In vivo Imaging of Inflammation

Organization

Turku PET Centre, University of Turku and Turku University Hospital

Research group:

Senior Scientists: Ass. Prof. Saraste Antti, MD, PhD; Adj. Prof. Xiang-Guo Li, PhD

Post-Docs: Virtanen Helena, PhD

Graduate students: Elo Petri, MSc; Grönman Maria, MSc; Kiugel Max, MSc, BM; Kyläinpää Ella, MSc; Käkelä Meeri, MSc; Liljenbäck Heidi, MSc; Luoto Pauliina, MSc; Moisio Olli, MSc; Mäkilä Jussi, MSc, BM; Siitonen Riikka, MSc; Ståhle Mia, MSc; Uotila Sauli, MD; Virta Jenni, MSc

Undergraduate students: Miner Maxwell, BSc; Riehakainen Leon, BSc

The goal of the project:

Timely identification and localization of inflammatory foci are critical for adequate treatment of patients and current methodology is not sufficient to meet this goal. Inflammation is a significant component of several chronic diseases involving the cardiovascular, metabolic, respiratory, gastro-intestinal, musculoskeletal and nervous systems. Positron emission tomography (PET) with targeted probes enables evaluation of the molecular and cellular pathophysiological mechanisms of diseases (i.e. molecular imaging). However, more specific markers than the currently used glucose analogue, fluorodeoxyglucose 18F-FDG, are needed to assess inflammation and its consequences in different pathologies. Aims of the present study are pre-clinical evaluation of new targeted probes and techniques for molecular imaging of inflammation. Based on previous success, our main target is vascular adhesion protein 1 (VAP-1) that mediates leukocyte traffic into inflamed site(s) and assessment of its elevated expression in inflammation states. The imaging agents will be evaluated in experimental models of inflammation, in healthy subjects and in patients. VAP-1 is abundantly expressed e.g. in synovial blood vessel in rheumatoid arthritis joints. The main hypothesis is that sensitive whole-body imaging of inflammation will enable early diagnosis, help in patient selection to particular therapy and monitor therapy outcome. Noteworthy, the development of new radiopharmaceuticals requires several years’ effort and expensive proof-of-concept and acute toxicity studies. This project mainly focuses on PET tracers and to lesser extent magnetic resonance (MR) and single-photon emission computed tomography (SPECT) imaging agents.

Representative publications:

Silvola JMU, Virtanen H, Siitonen R, Hellberg S, Liljenbäck H, Metsälä O, Ståhle M, Saanijoki T, Käkelä M, Hakovirta H, Ylä-Herttuala S, Saukko P, Jauhiainen M, Veres TZ, Jalkanen S, Knuuti J, Saraste A, Roivainen A. Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques. Sci Rep 6:35089, 2016

Haavisto M, Saraste A, Pirilä L, Hannukainen JC, Kalliokoski KK, Kirjavainen A, Kemppainen J, Möttönen T, Knuuti J, Yli-Kerttula T, Roivainen A. Influence of triple disease modifying anti-rheumatic drug therapy on carotid artery inflammation in drug-naive patients with recent onset of rheumatoid arthritis. Rheumatol 55:1777-1785, 2016

Virtanen H, Autio A, Siitonen R, Liljenbäck H, Saanijoki T, Lankinen P, Mäkilä J, Käkelä M, Teuho J, Savisto N, Jaakkola K, Jalkanen S, Roivainen A. 68Ga-DOTA-Siglec-9 – a new imaging tool to detect synovitis. Arthritis Res Ther 17:308, 2015

Autio A, Vainio PJ, Suilamo S, Mali A, Vainio J, Saanijoki T, Noponen T, Ahtinen H, Luoto P, Teräs M, Jalkanen S, Roivainen A. Preclinical evaluation of a radioiodinated fully human antibody for in vivo imaging of vascular adhesion protein-1-positive vasculature in inflammation. J Nucl Med 54:1315–1319, 2013

Aalto K, Autio A, Kiss EA, Elima K, Nymalm Y, Veres TZ, Marttila-Ichihara F, Elovaara H, Saanijoki T, Crocker PR, Maksimow M, Bligt E, Salminen TA, Salmi M, Roivainen A, Jalkanen S. Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be utilized in PET-imaging of inflammation and cancer. Blood 118:3725–3733, 2011

Principal Investigator
Anne Roivainen, PhD,
Professor of Preclinical Imaging and Drug Research
  • VAP-1 targeting probes
  • 68Ga PET ligands
  • Multimodal imaging