18F RGD

Integrin αv β3 receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine-glycine-aspartatic acid (RGD) peptide and integrin αv β3 , but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of (18)F. In this study, the dimeric RGD peptide, E-[c(RGDfK)]2, was conjugated with NODAGA and radiolabeled with (18)F in a simple one-pot process with a radiolabeling yield of 20%, the whole process lasting only 45 min...

Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [(18)F]-fluoride into BODIPY dyes...

18F positron emission tomography (PET) has a number of attributes that make it clinically attractive, including nearly 100% positron efficiency, very high specific radioactivity, and a short half-life of ≈ 110 minutes. However, the short half-life of 18F and the poor nucleophilicity of fluoride introduce challenges for the incorporation of 18F into complex molecules. Recently, the tetrazine-trans-cyclooctene ligation was introduced as a novel 18F labeling method that proceeds with fast reaction rates without catalysis...

Breast cancer is a heterogenetic tumor at the cellular level with multiple factors and components. The inconsistent expression of molecular markers during disease progression reduces the accuracy of diagnosis and efficacy of target-specific therapy. Single target-specific imaging agents can only provide limited tumor information at one time point. In contrast, multiple target-specific imaging agents can increase the accuracy of diagnosis. The aim of this study was to demonstrate the ability of multi-agent imaging to discriminate such differences in single tumor...

With favorable pharmacokinetics and binding affinity for α(v)β(3) integrin, (18)F-labeled dimeric cyclic RGD peptide ([(18)F]FPPRGD2) has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18)F-fluoride-aluminum complex labeled RGD tracer ([(18)F]AlF-NOTA-PRGD2), provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68)Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(v)β(3)...

BACKGROUND: Expression of α(v)β(3) integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of α(v)β(3) integrin-targeted positron emission tomography tracer (18)F-galacto-RGD in mouse atherosclerotic plaques. METHODS AND RESULTS: Hypercholesterolemic LDLR(-/-) ApoB(100/100) mice on high-fat diet for 4 months were randomized to further 3 months on high-fat diet (high-fat group, n = 8) or regular mouse chow (intervention group, n = 7)...

UNLABELLED: 2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4-(3-(18)F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid ((18)F-RGD-K5) has been developed as an α(v)β(3) integrin marker for PET. The purpose of this study was to determine the biodistribution and estimate the radiation dose from (18)F-RGD-K5 using whole-body PET/CT scans in monkeys and humans...

PURPOSE: Non-invasive PET imaging with radiolabeled RGD peptides for α(v)β(3) integrin targeting has become an important tool for tumor diagnosis and treatment monitoring in both pre-clinical and clinical studies. To better understand the molecular process and tracer pharmacokinetics, we introduced kinetic modeling in the investigation of (18)F-labeled RGD peptide monomer (18)F-FP-c(RGDyK) (denoted as (18)F-FPRGD) and dimer (18)F-FP-PEG3-E[c(RGDyK)](2) (denoted as (18)F-FPPRGD2). PROCEDURES: MDA-MB-435 tumor-bearing mice underwent 60 min dynamic PET scans following the injection of either (18)F-FPRGD or (18)F-FPPRGD2...

PURPOSE: The α(v)β(3) integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin α(v)β(3)-targeting positron emission tomography (PET) probe, (18)F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model. METHODS: Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion...

[(18)F]FPPRGD2, an F-18 labeled dimeric cyclic RGDyK peptide, has favorable properties for PET imaging of angiogenesis by targeting the α(v)β(3) integrin receptor. This radiotracer has been approved by the FDA for use in clinical trials. However, the time-consuming multiple-step synthetic procedure required for its preparation may hinder the widespread usage of this tracer. The recent development of a method using an F-18 fluoride-aluminum complex to radiolabel peptides provides a strategy for simplifying the labeling procedure...

PURPOSE: A reliable and routine process to introduce a new ¹⁸F-labeled dimeric RGD-peptide tracer ([¹⁸F]FPP(RGD₂) for noninvasive imaging of α(v)β₃ expression in tumors needed to be developed so the tracer could be evaluated for the first time in man. Clinical-grade [¹⁸F]FPP(RGD)₂ was screened in mouse prior to our first pilot study in human. PROCEDURES: [¹⁸F]FPP(RGD)₂ was synthesized by coupling 4-nitrophenyl-2-[¹⁸F]fluoropropionate ([¹⁸F]NPE) with the dimeric RGD-peptide (PEG₃-c(RGDyK)₂)...

UNLABELLED: Arginine-glycine-aspartate (RGD)-binding α(V)β(3)-integrin and α(V)β(5)-integrin play key roles in tumor angiogenesis. We examined an (18)F-labeled small peptide (fluciclatide [United States Adopted Name (ASAN)-approved, International Nonproprietary Name (INN)-proposed name], previously referred to as AH111585) containing an RGD sequence. Fluciclatide binds with a high (nM) affinity to α(V)β(3)-integrin and α(V)β(5)-integrin, which are highly expressed on tumors and the tumor neovasculature...

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab™, GE Healthcare). PROCEDURES: Two synthesis approaches were implemented on this module: the classical "two-pot radiosynthesis" and the more recently described "one-pot" method. RESULTS: The "two-pot" approach affords [(18)F]SFB with a 42% decay-corrected yield in 57 min (n = 24) with a chemical purity sufficient to avoid an intermediate HPLC purification...

A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425-432, 2009). Although (18)F-labeled heterodimers showed significantly better microPET imaging quality than (18)F-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin αvβ3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications...

PURPOSE: We assessed whether imaging α(v)β(3) integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. METHODS: Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles)...

PURPOSE: In vivo imaging of α(v)β(3) has important diagnostic and therapeutic applications. (18)F-Galacto-arginine-glycine-aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin α(v)β(3) expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin α(v)β(3)-binding affinity due to the polyvalency effect. Here, we compared a number of new dimeric RGD peptide tracers with the clinically used (18)F-galacto-RGD...

BACKGROUND: (18)F-Galacto-RGD is a positron emission tomography (PET) tracer binding to alpha(v)beta(3) integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated (18)F-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose. METHODS AND RESULTS: Hypercholesterolemic LDLR(-/-)ApoB(100/100) mice on a Western diet and normally fed adult C57BL/6 control mice were injected with (18)F-galacto-RGD and (3)H-deoxyglucose followed by imaging with a small animal PET/CT scanner...

Integrin alpha(v)beta(3) plays a significant role in tumor angiogenesis and is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic (RGD) tripeptide sequence. These include vitronectin, fibronectin, fibrinogen, lamin, collagen, Von Willibrand's factor, osteoponin, and adenovirus particles. Integrin alpha(v)beta(3) is expressed at low levels on epithelial cells and mature endothelial cells, but it is overexpressed on the activated endothelial cells of tumor neovasculature and some tumor cells...

PURPOSE: To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate alpha(v)beta(3) from alpha(v)beta(5) integrin, thus allowing the in vivo selective visualization of alpha(v)beta(3) expression by single-photon and positron emission tomography (PET) imaging. EXPERIMENTAL DESIGN: The chimeric peptide was preliminarily tested for inhibition of alpha(v)beta(3)-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing alpha(v)beta(3) (Kalpha(v)beta(3)) or alpha(v)beta(5) (Kalpha(v)beta(5)) integrin...

Inhibitors targeting the integrin alpha(v)beta(3) are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate (18)F-labeled glycosylated Arg-Gly-Asp peptide ([(18)F]Galacto-RGD) PET for noninvasive imaging of alpha(v)beta(3) expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [(18)F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis...