- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Initial evaluation of <scp>PET</scp> / <scp>CT</scp> with <sup>18</sup> F‐ <scp>FSU</scp> ‐880 targeting prostate‐specific membrane antigen in prostate cancer patients
摘要： This first-in-man study was carried out to evaluate the safety, whole-body distribution, dose estimation, and lesion accumulation of 18F-FSU-880, a newly developed probe targeting prostate-specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole-body PET/computed tomography (CT) with 18F-FSU-880. Blood and urine were analyzed before and after PET/CT. Accumulation of 18F-FSU-880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. 18F-FSU-880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well-controlled and inactive. The PET/CT with 18F-FSU-880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of 18F-FSU-880 PET/CT in the management of prostate cancer patients.
关键词： dosimetry,prostate cancer,prostate-specific membrane antigen,positron emission tomography/computed tomography,fluorine-18
更新于2025-09-23 15:23:52
-
Application of Fluorine-18-Deoxyglucose Positron Emission Tomography and Gallium Scan for Assessment in a Patient With Adult-Onset Still's Disease
摘要： A 53-year-old female patient suffered from pain in almost her entire body, particularly the joints. Chest computed tomography revealed multiple lymphadenopathies over cervical, mediastinal, and axillary areas. A fluorine-18-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed increased FDG uptake in many lymph nodes and the spleen. Lymphoma was suspected. However, the result of a biopsy showed no malignancy, and the gallium-67 citrate scan showed no gallium-avid tumor throughout the whole body. Adult-onset Still's disease was diagnosed and the patient responded well to steroid therapy. The follow-up PET/CT six months later showed complete remission of the FDG-avid lesions seen in the previous PET/CT. Our study suggests that FDG PET/CT combined with gallium-67 scan may be helpful in diagnosing patients with adult-onset Still's disease. In addition, the use of FDG PET/CT alone may be useful for the evaluation of disease distribution, disease activity, and therapeutic response.
关键词： fluorine-18-deoxyglucose,Adult-onset Still's disease,positron emission tomography/computed tomography,gallium-67
更新于2025-09-23 15:22:29
-
Modular medical imaging agents based on azidea??alkyne Huisgen cycloadditions: Synthesis and prea??clinical evaluation of 18Fa??labeled PSMAa??tracers for prostate cancer imaging.
摘要： The seminal contribution of Rolf Huisgen to develop the [3+2]-cycloaddition of 1,3-dipolar compounds, its azide-alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide-alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to preclinical in vivo evaluation of fluorine-18– labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t? = 109.7 min). Preclinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]-cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.
关键词： prostate specific membrane antigen,positron emission tomography,fluorine-18,azide-alkyne Huisgen cycloaddition,modular imaging agents
更新于2025-09-23 15:19:57
-
Identification, Characterization, and Optimization of Integrin αvβ6-Targeting Peptides from a One-Bead One-Compound (OBOC) Library: Towards the Development of Positron Emission Tomography (PET) Imaging Agents
摘要： The current translation of peptides identified through the one-bead one-compound (OBOC) technology into positron emission tomography (PET) imaging agents is a slow process, with a major delay between ligand identification and subsequent lead optimization. This work aims to streamline the development process of 18F-peptide based PET imaging agents to target the integrin αvβ6. By directly identify αvβ6–targeting peptides from a 9-mer 4-fluorobenzoyl peptide library using the on-bead two-color (OBTC) cell-screening assay, a total of 185 peptide beads were identified and 5 beads sequenced for further evaluation. The lead peptide 1 (VGDLTYLKK(FB), IC50 = 0.45 ± 0.06 μM, 25% stable in serum at 1 h) was further modified at the N-, C-, and bi-termini. C-terminal PEGylation increased the metabolic stability (>95% stable), but decreased binding affinity (IC50 = 3.7 ± 1 μM) was noted. C-terminal extension (1i, VGDLTYLKK(FB)KVART) significantly increased binding affinity for integrin αvβ6 (IC50 = 0.021 ± 0.002 μM), binding selectivity for αvβ6-expressing cells (3.1 ± 0.8:1), and the serum stability (>99% stable). Our results demonstrate the challenges in optimizing OBOC-derived peptides, indicate both termini of 1 are sensitive to modifications, and show that further modification of 1 is necessary to demonstrate utility as an 18F-peptide imaging agent.
关键词： Fluorine-18,integrin αvβ6,affinity,one-bead one-compound (OBOC),library screening,solid-phase radiolabeling,positron emission tomography (PET),selectivity
更新于2025-09-19 17:15:36
-
Diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a meta-analysis
摘要： Background: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is considered a useful non-invasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18F-FDG-PET/CT for malignant pulmonary nodules. Methods: A computerized research, including published articles from 2012 and 2017, was carried out. 18F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. Results: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794–0.843), 0.624 (95% CI: 0.582–0.665), 2.190 (95% CI: 1.950–2.440), 0.290 (95% CI: 0.250–0.330), 0.802 (95% CI: 0.783–0.819), 0.652 (95% CI: 0.618–0.684) and 0.649 (95% CI: 0.625–0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. Conclusions: The results suggest 18F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.
关键词： Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT),solitary pulmonary nodules (SPNs),lung cancer
更新于2025-09-19 17:15:36
-
[Methods in Molecular Biology] Cancer Metabolism Volume 1928 (Methods and Protocols) || Imaging Cancer Metabolism with Positron Emission Tomography (PET)
摘要： Positron emission tomography (PET) enables the noninvasive spatiotemporal analysis of cancer metabolism in vivo. Both natural and nonnatural PET tracers have been developed to assess metabolic pathways during tumorigenesis, cancer progression, and metastasis. Here we describe the dynamic in vivo PET/CT imaging of the glucose analogue [18F]fluoro-2-deoxy-D-glucose (FDG), taking into consideration the methodology for alternative metabolic PET substrates.
关键词： FDG,Fluorine-18,Imaging,Positron emission tomography,PET,Carbon-11,Fluorodeoxyglucose,Mouse
更新于2025-09-19 17:15:36
-
Synthesis, radiolabelling and initial biological characterisation of <sup>18</sup> F-labelled xanthine derivatives for PET imaging of Eph receptors
摘要： Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for molecular imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC50 values in the low nanomolar range (1–40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain. Based on lead compound 1, we designed two fluorine-18-labelled receptor tyrosine kinase inhibitors ([18F]2/3) as potential tracers for positron emission tomography (PET). Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the methyl group at the uracil residue ([18F]3) rather than the methyl group of the phenoxy moiety ([18F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [18F]2 and [18F]3 and the respective tosylate precursors as well as a labelling procedure to insert fluorine-18. After radiolabelling, both radiotracers were obtained in approximately 5% radiochemical yield with high radiochemical purity (>98%) and a molar activity of >10 GBq μmol?1. In line with the docking studies, first cell experiments revealed specific, time-dependent binding and uptake of [18F]3 to EphA2 and EphB4-overexpressing A375 human melanoma cells, whereas [18F]2 did not accumulate at these cells. Since both tracers [18F]3 and [18F]2 are stable in rat blood, the novel radiotracers might be suitable for in vivo molecular imaging of Eph receptors with PET.
关键词： xanthine derivatives,molecular imaging,positron emission tomography (PET),fluorine-18-labelled,Eph receptor tyrosine kinases
更新于2025-09-19 17:13:59
-
Labeling Single Domain Antibody Fragments with Fluorine-18 Using 2,3,5,6-Tetrafluorophenyl 6-[ <sup>18</sup> F]Fluoronicotinate Resulting in High Tumor to Kidney Ratios
摘要： ImmunoPET agents are being investigated to assess the status of epidermal growth factor receptor 2 (HER2) in breast cancer patients with the goal of selecting those likely to benefit from HER2-targeted therapies and monitoring their progress after these treatments. We have been exploring the use of single domain antibody fragments (sdAbs) labeled with 18F using residualizing prosthetic agents for this purpose. In this study, we have labeled two sdAbs that bind to different domains on the HER2 receptor — 2Rs15d and 5F7 — using 2,3,5,6-tetrafluorophenyl 6-[18F]fluoronicotinate ([18F]TFPFN) and evaluated their HER2 targeting properties in vitro and in vivo. The overall decay-corrected radiochemical yield for the synthesis of [18F]TFPFN-2Rs15d and [18F]TFPFN-5F7 was 5.7 ± 3.6% and 4.0 ± 2.0%, respectively. Radiochemical purity of labeled sdAbs was >95%; immunoreactive fractions were about 60% and affinity was in the low nanomolar range. Intracellularly trapped activity from [18F]TFPFN-2Rs15d and [18F]TFPFN-5F7 in HER2-expressing SKOV-3 ovarian and BT474M1 breast carcinoma cells were similar to the sdAbs labeled using the previously validated radioiodination residualizing prosthetic agents N-succinimidyl 4-guanidinomethyl-3-[125I]iodobenzoate ([125I]SGMIB) and N-succinimidyl 3-guanidinomethyl-5-[125I]iodobenzoate (iso-[125I]SGMIB). Intracellular activity was about 2-fold higher for radiolabeled 5F7 compared with 2Rs15d for both 18F and 125I. While tumor uptake of both [18F]TFPFN-2Rs15d and [18F]TFPFN-5F7 was comparable to those for the co-administered 125I-labeled sdAb, renal uptake of the 18F-labeled sdAbs was substantially lower. In microPET images, tumor was clearly delineated in SKOV-3 and BT474 xenograft-bearing athymic mice with low levels of background activity in normal tissues except bladder. These results indicate that the [18F]TFPFN prosthetic group could be a valuable reagent for developing sdAb-based immunoPET imaging agents.
关键词： N-Succinimidyl 4-fluorobenzoate (SFB),2,3,5,6-etrafluorophenyl 6-fluoronicotinate (TFPFN),single domain antibody fragment,immunoPET,fluorine-18,HER2
更新于2025-09-11 14:15:04
-
2-(4-Methylsulfonylphenyl)pyrimidines as Prospective Radioligands for Imaging Cyclooxygenase-2 with PET—Synthesis, Triage, and Radiolabeling
摘要： Cyclooxygenase 2 (COX-2) is an inducible enzyme responsible for the conversion of arachidonic acid into the prostaglandins, PGG2 and PGH2. Expression of this enzyme increases in inflammation. Therefore, the development of probes for imaging COX-2 with positron emission tomography (PET) has gained interest because they could be useful for the study of inflammation in vivo, and for aiding anti-inflammatory drug development targeting COX-2. Nonetheless, effective PET radioligands are still lacking. We synthesized eleven COX-2 inhibitors based on a 2(4-methylsulfonylphenyl)pyrimidine core from which we selected three as prospective PET radioligands based on desirable factors, such as high inhibitory potency for COX-2, very low inhibitory potency for COX-1, moderate lipophilicity, and amenability to labeling with a positron-emitter. These inhibitors, namely 6-methoxy-2-(4-(methylsulfonyl)phenyl-N-(thiophen-2ylmethyl)pyrimidin-4-amine (17), the 6-fluoromethyl analogue (20), and the 6-(2-fluoroethoxy) analogue (27), were labeled in useful yields and with high molar activities by treating the 6-hydroxy analogue (26) with [11C]iodomethane, [18F]2-fluorobromoethane, and [d2-18F]fluorobromomethane, respectively. [11C]17, [18F]20, and [d2-18F]27 were readily purified with HPLC and formulated for intravenous injection. These methods allow these radioligands to be produced for comparative evaluation as PET radioligands for measuring COX-2 in healthy rhesus monkey and for assessing their abilities to detect inflammation.
关键词： fluorine-18,COX-2,carbon-11,radioligand
更新于2025-09-09 09:28:46