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Clinical applications in molecular imaging

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Abstract

Molecular imaging is aimed at the noninvasive in vivo characterization and measurement of processes at a cellular and molecular level with clinical imaging methods. Contrast agents are constructed to target markers that are specific either for certain diseases or for functional states of specialized tissues. Efforts are currently focused mainly on processes involved in angiogenesis, inflammation, and apoptosis. Cell tracking is performed for diagnostic purposes as well as for monitoring of novel cell therapies. Visualization of these processes would provide more precise information about disease expansion as well as treatment response, and could lead to a more individualized therapy for patients. Many attempts have shown promising results in preclinical studies; however, translation into the clinic remains a challenge. This applies especially to paediatrics because of more stringent safety concerns and the low prevalence of individual diseases. The most promising modalities for clinical translation are nuclear medicine methods (positron emission tomography [PET] and single photon emission CT [SPECT]) due to their high sensitivity, which allows concentrations below biological activity. However, special dose consideration is required for any application of ionizing radiation especially in children. While very little has been published on molecular imaging in a paediatric patient population beyond fluorodeoxyglucose (FDG)-PET and metaiodobenzylguanidine (MIBG) tracers, this review will attempt to discuss approaches that we believe have promise for paediatric imaging. These will include agents that already reached clinical trials as well as preclinical developments with high potential for clinical application.

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References

  1. Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333

    CAS  PubMed  Google Scholar 

  2. Grimm J, Wunder A (2005) Current state of molecular imaging research. Rofo 177:326–337

    CAS  PubMed  Google Scholar 

  3. Frangioni JV (2006) Translating in vivo diagnostics into clinical reality. Nat Biotechnol 24:909–913

    Article  CAS  PubMed  Google Scholar 

  4. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  5. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580

    Article  CAS  PubMed  Google Scholar 

  6. Blankenberg FG (2008) In vivo imaging of apoptosis. Cancer Biol Ther 7:1525–1532

    Article  CAS  PubMed  Google Scholar 

  7. De Saint-Hubert M, Prinsen K, Mortelmans L et al (2009) Molecular imaging of cell death. Methods 48:178–187

    Article  PubMed  Google Scholar 

  8. Ventura A, Kirsch DG, McLaughlin ME et al (2007) Restoration of p53 function leads to tumour regression in vivo. Nature 445:661–665

    Article  CAS  PubMed  Google Scholar 

  9. Fadok VA, Voelker DR, Campbell PA et al (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216

    CAS  PubMed  Google Scholar 

  10. Boersma HH, Kietselaer BL, Stolk LM et al (2005) Past, present, and future of annexin A5: from protein discovery to clinical applications. J Nucl Med 46:2035–2050

    CAS  PubMed  Google Scholar 

  11. van de Wiele C, Lahorte C, Vermeersch H et al (2003) Quantitative tumor apoptosis imaging using technetium-99 m-HYNIC annexin V single photon emission computed tomography. J Clin Oncol 21:3483–3487

    Article  PubMed  Google Scholar 

  12. Haas RL, de Jong D, Valdes Olmos RA et al (2004) In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 59:782–787

    Article  PubMed  Google Scholar 

  13. Kurihara H, Yang DJ, Cristofanilli M et al (2008) Imaging and dosimetry of 99mTc EC annexin V: preliminary clinical study targeting apoptosis in breast tumors. Appl Radiat Isot 66:1175–1182

    Article  CAS  PubMed  Google Scholar 

  14. Belhocine T, Steinmetz N, Hustinx R et al (2002) Increased uptake of the apoptosis-imaging agent (99 m)Tc recombinant human annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res 8:2766–2774

    CAS  PubMed  Google Scholar 

  15. Thimister PW, Hofstra L, Liem IH et al (2003) In vivo detection of cell death in the area at risk in acute myocardial infarction. J Nucl Med 44:391–396

    PubMed  Google Scholar 

  16. Lorberboym M, Blankenberg FG, Sadeh M et al (2006) In vivo imaging of apoptosis in patients with acute stroke: correlation with blood-brain barrier permeability. Brain Res 1103:13–19

    Article  CAS  PubMed  Google Scholar 

  17. Kietselaer BL, Reutelingsperger CP, Boersma HH et al (2007) Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure. J Nucl Med 48:562–567

    Article  CAS  PubMed  Google Scholar 

  18. Van den Brande JM, Koehler TC, Zelinkova Z et al (2007) Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn’s disease. Gut 56:509–517

    Article  PubMed  Google Scholar 

  19. Yagle KJ, Eary JF, Tait JF et al (2005) Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med 46:658–666

    CAS  PubMed  Google Scholar 

  20. Murakami Y, Takamatsu H, Taki J et al (2004) 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur J Nucl Med Mol Imaging 31:469–474

    Article  CAS  PubMed  Google Scholar 

  21. Zhang X, Paule MG, Newport GD et al (2009) A minimally invasive, translational biomarker of ketamine-induced neuronal death in rats: microPET Imaging using 18F-annexin V. Toxicol Sci 111:355–361

    Article  CAS  PubMed  Google Scholar 

  22. Sosnovik DE, Garanger E, Aikawa E et al (2009) Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed-enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: potential for midmyocardial salvage in acute ischemia. Circ Cardiovasc Imaging 2:460–467

    Article  PubMed  Google Scholar 

  23. Smith BR, Heverhagen J, Knopp M et al (2007) Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI). Biomed Microdevices 9:719–727

    Article  PubMed  Google Scholar 

  24. Cohen A, Shirvan A, Levin G et al (2009) From the Gla domain to a novel small-molecule detector of apoptosis. Cell Res 19:625–637

    Article  CAS  PubMed  Google Scholar 

  25. Grimberg H, Levin G, Shirvan A et al (2009) Monitoring of tumor response to chemotherapy in vivo by a novel small-molecule detector of apoptosis. Apoptosis 14:257–267

    Article  CAS  PubMed  Google Scholar 

  26. Aird WC (2005) Spatial and temporal dynamics of the endothelium. J Thromb Haemost 3:1392–1406

    Article  CAS  PubMed  Google Scholar 

  27. Endemann DH, Schiffrin EL (2004) Endothelial dysfunction. J Am Soc Nephrol 15:1983–1992

    Article  CAS  PubMed  Google Scholar 

  28. Reynolds PR, Larkman DJ, Haskard DO et al (2006) Detection of vascular expression of E-selectin in vivo with MR imaging. Radiology 241:469–476

    Article  PubMed  Google Scholar 

  29. Kaufmann BA, Carr CL, Belcik JT et al (2010) Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease. Arterioscler Thromb Vasc Biol 30:54–59

    Article  CAS  PubMed  Google Scholar 

  30. Behm CZ, Kaufmann BA, Carr C et al (2008) Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation 117:2902–2911

    Article  CAS  PubMed  Google Scholar 

  31. Boutry S, Burtea C, Laurent S et al (2005) Magnetic resonance imaging of inflammation with a specific selectin-targeted contrast agent. Magn Reson Med 53:800–807

    Article  CAS  PubMed  Google Scholar 

  32. Nahrendorf M, Jaffer FA, Kelly KA et al (2006) Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114:1504–1511

    Article  CAS  PubMed  Google Scholar 

  33. Funovics M, Montet X, Reynolds F et al (2005) Nanoparticles for the optical imaging of tumor E-selectin. Neoplasia 7:904–911

    Article  CAS  PubMed  Google Scholar 

  34. Mulder WJ, Strijkers GJ, Griffioen AW et al (2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug Chem 15:799–806

    Article  CAS  PubMed  Google Scholar 

  35. Ferrante EA, Pickard JE, Rychak J et al (2009) Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release 140:100–107

    Article  CAS  PubMed  Google Scholar 

  36. Bachmann C, Klibanov AL, Olson TS et al (2006) Targeting mucosal addressin cellular adhesion molecule (MadCAM)-1 to noninvasively image experimental Crohn’s disease. Gastroenterology 130:8–16

    Article  CAS  PubMed  Google Scholar 

  37. Jamar F, Houssiau FA, Devogelaer JP et al (2002) Scintigraphy using a technetium 99 m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis. Rheumatology (Oxford) 41:53–61

    Article  CAS  Google Scholar 

  38. Kiessling F (2008) Noninvasive cell tracking. Handb Exp Pharmacol 185:305–321

    Article  CAS  PubMed  Google Scholar 

  39. Grimm J, Kircher MF, Weissleder R (2007) Cell tracking. Principles and applications. Radiologe 47:25–33

    Article  CAS  PubMed  Google Scholar 

  40. Hofmann M, Wollert KC, Meyer GP et al (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 111:2198–2202

    Article  PubMed  Google Scholar 

  41. Dousset V, Brochet B, Deloire MS et al (2006) MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium. AJNR 27:1000–1005

    CAS  PubMed  Google Scholar 

  42. Saleh A, Schroeter M, Jonkmanns C et al (2004) In vivo MRI of brain inflammation in human ischaemic stroke. Brain 127:1670–1677

    Article  PubMed  Google Scholar 

  43. Trivedi RA, Mallawarachi C, U-King-Im JM et al (2006) Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol 26:1601–1606

    Article  CAS  PubMed  Google Scholar 

  44. Bennink RJ, Thurlings RM, van Hemert FJ et al (2008) Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in patients with rheumatoid arthritis. J Nucl Med 49:1380–1385

    Article  PubMed  Google Scholar 

  45. Thoeny HC, Triantafyllou M, Birkhaeuser FD et al (2009) Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients. Eur Urol 55:761–769

    Article  PubMed  Google Scholar 

  46. Kimura K, Tanigawa N, Matsuki M et al (2009) High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results. Breast Cancer 17:241–246

    Article  PubMed  Google Scholar 

  47. Pultrum BB, van der Jagt EJ, van Westreenen HL et al (2009) Detection of lymph node metastases with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in oesophageal cancer: a feasibility study. Cancer Imaging 9:19–28

    Article  CAS  PubMed  Google Scholar 

  48. Tokuhara T, Tanigawa N, Matsuki M et al (2008) Evaluation of lymph node metastases in gastric cancer using magnetic resonance imaging with ultrasmall superparamagnetic iron oxide (USPIO): diagnostic performance in post-contrast images using new diagnostic criteria. Gastric Cancer 11:194–200

    Article  PubMed  Google Scholar 

  49. Modak S, Cheung NK (2010) Neuroblastoma: Therapeutic strategies for a clinical enigma. Cancer Treat Rev 36:307–317

    Article  CAS  PubMed  Google Scholar 

  50. Beckmann N, Cannet C, Fringeli-Tanner M et al (2003) Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation. Magn Reson Med 49:459–467

    Article  CAS  PubMed  Google Scholar 

  51. Kanno S, Lee PC, Dodd SJ et al (2000) A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection. J Thorac Cardiovasc Surg 120:923–934

    Article  CAS  PubMed  Google Scholar 

  52. Kanno S, Wu YJ, Lee PC et al (2001) Macrophage accumulation associated with rat cardiac allograft rejection detected by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide particles. Circulation 104:934–938

    Article  CAS  PubMed  Google Scholar 

  53. Mulder WJ, Strijkers GJ, Briley-Saboe KC et al (2007) Molecular imaging of macrophages in atherosclerotic plaques using bimodal PEG-micelles. Magn Reson Med 58:1164–1170

    Article  PubMed  Google Scholar 

  54. Kircher MF, Grimm J, Swirski FK et al (2008) Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions. Circulation 117:388–395

    Article  PubMed  Google Scholar 

  55. Pittet MJ, Grimm J, Berger CR et al (2007) In vivo imaging of T cell delivery to tumors after adoptive transfer therapy. Proc Natl Acad Sci USA 104:12457–12461

    Article  CAS  PubMed  Google Scholar 

  56. Tawakol A, Migrino RQ, Bashian GG et al (2006) In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 48:1818–1824

    Article  PubMed  Google Scholar 

  57. Azzi J, Geara AS, El-Sayegh S et al (2010) Immunological aspects of pancreatic islet cell transplantation. Expert Rev Clin Immunol 6:111–124

    Article  PubMed  Google Scholar 

  58. Kraitchman DL, Bulte JW (2009) In vivo imaging of stem cells and Beta cells using direct cell labeling and reporter gene methods. Arterioscler Thromb Vasc Biol 29:1025–1030

    Article  CAS  PubMed  Google Scholar 

  59. Turkbey B, Kobayashi H, Ogawa M et al (2009) Imaging of tumor angiogenesis: functional or targeted? AJR 193:304–313

    Article  PubMed  Google Scholar 

  60. Nessa A, Latif SA, Siddiqui NI et al (2009) Angiogenesis-a novel therapeutic approach for ischemic heart disease. Mymensingh Med J 18:264–272

    CAS  PubMed  Google Scholar 

  61. Sneider EB, Nowicki PT, Messina LM (2009) Regenerative medicine in the treatment of peripheral arterial disease. J Cell Biochem 108:753–761

    Article  CAS  PubMed  Google Scholar 

  62. Baeriswyl V, Christofori G (2009) The angiogenic switch in carcinogenesis. Semin Cancer Biol 19:329–337

    Article  CAS  PubMed  Google Scholar 

  63. Cortes-Funes H (2009) The role of antiangiogenesis therapy: bevacizumab and beyond. Clin Transl Oncol 11:349–355

    Article  CAS  PubMed  Google Scholar 

  64. Jayson GC, Zweit J, Jackson A et al (2002) Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J Natl Cancer Inst 94:1484–1493

    CAS  PubMed  Google Scholar 

  65. Blankenberg FG, Levashova Z, Sarkar SK et al (2010) Noninvasive assessment of tumor VEGF receptors in response to treatment with pazopanib: a molecular imaging study. Transl Oncol 3:56–64

    PubMed  Google Scholar 

  66. Dijkgraaf I, Boerman OC (2009) Radionuclide imaging of tumor angiogenesis. Cancer Biother Radiopharm 24:637–647

    Article  CAS  PubMed  Google Scholar 

  67. Schnell O, Krebs B, Carlsen J et al (2009) Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography. Neuro Oncol 11:861–870

    Article  PubMed  Google Scholar 

  68. Beer AJ, Niemeyer M, Carlsen J et al (2008) Patterns of alphavbeta3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J Nucl Med 49:255–259

    Article  PubMed  Google Scholar 

  69. Beer AJ, Grosu AL, Carlsen J et al (2007) [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 13:6610–6616

    Article  CAS  PubMed  Google Scholar 

  70. Beer AJ, Haubner R, Sarbia M et al (2006) Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res 12:3942–3949

    Article  CAS  PubMed  Google Scholar 

  71. Bach-Gansmo T, Bogsrud TV, Skretting A (2008) Integrin scintimammography using a dedicated breast imaging, solid-state gamma-camera and (99 m)Tc-labelled NC100692. Clin Physiol Funct Imaging 28:235–239

    Article  PubMed  Google Scholar 

  72. Kenny LM, Coombes RC, Oulie I et al (2008) Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med 49:879–886

    Article  PubMed  Google Scholar 

  73. Chengazi VU, Feneley MR, Ellison D et al (1997) Imaging prostate cancer with technetium-99m-7E11-C5.3 (CYT-351). J Nucl Med 38:675–682

    CAS  PubMed  Google Scholar 

  74. Morris MJ, Pandit-Taskar N, Divgi CR et al (2007) Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors. Clin Cancer Res 13:2707–2713

    Article  CAS  PubMed  Google Scholar 

  75. Bakhshi S, Radhakrishnan V (2010) Prognostic markers in osteosarcoma. Expert Rev Anticancer Ther 10:271–287

    Article  PubMed  Google Scholar 

  76. Wachtel M, Schafer BW (2010) Targets for cancer therapy in childhood sarcomas. Cancer Treat Rev 36:318–327

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

The authors would like to thank Alexandra Sarkozy for help with the literature search.

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  1. Jan Grimm

    Present address: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10044, USA

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  1. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Carola Heneweer & Jan Grimm

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  1. Carola Heneweer
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Correspondence to Jan Grimm.

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Heneweer, C., Grimm, J. Clinical applications in molecular imaging. Pediatr Radiol 41, 199–207 (2011). https://doi.org/10.1007/s00247-010-1902-5

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