Xiang-Guo Li

Xiang-Guo Li
University of Turku | UTU · Turku PET Centre, Radiopharmaceutical Chemistry Laboratory

Assistant Professor in Radiochemistry PhD
Radiochemistry research and new radiopharmaceutical development

About

78
Publications
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759
Citations
Citations since 2017
45 Research Items
455 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120

Publications

Publications (78)
Article
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Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1), and is in clinical trials for macrophage-guided cancer immunotherapy. In addition to cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated 89Zr-...
Article
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Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity ag...
Article
68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers...
Article
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Increased glutamine metabolism by macrophages is associated with development of atherosclerotic lesions. Positron emission tomography/computed tomography (PET/CT) with a glutamine analog (2S,4R)-4-18F-fluoroglutamine (18F-FGln) allows quantification of glutamine consumption in vivo. Here, we investigated uptake of 18F-FGln by atherosclerotic lesion...
Article
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The ⁶⁸ Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([ ⁶⁸ Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α v β 3 integrin that is upregulated during angiogenesis and inflammation. We studied whether α v β 3...
Article
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Purpose The three positron emission tomography (PET) imaging compounds: (2 S ,4 R )-4-[ ¹⁸ F]Fluoroglutamine ([ ¹⁸ F]FGln), L -[methyl- ¹¹ C]Methionine ([ ¹¹ C]Met), and 2-deoxy-2-[ ¹⁸ F]fluoro- D -glucose ([ ¹⁸ F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging system...
Article
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Radiolabeled RGD peptides targeting expression of αvβ3 integrin have been applied to in vivo imaging of angiogenesis. However, there is a need for more information on the quantitative relationships between RGD peptide uptake and the dynamics of angiogenesis. In this study, we sought to measure the binding of [68Ga]NODAGA-RGDyK to αvβ3 integrin in a...
Article
Cardiovascular effects of glucagon-like peptide-1 receptor (GLP-1R) agonist therapies are potentially mediated by anti-inflammatory effects on atherosclerosis. Our study demonstrates that ⁶⁸ Ga-NODAGA-exendin-4, a radioligand specifically targeting GLP-1R, detects GLP-1R expression in inflamed atherosclerotic lesions in nondiabetic and diabetic hyp...
Article
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Background Activated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-β (FR-β), representing a promising target for the treatment of MS. Here, we both evaluated the efficacy of a novel folate-aminopterin construct (EC2319) in a rat focal model of multiple sclerosis (MS) and investigated the utility of ⁶⁸Ga-la...
Chapter
The early identification and localization of inflammation and infection is crucial for patient care, and positron emission tomography (PET) imaging provides a sensitive and quantitative tool for diagnosing and monitoring treatment efficacy. However, radiopharmaceuticals with better specificity than the currently used glucose analog, 2-Deoxy-2-[¹⁸F]...
Article
Full-text available
Sialic acid–binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A 68Ga-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharma...
Article
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Folate receptor β (FR-β), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. In...
Article
Full-text available
Folate receptor β (FR-β), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. In...
Preprint
Full-text available
Folate receptor β (FR-β) is one of the markers expressed on macrophages and a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [ ⁶⁸ Ga]Ga-NOTA-folate ( ⁶⁸ Ga-FOL). First, we determined the affinity of ⁶⁸ Ga-FOL using human FR-β expressing cells. Then, we studied atherosclerotic mice with...
Article
Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid conjugated folate (18F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macro...
Article
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Purpose The glutamine analogue (2S, 4R)-4-[¹⁸F]fluoroglutamine ([¹⁸F]FGln) was investigated to further characterize its pharmacokinetics and acquire in vivo positron emission tomography (PET) images of separate orthotopic and subcutaneous glioma xenografts in mice. Procedures [¹⁸F]FGln was synthesized at a high radiochemical purity as analyzed by...
Article
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Background: Folate receptor-β (FR-β) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-β expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced a...
Article
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The peptide-based radioactive compound [68Ga]Ga-DOTA-Siglec-9 is a novel agent for imaging of inflammation with positron emission tomography. The drug target of [68Ga]Ga-DOTA-Siglec-9 is vascular adhesion protein 1. Previous studies have obtained promising results with [68Ga]Ga-DOTA-Siglec-9 in experimental animals. However, before taking this nove...
Article
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Muscimol, the major psychoactive ingredient in the mushroom Amanita muscaria, has been regarded as a universal non‐selective GABA‐site agonist. Deletion of the GABAA receptor (GABAAR) δ subunit in mice (δKO) leads to a drastic reduction in high‐affinity muscimol binding in brain sections and to a lower behavioral sensitivity to muscimol than their...
Article
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Background Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling protects against cardiac dysfunction and remodeling after myocardial infarction (MI). The aim of the study was to evaluate ⁶⁸Ga-NODAGA-exendin-4 positron emission tomography (PET) for assessment of GLP-1R expression after MI in rats. Methods and Results Rats were studied...
Article
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Background: The expression of matrix metalloproteinases 2/9 (MMP-2/9) has been implicated in arterial remodeling and inflammation in atherosclerosis. We evaluated a gallium-68 labeled peptide for the detection of MMP-2/9 in atherosclerotic mouse aorta. Methods: We studied sixteen low-density lipoprotein receptor deficient mice (LDLR-/-ApoB100/100)...
Article
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Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor β (FR-β) is selectively expressed on macrophages, an FR targeted imaging agent could be useful for assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triace...
Article
Full-text available
We finally managed to establish a protocol for generating Good Manufacturing Practice (GMP)-grade gallium-68-labelled 1,4,7,0-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated sialic acidbinding immunoglobulin-like lectin 9 motif containing peptide ([68Ga]Ga-DOTA-Siglec-9), the first radiopharmaceutical for positron emission tomography ima...
Article
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Amino acid residues 283-297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1). VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation...
Article
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Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA-and 18F-fluorodeoxyribose-(FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle...
Article
Background Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated 68Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat. Methods Rats were injected with 43 ± 7.7 MBq of 68Ga-DOTA-peptide targeting MM...
Article
Background Radioligands of 18-kDa translocator protein (TSPO) expressed on activated macrophages are a potential approach for imaging of inflammation in atherosclerosis. We evaluated a novel TSPO-targeted tracer 18F-FEMPA for the detection of atherosclerotic plaque inflammation in mice. Methods and results The distribution kinetics of 18F-FEMPA was...
Article
Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 (18F) and study the 18F-labeled mannan in vitro and in vivo with positron emi...
Article
A new (18)F-labeled tetrazine derivative was developed aiming at optimal radiochemistry, fast reaction kinetics in inverse electron-demand Diels-Alder cycloaddition (IEDDA), and favorable pharmacokinetics for in vivo bioorthogonal chemistry. The radiolabeling of the tetrazine was achieved in high yield, purity, and specific activity under mild reac...
Article
Introduction:Macrophages are a major cell type in inflamed atherosclerotic plaques. Since folate receptor β (FR-β) is highly expressed in activated macrophages, we hypothesized that it might serve as a new marker for inflamed atherosclerotic plaques. Hypothesis: We aimed at evaluating a FR-β targeted PET tracer, Al ¹⁸ F NOTA-Folate, for the detecti...
Article
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Rupture-prone atherosclerotic plaques are characterized by accumulation of macrophages, which have shown to express somatostatin type 2 receptors. We aimed to investigate whether somatostatin receptor-targeting positron emission tomography (PET) tracers, [(68)Ga]DOTANOC, [(18)F]FDR-NOC, and [(68)Ga]DOTATATE, can detect inflamed atherosclerotic plaq...
Article
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A bicyclononyne-based prosthetic group has been developed for 18F-labeling of anti-microRNA-21, an oligonucleotide, in a near-stoichiometric manner.
Article
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Unlabelled: Somatostatin receptor subtype 2 (sstr2) is regarded as a potential target in malignant gliomas for new therapeutic approaches. Therefore, visualizing and quantifying tumor sstr2 expression in vivo would be highly relevant for the future development of sstr2-targeted therapies. The purpose of this study was to evaluate sstr2 status in e...
Article
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So far seven peptide-based (18)F-radiopharmaceuticals for diagnostic applications with positron emission tomography (PET) have entered into clinical trials. Three candidates out of these seven are glycosylated peptides, which may be explained by the beneficial influence of glycosylation on in vivo pharmacokinetics of peptide tracers. This protocol...
Article
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Peptide glycosylation with 5-deoxy-5-[(18)F]fluororibose was translated into preclinical settings. The novel (18)F-labeled Siglec-9 peptide was produced using an automated synthesis procedure. The (18)F-labeled Siglec-9 peptide showed favorable binding in the animal model of inflammation in vivo.
Article
Positron emission tomography (PET) is a powerful technology for medical and biological imaging and the scope of PET applications is expanding rapidly. The development of suitable PET tracers is at a central position in PET technology. An increasing number of peptides and proteins have been developed for the clinic due to their special properties wh...
Article
Taking advantage of the catalytic promiscuity of pyrimidine-catabolism enzymes (dihydropyrimidinase (E.C. 3.5.2.2), N-carbamoyl-β-alanine amidohydrolase (E.C. 3.5.1.6)), the production of different β-alanine derivatives starting from 5- and 6-monosubstituted dihydrouracils has been evaluated using a mimesis approach. In this work, the S-enantiosele...
Article
[(18)F]-5-Fluoro-5-deoxyribose ([(18)F]-FDR) conjugates much more rapidly than [(18)F]-FDG under mild reaction conditions to peptides and offers new prospects for mild and rapid bioconjugation for fluorine-18 labelling in PET imaging.
Article
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Kinetic resolution of three cyclic quaternary ethyl 1-amino-2,3-dihydro-1H-indene-1-carboxylates and both 1- and 2-amino-1,2,3,4-tetrahydronaphthalene analogues have been studied. Interesterification with butyl butanoate and Candida antarctica lipase B accomplished the task. The enantiomers of all 1-amino analogues reacted with excellent enantiosel...
Article
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A novel preparation of sodium [(18)F]-fluoroacetate is described where 5'-[(18)F]-fluoro-5'-deoxyadenosine is generated by a fluorinase catalysed reaction of S-adenosyl-l-methionine (SAM) with no carrier added [(18)F]-fluoride and then oxidation to [(18)F]-fluoroacetate by a Kuhn-Roth oxidative degradation.
Article
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A new enzymatic synthesis of alpha,beta-dipeptides has been developed with particular focus on the preparation of camosine (beta-alanyl-alpha-histidine) and analogues. The lipase PS-D from Burkholderia cepacia has been used as a catalyst for the formation of the peptide bond starting from a beta-lactam and a protected alpha-amino acid. (C) 2009 Els...
Article
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The work describes fluorine-activated and N-Boc-activated β-lactams as acyl donors to N-nucleophiles in the presence of Burkholderia cepacia lipase (lipase PS-D). Fluorine activation at the β-lactam ring causes the ring to open in high enantioselectivity and allows the preparation of β-dipeptides and β-amino amides. In the case of N-Boc-activation,...
Article
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Both enantiomers of fluorinated and non-fluorinated 4-phenyl-2-azetidinones are prepared in high enantiopurities (ee 99%) by a chemoenzymatic method, using a double resolution technique to N-hydroxymethylated β-lactams in the presence of Burkholderia cepacia lipase as the source of enantiopurity. N-Deprotections yield the β-lactam enantiomers from...
Article
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This paper concentrates on studies of the acylation of alcohols with 3,3-difluoro-4-phenylazetidin-2-one rac-1, trans-3-fluoro-4-phenylazetidin-2-one rac-2 and 4-phenylazetidin-2-one rac-3 in the presence of immobilized lipase PS from Burkholderia cepacia in dry tert-butyl methyl ether (TBME). Fluorine activation in the compounds studied was essent...
Article
A number of beta-dipeptides were prepared by two-step lipase-catalyzed reactions where N-acetylated beta-amino esters were first activated as 2,2,2-trifluoroethyl esters with Candida antarctica lipase B (CAL-B). The activated esters were then used to acylate beta-amino ester in the presence of Candida antarctica lipase A (CAL-A) in dry Et2O or i-Pr...
Article
Full-text available
A simple chemoenzymatic method for the preparation of the enantiomers of 4-benzyl-β-lactam (4-benzylazetidin-2-one) from allylbenzene has been described. The enantiomers of this key intermediate have been used to produce the corresponding enantiomers of β-phenylalanine and N-Boc-protected β-phenylalanine amide through the simple cleavage of the lac...