Profile
Description of Research
Timely identification and localization of inflammatory foci are critical for adequate treatment of patients and the 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 vessels 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
Andriana P, Fair-Mäkelä R, Palani S, Liljenbäck H, Kärnä S, Iqbal I, Makrypidi K, Suni A, Rajander J, Pirmettis I, Li X-G, Jalkanen S, Saraste A, Salmi M, Roivainen A. Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice. Eur J Nucl Med Mol Imaging 51:2216-2228, 2024
Bhowmik AA, Heikkilä TRH, Polari L, Virta J, Liljenbäck H, Moisio O, Li X-G, Viitanen R, Jalkanen S, Koffert J, Toivola DM, Roivainen A. Detection of intestinal inflammation by vascular adhesion protein-1-targeted positron emission tomography in murine models of colitis. Mol Imaging Biol 26:322–333, 2024
Jahandideh A, Virta J, Li X-G, Liljenbäck H, Moisio O, Ponkamo J, Rajala N, Alix M, Lehtonen J, Mäyränpää MI, Salminen TA, Knuuti J, Jalkanen S, Saraste A, Roivainen A. Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis. J Nucl Cardiol 30:2760-2772, 2023
Miner MWG, Liljenbäck H, Virta J, Kärnä S, Viitanen R, Elo P, Gardberg M, Teuho J, Saipa P, Rajander J, Mansour A Mansour H, Cleveland NA, Low PS, Li X-G, Roivainen A. High folate receptor expression in gliomas can be detected in vivo using folate-based positron emission tomography with high tumor-to-brain uptake ratio divulging potential future targeting possibilities. Front Immunol 14:1145473, 2023
Moisio O, Virta J, Yatkin E, Liljenbäck H, Palani S, Viitanen R, Miner MWG, Oikonen V, Tolvanen T, Vugts DJ, Taimen P, Li X-G, Holmén M, Jalkanen S, Roivainen A. Preclinical evaluation of a humanized antibody against common lymphatic endothelial and vascular endothelial receptor-1, 89Zr-desferrioxamine-bexmarilimab, in a rabbit model of renal fibrosis. J Nucl Med 64:555-560, 2023
Sun L, Aarnio R, Atencio Herre E, Kärnä S, Palani S, Virtanen H, Liljenbäck H, Virta J, Honkaniemi A, Oikonen V, Han C, Laurila S, Bucci M, Helin S, Yatkin E, Nummenmaa L, Nuutila P, Tang J, Roivainen A. [11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue. Eur J Nucl Med Mol Imaging 50:266-274, 2023
Viitanen R, Virtanen H, Liljenbäck H, Moisio O, Li X-G, Nicolini V, Richard M, Klein C, Nayak T, Jalkanen S, Roivainen A. [68Ga]Ga-DOTA-Siglec-9 detects pharmacodynamic changes of FAP-targeted IL2 variant immunotherapy in B16-FAP melanoma mice. Front Immunol 13:901693, 2022
Palani S, Miner MWG, Virta J, Liljenbäck H, Eskola O, Örd T, Ravindran A, Kaikkonen MU, Knuuti J, Li X-G, Saraste A, Roivainen A. Exploiting glutamine consumption in atherosclerotic lesions by positron emission tracer (2S, 4R)-4-18F-fluoroglutamine. Front Immunol 13:821423, 2022
Ståhle M, Hellberg S, Virta J, Liljenbäck H, Metsälä O, Jauhiainen M, Saukko P, Ylä-Herttuala S, Nuutila P, Knuuti J, Saraste A, Roivainen A. Evaluation of glucagon-like peptide-1 receptor expression in nondiabetic and diabetic atherosclerotic mice using PET tracer 68Ga-NODAGA-exendin-4. Am J Physiol Endocrinol Metab 320:E989–E998, 2021
Elo P, Li X-G, Liljenbäck H, Gardberg M, Moisio O, Miner M, Virta J, Saraste A, Srinivasarao M, Pugh M, Low PS, Knuuti J, Jalkanen S, Airas L, Lu YJ, Roivainen A. Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis. J Neuroinflammation 18:30, 2021