Anne Roivainen

• PhD, Professor of Preclinical Imaging and Drug Research
• Professor (Full) at University of Turku

Background The macrophage mannose receptor (CD206) is expressed predominantly on the surface of M2-type macrophages, which play a role in resolution of inflammation after myocardial injury. The purpose of this study was to evaluate the utility of CD206-targeted PET tracer Al[¹⁸F]F-NOTA-D10CM, a fluorinated mannosylated dextran derivative, for imagi...

Prior studies reveal seasonal variations of mu-opioid receptor (MOR) signaling in both the brain and the brown adipose tissue (BAT). However, the potential seasonality effect on brain-BAT interactions, related to this signaling pathway, remains unknown. Understanding this dynamic seasonal rhythm may provide novel insights into seasonal affective ch...

Folate receptors (FRs), membrane-bound proteins that bind specifically to folate with high affinity, are overexpressed by various cancer types and are therefore used as targets for delivery of therapeutic agents. Molecular spherical nucleic acids (MSNAs) are dendritic formulations of oligonucleotides (ONs) that may have advantages over linear paren...

Backgrounds Myocardial work (MW) indices are new echocardiography parameters of left ventricular (LV) performance that consider afterload and global longitudinal strain analysis. However, the relationships between MW indices, myocardial perfusion and viability remain unclear after acute myocardial infarction (AMI). Aims To evaluate relationships b...

Backgrounds The myocardial work indices (MW indices) are novel echocardiographic parameters that quantify myocardial deformation and concomitant left ventricular pressure. However, there is little current data on trajectories and determinants of MW indices after acute myocardial infarction (AMI). Purpose We aimed to evaluate the trajectories of my...

Introduction Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear. Objectives This study investigated ET-ind...

In this study, we investigated the impact of bariatric surgery on the adipose proteome to better understand the metabolic and cellular mechanisms underlying weight loss following the procedure. A total of 46 patients with severe obesity were included, with samples collected both before and after bariatric surgery. Additionally, 15 healthy, non-obes...

Background Expression of folate receptor-β (FR-β) on the activated macrophages is associated with inflammatory diseases. However, the role of FR-β in the immune response following myocardial infarction (MI) remains unknown. Purpose To investigate FR-β-targeted positron emission tomography (PET) tracer aluminium fluoride-18-labeled 1,4,7,-triazacyl...

Context Increased standing time has been associated with improved health, but the underlying mechanism is unclear. Objectives We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities. Methods In this single-center clinical trial with randomized...

Purpose Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) is increasingly used in FUO and IUO, but the o...

Purpose Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[¹⁸F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer’s ability to target the macrophage mannose receptor CD206. Methods First, the uptake of intravenously (i....

Background Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (¹⁸...

Inflammatory bowel disease (IBD) can be imaged with positron emission tomography (PET), but existing PET radiopharmaceuticals have limited diagnostic accuracy. Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1...

Pretargeted concept in positron emission tomography (PET) together with bioorthogonal chemistry is an elegant solution to study processes with slow pharmacokinetics by utilizing radiotracers labeled with short-lived radionuclides. Namely, radiotracers based on tetrazine ligation with trans-cyclooctene (TCO) via the inverse electron demand Diels–Ald...

[68Ga]Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvβ3 integrin, which is upregulated during angiogenesis soon after acute myocardial infarction (AMI). We prospectively evaluated determinants of myocardial uptake of [68Ga]Ga-NODAGA-RGD and its associations with left ventricular (LV) function in patients after AMI. Methods: Myocardial bloo...

MicroRNAs (miRNAs) are a class of regulatory non-coding RNAs that finetune cellular functions by modulating the stability and abundance of their target mRNAs, thereby contributing to regulation of tissue homeostasis. MiRNA genes are transcribed similarly to protein-coding genes and recent studies have enabled their annotation and quantification gen...

Background Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ ⁶⁸ Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer ta...

18F-Labeled [60]fullerene-based molecular spherical nucleic acids (MSNAs), consisting of a human epidermal growth factor receptor 2 (HER2) mRNA antisense oligonucleotide sequence with a native phosphodiester and phosphorothioate backbone, were synthesized, site-specifically labeled with a positron emitting fluorine-18 and intravenously administrate...

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a s...

Introduction Non-invasive imaging techniques such as positron emission tomography (PET) are extremely important for cancer detection and characterization especially for difficult to biopsy or extremely delicate organs such as the brain. The folate analogue 1,4,7-triazacylononane-1,4,7-triacetic acid-conjugated folate radiolabeled with aluminum fluo...

Purpose: In addition to being expressed on liver sinusoidal endothelial cells, mannose receptors are also found on antigen-presenting cells, including macrophages, which are mainly involved in the inflammation process. Dextran derivatives of various sizes containing cysteine and mannose moieties have previously been labeled with 99mTc and used for...

Coronary artery disease (CAD) is a pandemic disease where up to half of the risk is explained by genetic factors. Advanced insights into the genetic basis of CAD require deeper understanding of the contributions of different cell types, molecular pathways, and genes to disease heritability. Here, we investigate the biological diversity of atheroscl...

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-...

Introduction Mannose receptor (CD206) is primarily expressed on the surface of alternatively activated macrophages that are involved in resolution of inflammation after myocardial injury [1]. The purpose of this study was to evaluate mannose receptor targeting positron emission tomography (PET) tracer Al[18F]F-NOTA-DCM consisting of dextran backbon...

Background Congenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but i...

Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its...

Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signa...

Molecular imaging offers various radiopharmaceuticals for the infection imaging, such as antimicrobial peptides, leukocytes, cytokines, antibiotics, sugars and so on. They present both advantages and disadvantages, however none of them are proved to be highly specific for bacteria. Various factors, including the number and strain of bacteria, the i...

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...

Coronary artery disease (CAD) is a pandemic disease where up to half of the risk is explained by genetic factors. Advanced insights into genetic basis of CAD require deeper understanding of the contributions of different cell types, molecular pathways and genes to disease heritability. Here, we investigate the biological diversity of atherosclerosi...

Radiolabeled peptides have emerged as highly specific agents for targeting receptors expressed in tumors for therapeutic and diagnostic purposes. Peptides developed for positron emission tomography (PET) are typically radiolabeled using prosthetic groups or bifunctional chelators for fast "kit-like" incorporation of the radionuclide into the struct...

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Academy of Finland Sigrid Jusélius Foundation Adipose tissue influences the physiological and pathological processes in our body by regulating lipid storage and metabolic homeostasis. Extracellular matrix (ECM) is a dynamic and complex assemblage consisting of pol...

[This corrects the article DOI: 10.3389/fimmu.2022.821423.].

Photoperiod drives metabolic activity of brown adipose tissue (BAT), and affects food intake and weight gain in mammals. Sympathetic innervation in BAT controls thermogenesis and facilitates physiological adaption to seasons, but the exact mechanism remains elusive. Previous studies show that the central opioid signaling tunes BAT heating and the b...

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...

Positron emission tomography (PET) is a quantitative imaging technique that uses molecules labeled with positron-emitting radionuclides to visualize and measure biochemical processes in the tissues of living subjects. In recent years, different PET tracers have been evaluated for their ability to characterize the atherosclerotic process in order to...

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...

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...

Purpose The three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[¹⁸F]Fluoroglutamine ([¹⁸F]FGln), L-[methyl-¹¹C]Methionine ([¹¹C]Met), and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for...

Brown adipose tissue (BAT) expresses uncoupling protein-1 (UCP1), which enables energy to be exerted towards needed thermogenesis. Beige adipocytes are precursor cells interspersed among white adipose tissue (WAT) that possess similar UCP1 activity and capacity for thermogenesis. The raccoon dog (Nyctereutes procyonoides) is a canid species that ut...

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...

Purpose To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer. Methods Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI...

An azide-functionalized 12-armed Buckminster fullerene has been monosubstituted in organic media with a substoichiometric amount of cyclooctyne-modified oligonucleotides. Exposing the intermediate products then to the same reaction (i.e., strain-promoted alkyne–azide cycloaddition, SPAAC) with an excess of slightly different oligonucleotide constit...

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...

Funding Acknowledgements Type of funding sources: None. Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) can detect arterial inflammation in individuals with atherosclerosis, but the associations among different vascular territories for 18F-FDG uptake are not known. Purpose We explored any possible correlation betwee...

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlie...

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...

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]...

Seasonal rhythms influence emotion and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we first conducted a cross-sectional study with previously acquired human [11C]carfentanil P...

Background We investigated the image quality of ¹¹C, ⁶⁸Ga, ¹⁸F and ⁸⁹Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was...

Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive‐like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing,...

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...

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...

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...

Background The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection.Methods and resultsThirty patients with suspected CIED...

Hydroxysteroid 17-beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b...

Seasonal rhythms influence mood and sociability. The mu-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but seasonal variation in the MOR system remains elusive. We used positron emission tomography (PET) imaging with [11C]carfentanil, a high affinity MOR radioligand, to repeatedly measure in vivo...

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...

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...

Background and aims Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[¹⁸F]-fluoro-d-glucose (¹⁸F-FDG), a positron emission tomography tracer of inflammation, in a...

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of ¹⁸F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translat...

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...

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...

Background: [⁶⁸Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [⁶⁸Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infec...

Mitochondrial dysfunction elicits stress responses that safeguard cellular homeostasis against metabolic insults. Mitochondrial integrated stress response (ISRmt) is a major response to mitochondrial (mt)DNA expression stress (mtDNA maintenance, translation defects), but the knowledge of dynamics or interdependence of components is lacking. We repo...

18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis...

Background Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). Methods and results...