Molekulare Entzündungsdiagnostik im 21. Jahrhundert – der Weg zu mehr Spezifität und individualisierter Medizin?

Zusammenfassung

Die Diagnostik entzündlicher Erkrankungen stellt nach wie vor eine große klinische Herausforderung dar. Die molekulare Bildgebung erlaubt die Darstellung eines entzündlichen Geschehens in vivo, wobei pathophysiologische Veränderungen in einer frühen Phase des Entzündungsprozesses noch vor dem Auftreten anatomischer Veränderungen detektierbar sind. Es stehen verschiedene nuklearmedizinische Tracer zur Entzündungsdiagnostik mittels Gammakamera und PET/CT mit unterschiedlicher Spezifität zur Darstellung einer Entzündung zur Verfügung.

Der vorliegende Artikel befasst sich schwerpunktmäßig mit den Entwicklungen der nuklearmedizinischen Entzündungsdiagnostik in den letzten 16 Jahren. Auf dem Weg zu mehr Spezifität und Individualität in der Bildgebung akuter und chronischer Entzündungen werden erste Ergebnisse über die klinische Anwendung neue Tracer, mit ihren jeweiligen Vorzügen und Limitationen, vorgestellt.

Abstract

Diagnosis of inflammatory diseases still displays a major clinical issue. Molecular imaging is able to identify infection and inflammation in an early stage before the occurrence of anatomical changes. A variety of radiolabeled tracers for imaging infection and inflammation has been developed for SPECT and PET imaging so far.

This article mainly reviews the development of diagnostics in acute and chronic inflammation in nuclear medicine within the last 16 years. It gives an overview of first clinical results of newly developed radiotracers and their advantages and limitations on the way to more specificity and individualized diagnostics.

Schlüsselwörter

Entzündung - PET/CT - SPECT - SPECT/CT - Tracer

Keywords

Infection - Inflammation - PET/CT - SPECT - Tracer

• Literatur

• 1 Aghanejad A, Jalilian AR, Ardaneh K. et al. Preparation and Quality Control of (68)Ga-Citrate for PET Applications. Asia Ocean J Nucl Med Biol 2015; 3: 99-106
• 2 Annovazzi A, Biancone L, Caviglia R. et al. 99mTc-interleukin-2 and (99m)Tc-HMPAO granulocyte scintigraphy in patients with inactive Crohn's disease. Eur J Nucl Med Mol Imaging 2003; 30: 374-382
• 3 Annovazzi A, Bonanno E, Arca M. et al. 99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques. Eur J Nucl Med Mol Imaging 2006; 33: 117-126
• 4 Aslam S, Darouiche RO. Prosthetic joint infections. Curr Infect Dis Rep 2012; 14: 551-557
• 5 Auletta S, Galli F, Lauri C. et al. Imaging bacteria with radiolabelled quinolones, cephalosporins and siderophores for imaging infection: a systematic review. Clin Transl Imaging 2016; 4: 229-252
• 6 Baldoni D, Waibel R, Blauenstein P. et al. Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model. Mol Imaging Biol 2015; 17: 829-837
• 7 Barrabes JA, Garcia-Dorado D, Mirabet M. et al. Antagonism of selectin function attenuates microvascular platelet deposition and platelet-mediated myocardial injury after transient ischemia. J Am Coll Cardiol 2005; 45: 293-299
• 8 Barrera P, van der Laken CJ, Boerman OC. et al. Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis. Rheumatology (Oxford) 2000; 39: 870-874
• 9 Bar-Shalom R, Yefremov N, Guralnik L. et al. SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of infection. J Nucl Med 2006; 47: 587-594
• 10 Becker W, Emmrich F, Horneff G. et al. Imaging rheumatoid arthritis specifically with technetium 99m CD4-specific (T-helper lymphocytes) antibodies. Eur J Nucl Med 1990; 17: 156-159
• 11 Beiki D, Yousefi G, Fallahi B. et al. (99m)tc-Ubiquicidin [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41], a Promising Radiopharmaceutical to Differentiate Orthopedic Implant Infections from Sterile Inflammation. Iran J Pharm Res 2013; 12: 347-353
• 12 Bennink RJ, Thurlings RM, van Hemert FJ. et al. Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in patients with rheumatoid arthritis. J Nucl Med 2008; 49: 1380-1385
• 13 Bevilacqua M, Butcher E, Furie B. et al. Selectins: a family of adhesion receptors. Cell 1991; 67: 233
• 14 Bhatt J, Mukherjee A, Korde A. et al. Radiolabeling and Preliminary Evaluation of Ga-68 Labeled NODAGA-Ubiquicidin Fragments for Prospective Infection Imaging. Mol Imaging Biol 2017; 19: 59-67
• 15 Bhattacharya A, Kochhar R, Sharma S. et al. PET/CT with 18F-FDG-labeled autologous leukocytes for the diagnosis of infected fluid collections in acute pancreatitis. J Nucl Med 2014; 55: 1267-1272
• 16 Bhatti M, Chapman P, Peters M. et al. Visualising E-selectin in the detection and evaluation of inflammatory bowel disease. Gut 1998; 43: 40-47
• 17 Bleeker-Rovers CP, Rennen HJ, Boerman OC. et al. 99mTc-labeled interleukin 8 for the scintigraphic detection of infection and inflammation: first clinical evaluation. J Nucl Med 2007; 48: 337-343
• 18 Bouter CMB, Sahlmann CO, Wester HJ. et al. Imaging chemikine receptor CXCR4 in infection of the bone with 68Ga-Pentixafor-PET/CT – first insights. Rome, Italy: Imaging Infection and Inflammation; 2016
• 19 Bouter CMB, Sahlmann CO, Wester HJ. et al. V13 Imaging chemokine receptor CXCR4 in inflammation of the bone with 68Ga-Pentixafor-PET/CT – first insights. Dresden, Germany: 2017 http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/abstract_detail.php?navId=216&aId=188
• 20 Britton KE, Wareham DW, Das SS. et al. Imaging bacterial infection with (99m)Tc-ciprofloxacin (Infecton). J Clin Pathol 2002; 55: 817-823
• 21 Bruijnen S, Tsang ASM, Raterman H. et al. B-cell imaging with zirconium-89 labelled rituximab PET-CT at baseline is associated with therapeutic response 24 weeks after initiation of rituximab treatment in rheumatoid arthritis patients. Arthritis Res Ther 2016; 18: 266
• 22 Burggasser G, Hurtl I, Hauff W. et al. Orbital scintigraphy with the somatostatin receptor tracer 99mTc-P829 in patients with Gravesʼ disease. J Nucl Med 2003; 44: 1547-1555
• 23 Carter SF, Scholl M, Almkvist O. et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 2012; 53: 37-46
• 24 Chapman PT, Jamar F, Keelan ET. et al. Use of a radiolabeled monoclonal antibody against E-selectin for imaging of endothelial activation in rheumatoid arthritis. Arthritis Rheum 1996; 39: 1371-1375
• 25 Chianelli M, Parisella MG, Visalli N. et al. Pancreatic scintigraphy with 99mTc-interleukin-2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy. Diabetes Metab Res Rev 2008; 24: 115-122
• 26 Conti F, Malviya G, Ceccarelli F. et al. Role of scintigraphy with (9)(9)mTc-infliximab in predicting the response of intraarticular infliximab treatment in patients with refractory monoarthritis. Eur J Nucl Med Mol Imaging 2012; 39: 1339-1347
• 27 Conti F, Priori R, Chimenti MS. et al. Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: a role for scintigraphy with 99mTc-infliximab. Arthritis Rheum 2005; 52: 1224-1226
• 28 Coughlin JM, Wang Y, Minn I. et al. Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players. JAMA Neurol 2017; 74: 67-74
• 29 Datz FL. Indium-111-labeled leukocytes for the detection of infection: current status. Semin Nucl Med 1994; 24: 92-109
• 30 Diaz Jr. LA, Foss CA, Thornton K. et al. Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT. PLoS One 2007; 2: e1007
• 31 Di Gialleonardo V, Signore A, Willemsen AT. et al. Pharmacokinetic modelling of N-(4-[(18)F]fluorobenzoyl)interleukin-2 binding to activated lymphocytes in an xenograft model of inflammation. Eur J Nucl Med Mol Imaging 2012; 39: 1551-1560
• 32 Duan L, Li XF, Lu KY. et al. [Clinical application of orbital scintigraphy with 99Tc(m)-octreotide in patients with thyroid associated ophthalmopathy]. Zhonghua Yan Ke Za Zhi 2006; 42: 1068-1072
• 33 Dumarey N, Blocklet D, Appelboom T. et al. Infecton is not specific for bacterial osteo-articular infective pathology. Eur J Nucl Med Mol Imaging 2002; 29: 530-535
• 34 Dumarey N, Egrise D, Blocklet D. et al. Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients. J Nucl Med 2006; 47: 625-632
• 35 Erba PA, Conti U, Lazzeri E. et al. Added value of 99mTc-HMPAO-labeled leukocyte SPECT/CT in the characterization and management of patients with infectious endocarditis. J Nucl Med 2012; 53: 1235-1243
• 36 Esposito G, Giovacchini G, Liow JS. et al. Imaging neuroinflammation in Alzheimer's disease with radiolabeled arachidonic acid and PET. J Nucl Med 2008; 49: 1414-1421
• 37 Evens N, Muccioli GG, Houbrechts N. et al. Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging. Nucl Med Biol 2009; 36: 455-465
• 38 Evens N, Vandeputte C, Muccioli GG. et al. Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging. Bioorg Med Chem 2011; 19: 4499-4505
• 39 Filippi L, Schillaci O. SPECT/CT with a hybrid camera: a new imaging modality for the functional anatomical mapping of infections. Expert Rev Med Devices 2006; 3: 699-703
• 40 Fischman AJ, Livni E, Babich J. et al. Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography. Antimicrob Agents Chemother 1992; 36: 2286-2292
• 41 Forstrom LA, Mullan BP, Hung JC. et al. 18F-FDG labelling of human leukocytes. Nucl Med Commun 2000; 21: 691-694
• 42 Galuska L, Leovey A, Szucs-Farkas Z. et al. Imaging of disease activity in Graves' orbitopathy with different methods: comparison of (99m)Tc-DTPA and (99m)Tc-depreotide single photon emission tomography, magnetic resonance imaging and clinical activity scores. Nucl Med Commun 2005; 26: 407-414
• 43 Glaudemans AW, Bonanno E, Galli F. et al. In vivo and in vitro evidence that (9)(9)mTc-HYNIC-interleukin-2 is able to detect T lymphocytes in vulnerable atherosclerotic plaques of the carotid artery. Eur J Nucl Med Mol Imaging 2014; 41: 1710-1719
• 44 Gormsen LC, Haraldsen A, Kramer S. et al. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis. EJNMMI Res 2016; 6: 52
• 45 Gowrishankar G, Namavari M, Jouannot EB. et al. Investigation of 6-[(1)(8)F]-fluoromaltose as a novel PET tracer for imaging bacterial infection. PLoS One 2014; 9: e107951
• 46 Granowitz EV, Porat R, Mier JW. et al. Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. Cytokine 1992; 4: 353-360
• 47 Gratz S, Rennen HJ, Boerman OC. et al. Rapid imaging of experimental colitis with (99m)Tc-interleukin-8 in rabbits. J Nucl Med 2001; 42: 917-923
• 48 Gratz S, Rennen HJ, Boerman OC. et al. (99m)Tc-interleukin-8 for imaging acute osteomyelitis. J Nucl Med 2001; 42: 1257-1264
• 49 Health USNIo. [124I]FIAU PET-CT Scanning in Patients With Pain in a Prosthetic Knee or Hip Joint (PJI). 2016 Im Internet: https://clinicaltrials.gov/ct2/show/NCT01705496
• 50 Hohloch K, Sahlmann CO, Lakhani VJ. et al. Tandem high-dose therapy in relapsed and refractory B-cell lymphoma: results of a prospective phase II trial of myeloablative chemotherapy, followed by escalated radioimmunotherapy with (131)I-anti-CD20 antibody and stem cell rescue. Ann Hematol 2011; 90: 1307-1315
• 51 Hubalewska-Dydejczyk A, Stompor T, Kalembkiewicz M. et al. Identification of inflamed atherosclerotic plaque using 123 I-labeled interleukin-2 scintigraphy in high-risk peritoneal dialysis patients: a pilot study. Perit Dial Int 2009; 29: 568-574
• 52 Jamar F, Chapman PT, Harrison AA. et al. Inflammatory arthritis: imaging of endothelial cell activation with an indium-111-labeled F(ab')2 fragment of anti-E-selectin monoclonal antibody. Radiology 1995; 194: 843-850
• 53 Jamar F, Chapman PT, Manicourt DH. et al. A comparison between 111In-anti-E-selectin mAb and 99Tcm-labelled human non-specific immunoglobulin in radionuclide imaging of rheumatoid arthritis. Br J Radiol 1997; 70: 473-481
• 54 Jamar F, Houssiau FA, Devogelaer JP. et al. Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis. Rheumatology (Oxford) 2002; 41: 53-61
• 55 Johansson A, Savitcheva I, Forsberg A. et al. [(11)C]-PIB imaging in patients with Parkinsonʼs disease: preliminary results. Parkinsonism Relat Disord 2008; 14: 345-347
• 56 Kahaly G, Diaz M, Hahn K. et al. Indium-111-pentetreotide scintigraphy in Graves' ophthalmopathy. J Nucl Med 1995; 36: 550-554
• 57 Keelan ET, Licence ST, Peters AM. et al. Characterization of E-selectin expression in vivo with use of a radiolabeled monoclonal antibody. Am J Physiol 1994; 266: H278-290
• 58 Kinne RW, Becker W, Schwab J. et al. Imaging rheumatoid arthritis joints with technetium-99m labelled specific anti-CD4- and non-specific monoclonal antibodies. Eur J Nucl Med 1994; 21: 176-180
• 59 Kinne RW, Wolski A, Palombo-Kinne E. et al. Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies. Nuklearmedizin 2002; 41: 129-134
• 60 Koch AE, Burrows JC, Haines GK. et al. Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab Invest 1991; 64: 313-320
• 61 Krassas GE, Doumas A, Kaltsas T. et al. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid 1999; 9: 47-52
• 62 Kriegsmann J, Keyszer GM, Geiler T. et al. Expression of E-selectin messenger RNA and protein in rheumatoid arthritis. Arthritis Rheum 1995; 38: 750-754
• 63 Kropholler MA, Boellaard R, Elzinga EH. et al. Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis. Eur J Nucl Med Mol Imaging 2009; 36: 624-631
• 64 Kwekkeboom DJ, Krenning EP, Kho GS. et al. Somatostatin receptor imaging in patients with sarcoidosis. Eur J Nucl Med 1998; 25: 1284-1292
• 65 Langer O, Brunner M, Zeitlinger M. et al. In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET. Eur J Nucl Med Mol Imaging 2005; 32: 143-150
• 66 Larikka MJ, Ahonen AK, Niemela O. et al. 99m Tc-ciprofloxacin (Infecton) imaging in the diagnosis of knee prosthesis infections. Nucl Med Commun 2002; 23: 167-170
• 67 Lebtahi R, Crestani B, Belmatoug N. et al. Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis. J Nucl Med 2001; 42: 21-26
• 68 Li X, Bauer W, Israel I. et al. Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI. Arterioscler Thromb Vasc Biol 2014; 34: 1661-1667
• 69 Liberatore M, Clemente M, Iurilli AP. et al. Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of technetium-99m human non-specific immunoglobulins, leucocytes and albumin nanocolloids. Eur J Nucl Med 1992; 19: 853-857
• 70 Loggia ML, Chonde DB, Akeju O. et al. Evidence for brain glial activation in chronic pain patients. Brain 2015; 138: 604-615
• 71 Love C, Tronco GG, Palestro CJ. Imaging of infection and inflammation with 99mTc-Fanolesomab. Q J Nucl Med Mol Imaging 2006; 50: 113-120
• 72 Malviya G, Anzola KL, Podesta E. et al. (99m)Tc-labeled rituximab for imaging B lymphocyte infiltration in inflammatory autoimmune disease patients. Mol Imaging Biol 2012; 14: 637-646
• 73 Malviya G, Conti F, Chianelli M. et al. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies. Eur J Nucl Med Mol Imaging 2010; 37: 386-398
• 74 Malviya G, D'Alessandria C, Bonanno E. et al. Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human T-lymphocytes. J Nucl Med 2009; 50: 1683-1691
• 75 Marcus C, Thakur ML, Huynh TV. et al. Imaging rheumatic joint diseases with anti-T lymphocyte antibody OKT-3. Nucl Med Commun 1994; 15: 824-830
• 76 Martins FP, Gutfilen B, de Souza SA. et al. Monitoring rheumatoid arthritis synovitis with 99mTc-anti-CD3. Br J Radiol 2008; 81: 25-29
• 77 Martins FP, Souza SA, Goncalves RT. et al. Preliminary results of [99mTc]OKT3 scintigraphy to evaluate acute rejection in renal transplants. Transplant Proc 2004; 36: 2664-2667
• 78 McKenzie R, Fried MW, Sallie R. et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995; 333: 1099-1105
• 79 Meller J, Liersch T, Oezerden MM. et al. Targeting NCA-95 and other granulocyte antigens and receptors with radiolabeled monoclonal antibodies (Mabs). Q J Nucl Med Mol Imaging 2010; 54: 582-598
• 80 Meller J, Sahlmann CO, Ivančević V. Differentialindikation für verschiedene radioaktive Arzneimittel. Im Internet: http://www.awmf.org/leitlinien/detail/ll/031-018.html Zugriff: 1.3.2017
• 81 Migliore A, Signore A, Capuano A. et al. Relevance of 99mTc-HYNIC-tir-octreotide scintigraphy in a patient affected by sarcoidosis with lung and joints involvement and secondary Sjogrenʼs syndrome treated with infliximab: case report. Eur Rev Med Pharmacol Sci 2008; 12: 127-130
• 82 Muylle K, Flamen P, Vugts DJ. et al. Tumour targeting and radiation dose of radioimmunotherapy with (90)Y-rituximab in CD20+ B-cell lymphoma as predicted by (89)Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab. Eur J Nucl Med Mol Imaging 2015; 42: 1304-1314
• 83 Nazari B, Azizmohammadi Z, Rajaei M. et al. Role of 99mTc-ubiquicidin 29-41 scintigraphy to monitor antibiotic therapy in patients with orthopedic infection: a preliminary study. Nucl Med Commun 2011; 32: 745-751
• 84 Niccolini F, Su P, Politis M. PET in multiple sclerosis. Clin Nucl Med 2015; 40: e46-e52
• 85 Nobashi T, Nakamoto Y, Kubo T. et al. The utility of PET/CT with (68)Ga-DOTATOC in sarcoidosis: comparison with (67)Ga-scintigraphy. Ann Nucl Med 2016; 30: 544-552
• 86 Omata M, Matsui N, Inomata N. et al. Protective effects of polysaccharide fucoidin on myocardial ischemia-reperfusion injury in rats. J Cardiovasc Pharmacol 1997; 30: 717-724
• 87 Opalinska M, Stompor T, Pach D. et al. Imaging of inflamed carotid artery atherosclerotic plaques with the use of 99mTc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients. Eur J Nucl Med Mol Imaging 2012; 39: 673-682
• 88 Osman S, Danpure HJ. The use of 2-[18F]fluoro-2-deoxy-D-glucose as a potential in vitro agent for labelling human granulocytes for clinical studies by positron emission tomography. Int J Rad Appl Instrum B 1992; 19: 183-190
• 89 Ostovar A, Assadi M, Vahdat K. et al. A pooled analysis of diagnostic value of (99m)Tc-ubiquicidin (UBI) scintigraphy in detection of an infectious process. Clin Nucl Med 2013; 38: 413-416
• 90 Palestro CJ. Radionuclide imaging of osteomyelitis. Semin Nucl Med 2015; 45: 32-46
• 91 Papos M, Varkonyi A, Lang J. et al. HM-PAO-labeled leukocyte scintigraphy in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1996; 23: 547-552
• 92 Paran D, Elkayam O, Mayo A. et al. A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis. Ann Rheum Dis 2001; 60: 888-891
• 93 Pio BS, Byrne FR, Aranda R. et al. Noninvasive quantification of bowel inflammation through positron emission tomography imaging of 2-deoxy-2-[18F]fluoro-D-glucose-labeled white blood cells. Mol Imaging Biol 2003; 5: 271-277
• 94 Rennen HJ, Boerman OC, Oyen WJ. et al. Kinetics of 99mTc-labeled interleukin-8 in experimental inflammation and infection. J Nucl Med 2003; 44: 1502-1509
• 95 Rini JN, Bhargava KK, Tronco GG. et al. PET with FDG-labeled leukocytes versus scintigraphy with 111In-oxine-labeled leukocytes for detection of infection. Radiology 2006; 238: 978-987
• 96 Rodriguez-Vieitez E, Carter SF, Chiotis K. et al. Comparison of Early-Phase 11C-Deuterium-l-Deprenyl and 11C-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease. J Nucl Med 2016; 57: 1071-1077
• 97 Rouzet F, Bachelet-Violette L, Alsac JM. et al. Radiolabeled fucoidan as a p-selectin targeting agent for in vivo imaging of platelet-rich thrombus and endothelial activation. J Nucl Med 2011; 52: 1433-1440
• 98 Saeed S, Zafar J, Khan B. et al. Utility of (9)(9)mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection. Eur J Nucl Med Mol Imaging 2013; 40: 737-743
• 99 Santillo AF, Gambini JP, Lannfelt L. et al. In vivo imaging of astrocytosis in Alzheimer's disease: an (1)(1)C-L-deuteriodeprenyl and PIB PET study. Eur J Nucl Med Mol Imaging 2011; 38: 2202-2208
• 100 Scholl M, Carter SF, Westman E. et al. Early astrocytosis in autosomal dominant Alzheimerʼs disease measured in vivo by multi-tracer positron emission tomography. Sci Rep 2015; 5 Art. Nr.16404 DOI: 10.1038/srep16404.
• 101 Signore A, Capriotti G, Chianelli M. et al. Detection of insulitis by pancreatic scintigraphy with 99mTc-labeled IL-2 and MRI in patients with LADA (Action LADA 10). Diabetes Care 2015; 38: 652-658
• 102 Signore A, Chianelli M, Annovazzi A. et al. 123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn's disease. J Nucl Med 2000; 41: 242-249
• 103 Sonmezoglu K, Sonmezoglu M, Halac M. et al. Usefulness of 99mTc-ciprofloxacin (infecton) scan in diagnosis of chronic orthopedic infections: comparative study with 99mTc-HMPAO leukocyte scintigraphy. J Nucl Med 2001; 42: 567-574
• 104 Takeba Y, Suzuki N, Takeno M. et al. Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis. Arthritis Rheum 1997; 40: 2128-2138
• 105 Uhlen M, Fagerberg L, Hallstrom BM. et al. Proteomics. Tissue-based map of the human proteome. Science 2015; 347: 1260419
• 106 Utset TO, Auger JA, Peace D. et al. Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial. J Rheumatol 2002; 29: 1907-1913
• 107 van der Doef TF, de Witte LD, Sutterland AL. et al. In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr 2016; 2: 16031
• 108 van der Laken CJ, Boerman OC, Oyen WJ. et al. Imaging of infection in rabbits with radioiodinated interleukin-1 (alpha and beta), its receptor antagonist and a chemotactic peptide: a comparative study. Eur J Nucl Med 1998; 25: 347-352
• 109 van der Laken CJ, Boerman OC, Oyen WJ. et al. In vivo expression of interleukin-1 receptors during various experimentally induced inflammatory conditions. J Infect Dis 1998; 177: 1398-1401
• 110 van der Laken CJ, Elzinga EH, Kropholler MA. et al. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum 2008; 58: 3350-3355
• 111 Van Hemert FJ, Voermans C, Van Eck-Smit BL. et al. Labeling monocytes for imaging chronic inflammation. Q J Nucl Med Mol Imaging 2009; 53: 78-88
• 112 Vinjamuri S, Hall AV, Solanki KK. et al. Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection. Lancet 1996; 347: 233-235
• 113 Vis R, Malviya G, Signore A. et al. (9)(9)mTc-anti-TNF-alpha antibody for the imaging of disease activity in pulmonary sarcoidosis. Eur Respir J 2016; 47: 1198-1207
• 114 Walker RC, Jones-Jackson LB, Martin W. et al. New imaging tools for the diagnosis of infection. Future Microbiol 2007; 2: 527-554
• 115 Weinstein EA, Ordonez AA, DeMarco VP. et al. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography. Sci Transl Med 2014; 6: 259-279
• 116 Yilmaz S, Aliyev A, Ekmekcioglu O. et al. Comparison of FDG and FDG-labeled leukocytes PET/CT in diagnosis of infection. Nuklearmedizin 2015; 54: 262-271
• 117 Zhang XM, Zhang HH, McLeroth P. et al. [(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection. Nucl Med Biol 2016; 43: 273-279
• 118 Zhao R, Wang J, Deng J. et al. Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Gravesʼ ophthalmopathy. Am J Nucl Med Mol Imaging 2012; 2: 242-247
• 119 Zhu W, Yao S, Xing H. et al. Biodistribution and Radiation Dosimetry of the Enterobacteriaceae-Specific Imaging Probe [(18)F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers. Mol Imaging Biol 2016; 18: 782-787
• 120 Zurcher NR, Loggia ML, Lawson R. et al. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin 2015; 7: 409-414