MG or SKOV-3 subcutaneous tumours a . Figure S1. siRNA-mediated integrin depletions analysis by densitometry. αV, β1, β3 or β5 integrin subunits and indicated combinations were knocked-down by siRNA in U-87 MG and SKOV-3 and protein extracts were submitted to immunoblotting using specific antibodies. Expression levels of each integrin were then quantified with a Chemidoc MP. Data are mean fold expression changes in indicated samples as compared to untransfected cells (Unt) ± SD (n = 3). Figure S2. Uptake of [125I]echistatin in cells with selective siRNA-mediated integrin knocked down. U-87 MG and SKOV-3 cells knocked down for αV, β1, β3 or β5 integrin subunits and indicated combinations were incubated with 100 kBq/mL [18F]FPyPEGCBT-c(RGDfK) for 15 to 120 min at 37 °C. Depletions were verified by immunoblotting using specific antibodies as compared to untransfected cells (Unt) and to...
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In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional (18)F prosthetic molecule has been developed. The compound, dubbed [(18)F]FPyPEGCBT, consists of a 2-substituted pyridine... more
In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional (18)F prosthetic molecule has been developed. The compound, dubbed [(18)F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [(18)F]F(-) incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain. [(18)F]FPyPEGCBT could be prepared from its corresponding 2-trimethylammonium triflate precursor (100 °C, 15 min, MeCN) in preparative yields of 11% ± 2 (decay corrected, n = 3) after HPLC purification. However, because the primary radiochemical impurity of the fluorination reaction will not interact with 1,2-aminothiol functionalities, the (18)F prosthetic could be prepared for bioconjugation reactions by way of partial purification on a molecularly imprinted polymer solid-phase extraction cartridge. [(18)F]FPyPEGCBT was used to (18)F-label a cyclo-(RGDfK) analogue which was m...
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Summary Purpose: To evaluate the mean effective radiation dose of 13N-ammonia PET/CT and ECGpulsing CT angiography (CTA) in the evaluation of myocardial perfusion, myocardial blood flow (MBF) and coronary morphology for the identification... more
Summary Purpose: To evaluate the mean effective radiation dose of 13N-ammonia PET/CT and ECGpulsing CT angiography (CTA) in the evaluation of myocardial perfusion, myocardial blood flow (MBF) and coronary morphology for the identification of subclinical CAD. Patients, material, methods: Following rest-stress 13N-ammonia PET/CT perfusion imaging and MBF quantification, ECG-pulsing CTA at a pulse window of 70% of the R-R cycle was performed in ten healthy controls and in sixteen individuals with cardiovascular risk factors. Individual radiation dose exposure for ECG-pulsing CTA was estimated from the dose-length product. Results: PET demonstrated normal perfusion in all study individuals, while hyperemic MBFs during dipyridamole stimulation and the myocardial flow reserve (MFR) in cardiovascular risk individuals were significantly lower than in healthy controls (1.34 ± 0.26 vs. 2.28 ± 0.47 ml/g/min and 1.48 ± 0.39 vs. 3.24 ± 0.81, both p . 0.0001). Further, ECG-pulsing CTA identified ...
Research Interests: Magnetic Resonance Imaging, Positron Emission Tomography, Medicine, Electrocardiography, Adenosine, and 15 moreHumans, Female, Feasibility Studies, Male, Ammonia, Clinical Sciences, Aged, Middle Aged, Coronary Angiography, Adult, Coronary Circulation, Myocardial Perfusion Imaging, Coronary Artery Disease, Exercise Test, and Blood Flow Velocity
Research Interests: Computed Tomography, Microcirculation, Medicine, Cardiovascular Risk, Multivariate Analysis, and 15 moreHumans, Female, Male, Aged, Middle Aged, Endothelial Function, Coronary Angiography, Adult, Myocardium, Cardiovascular Diseases, Coronary Circulation, Coronary Artery Disease, Case Control Studies, Myocardial Blood Flow, and Cardiovascular medicine and haematology
Research Interests: Cardiology, Obesity, Magnetic Resonance Imaging, Positron Emission Tomography, Medicine, and 15 moreOverweight, Humans, Internal Medicine, Hemodynamics, Female, Male, Heart rate, Aged, Middle Aged, Adult, Nuclear Cardiology, Myocardium, Body Weight, Coronary Circulation, and Cardiovascular medicine and haematology
Research Interests: Computed Tomography, Medicine, Molecular Imaging, Cercopithecus aethiops, Cell line, and 15 moreMice, PET imaging, Animals, Ct Scan, Clinical Sciences, European, Epidermal Growth Factor, Epidermal Growth Factor Receptor, Neoplasms, Radiopharmaceuticals, Functional Status, Non small Cell Lung Cancer, Gefitinib, Quinazolines, and Tissue distribution
Research Interests: Obesity, Positron Emission Tomography, Medicine, Humans, Internal Medicine, and 14 moreHemodynamics, Female, Male, Body Mass Index, Aged, Middle Aged, Blood Flow, Circulation, Coronary Circulation, Endocannabinoids, ENDOTHELIUM, Coronary Artery Disease, Case Control Studies, and Cardiovascular medicine and haematology
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Nuclear and optical dual-modality probes can be of great assistance in prostate cancer localization, providing the means for both preoperative nuclear imaging and intraoperative surgical guidance. We developed a series of probes based on... more
Nuclear and optical dual-modality probes can be of great assistance in prostate cancer localization, providing the means for both preoperative nuclear imaging and intraoperative surgical guidance. We developed a series of probes based on the backbone of the established GRPR-targeting radiotracer NeoB. The inverse electron demand of the Diels–Alder reaction was used to integrate the sulfo-cyanine 5 dye. Indium-111 radiolabeling, stability studies and a competition binding assay were carried out. Pilot biodistribution and imaging studies were performed in PC-3 tumor-bearing mice, using the best two dual-labeled probes. The dual-modality probes were radiolabeled with a high yield (>92%), were proven to be hydrophilic and demonstrated high stability in mouse serum (>94% intact labeled ligand at 4 h). The binding affinity for the GRPR was in the nanomolar range (21.9–118.7 nM). SPECT/CT images at 2 h p.i. clearly visualized the tumor xenograft and biodistribution studies, after sca...
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Currently, radiolabeled DOTA-[Tyr3]-octreotate (DOTA-TATE) is most commonly used in the clinic to image and treat neuroendocrine tumors. To further improve tumor uptake, and thus treatment, the amount of radiotracer that can accumulate in... more
Currently, radiolabeled DOTA-[Tyr3]-octreotate (DOTA-TATE) is most commonly used in the clinic to image and treat neuroendocrine tumors. To further improve tumor uptake, and thus treatment, the amount of radiotracer that can accumulate in the tumor might be increased by prolonging the blood circulation time of the radiotracer. To achieve this, we designed Albutate-1, with both DOTA and an albumin-binding domain coupled to TATE via a suitable linker. The aim of this study was to determine the characteristics of the novel radiotracer Albutate-1. A competition binding assay was performed using [111In]In-DOTA-TATE on fresh-frozen SSTR2+ tumor sections. In vitro cell-uptake and internalization of [111In]In-Albutate-1 and [111In]In-DOTA-TATE were determined. The stability of [177Lu]Lu-Albutate-1 was tested. A biodistribution study was performed to provide tumor and organ uptake of [177Lu]Lu-Albutate-1. The biodistribution data was used to determine time-activity curves and the radiation d...
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Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each... more
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.
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Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective... more
Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes (18F-2 and 18F-3) as well as a control probe (18F-1) were specifically designed for PET imaging of legumain activity in tumors. 18F-1, 18F-2, and 18F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" 18F-labeling method. The probes 18F-2 and 18F-3 exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for 18F-2 and 18F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18F-2 + 2 and 18F-3 + 3 at 1 h), while the control probe 18F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (18F-2 + 2 and 18F-3 + 3) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for 18F-2 and 18F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.
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We have prepared the 2‐ and 4‐fluoro derivatives of 16α‐[18F]fluoroestradiol (FES) (4a, b) and 11β‐OMe‐FES (4c, d). Electrophilic substitution of estrone or 11β‐OMe‐estrone with N‐fluoropyridinium salt gave the 2‐and 4‐F derivatives 1,... more
We have prepared the 2‐ and 4‐fluoro derivatives of 16α‐[18F]fluoroestradiol (FES) (4a, b) and 11β‐OMe‐FES (4c, d). Electrophilic substitution of estrone or 11β‐OMe‐estrone with N‐fluoropyridinium salt gave the 2‐and 4‐F derivatives 1, which were converted to the triols 2 and subsequently to the reactive 16β, 17β‐cyclic sulfates 3. Stereoselective opening of the cyclic sulfates via nucleophilic fluorination with Me4NF or [18F]F‐ and removal of the protecting ether and sulfate groups via rapid acid hydrolysis gave 4a‐d or [16α‐18F]‐(4a‐d).
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Targeted therapies, such as radioimmunotherapy (RIT), present a promising treatment option for the eradication of tumor lesions. RIT has shown promising results especially for hematologic malignancies, but the therapeutic efficacy is... more
Targeted therapies, such as radioimmunotherapy (RIT), present a promising treatment option for the eradication of tumor lesions. RIT has shown promising results especially for hematologic malignancies, but the therapeutic efficacy is limited by unfavorable tumor-to-background ratios resulting in high radiotoxicity. Pretargeting strategies can play an important role in addressing the high toxicity profile of RIT. Key to pretargeting is the concept of decoupling the targeting vehicle from the cytotoxic agent and administrating them separately. Studies have shown that this approach has the ability to enhance the therapeutic index as it can reduce side effects caused by off-target irradiation and thereby increase curative effects due to higher tolerated doses. Pretargeted RIT (PRIT) has been explored for imaging and treatment of different cancer types over the years. This review will give an overview of the various targeted therapies in which pretargeting has been applied, discussing PR...
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The pretargeting strategy has recently emerged in order to overcome the limitations of direct targeting, mainly in the field of radioimmunotherapy (RIT). This strategy is directly dependent on chemical reactions, namely bioorthogonal... more
The pretargeting strategy has recently emerged in order to overcome the limitations of direct targeting, mainly in the field of radioimmunotherapy (RIT). This strategy is directly dependent on chemical reactions, namely bioorthogonal reactions, which have been developed for their ability to occur under physiological conditions. The Staudinger ligation, the copper catalyzed azide-alkyne cycloaddition (CuAAC) and the strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC) were the first bioorthogonal reactions introduced in the literature. However, due to their incomplete biocompatibility and slow kinetics, the inverse-electron demand Diels-Alder (IEDDA) reaction was advanced in 2008 by Blackman et al. as an optimal bioorthogonal reaction. The IEDDA is the fastest bioorthogonal reaction known so far. Its biocompatibility and ideal kinetics are very appealing for pretargeting applications. The use of a trans-cyclooctene (TCO) and a tetrazine (Tz) in the reaction encouraged researche...
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Recently, promising results of the antitumor effects were observed in patients with metastatic castration-resistant prostate cancer treated with 177Lu-labeled PSMA-ligands. Radionuclide therapy efficacy may even be improved by using the... more
Recently, promising results of the antitumor effects were observed in patients with metastatic castration-resistant prostate cancer treated with 177Lu-labeled PSMA-ligands. Radionuclide therapy efficacy may even be improved by using the alpha emitter Ac-225. Higher efficacy is claimed due to high linear energy transfer specifically towards PSMA positive cells, causing more double-strand breaks. This study aims to manufacture [225Ac]Ac-PSMA-I&T according to good manufacturing practice guidelines for the translation of [225Ac]Ac-PSMA-I&T into a clinical phase 1 dose escalation study. Quencher addition during labeling was investigated. Quality control of [225Ac]Ac-PSMA-I&T was based on measurement of Fr-221 (218 keV), in equilibrium with Ac-225 in approximately six half-lives of Fr-221 (T½ = 4.8 min). Radio-(i)TLC methods were utilized for identification of the different radiochemical forms, gamma counter for concentration determination, and HPGe-detector for the detection of the radio...
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Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for... more
Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand...
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Simple and efficient synthesis of dual-modality imaging agents for preoperative surgical planning and intraoperative surgical guidance.
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We herein describe a flexible synthesis of a small library of 68Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were... more
We herein describe a flexible synthesis of a small library of 68Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were successfully synthesized and labeled with the positron emitter gallium-68. Cross-ligation between the pre-labeled bifunctional chelators (BFCs) and the 1,2-aminothiol-acetazolamide derivatives (8 and 9) yielded six new 68Ga-labeled CAIX ligands with high radiochemical yields. The click reaction conditions were optimized to improve the reaction rate for applications with short half-life radionuclides. Overall, our methodology allows for a simple and efficient radiosynthetic route to produce a variety of 68Ga-labeled imaging agents for tumor hypoxia.
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Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [F]-F-85380-A (F-A-85380), an α4β2 nicotinic... more
Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BP, corresponding to the receptor availability) i...
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The aims of this study were to assess the intraindividual performance of F-fluorocholine (FCH) and C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging... more
The aims of this study were to assess the intraindividual performance of F-fluorocholine (FCH) and C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management. Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA] ≤3 ng/mL), primary radiotherapy (n = 8, prostate-specific antigen ≤5 ng/mL), or radical prostatectomy + salvage radiotherapy (n = 15) underwent ACE and FCH PET-CT (n = 29) or PET-MRI (n = 4) studies in a randomized sequence 0 to 21 days apart. The detection rate for ACE was 66% and for FCH was 60%. Results were concordant in 79% of the cases (26/33) and discordant in 21% (retroperitoneal, n = 5; pararectal, n = 1; and external iliac nodes, n = 1). After a median FU of 41 months (n = 32, 1 patient lost to FU), the site of relapse was correctly identified by ACE and FCH in...
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Hypoxia, a condition of insufficient oxygen availability to support metabolism, occurs when the vascular supply is interrupted, as in stroke. The identification of the hypoxic and viable tissue in stroke as compared with irreversible... more
Hypoxia, a condition of insufficient oxygen availability to support metabolism, occurs when the vascular supply is interrupted, as in stroke. The identification of the hypoxic and viable tissue in stroke as compared with irreversible lesions (necrosis) has relevant implications for the treatment of ischemic stroke. Traditionally, imaging by positron emission tomography (PET), using 15O-based radiotracers, allowed the measurement of perfusion and oxygen extraction in stroke, providing important insights in its pathophysiology. However, these multitracer evaluations are of limited applicability in clinical settings. More recently, specific tracers have been developed, which accumulate with an inverse relationship to oxygen concentration and thus allow visualizing the hypoxic tissue non invasively. These belong to two main groups: nitroimidazoles, and among these the 18F-Fluoroimidazole (18F-FMISO) is the most widely used, and the copper-based tracers, represented mainly by Cu-ATSM. While these tracers have been at first developed and tested in order to image hypoxia in tumors, they have also shown promising results in stroke models and preliminary clinical studies in patients with cardiovascular disorders, allowing the detection of hypoxic tissue and the prediction of the extent of subsequent ischemia and clinical outcome. These tracers have therefore the potential to select an appropriate subgroup of patients who could benefit from a hypoxia-directed treatment and provide prognosis relevant imaging. The molecular imaging of hypoxia made important progress over the last decade and has a potential for integration into the diagnostic and therapeutic workup of patients with ischemic stroke.