Abstract
The use of contrast agents is an important component of diagnostic biomedical imaging, both in preclinical and clinical applications. Injected contrast agents both increase the sensitivity and the specificity of disease detection. This chapter provides an overview of the most important design considerations of contrast materials and how this affects their utility. The consequences of changes in the composition, size and other key design features of the contrast agents are mainly illustrated with examples of the use of dendrimers. Dendrimers represent a unique class of materials, the synthesis of which can be very well controlled to tune their size and chemical properties. Dendrimers can readily be equipped with a great variety of labels to enable their detection with optical, nuclear and/or magnetic resonance imaging (MRI) techniques. The emphasis of the chapter will be on the use of dendrimers for contrast-enhanced MRI, an application domain for which they have been shown to be particularly suited. Special attention will be paid to the pharmacokinetic and pharmacodynamic behaviour of the contrast agents, as this determines to a large extent the diagnostic questions they can address and their safety profile.
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Abbreviations
- ADME:
-
Absorption, distribution, metabolism, and excretion
- BBB:
-
Blood–brain barrier
- CEST:
-
Chemical exchange saturation transfer
- CNR:
-
Contrast-to-noise ratio
- CT:
-
Computed tomography
- DCE-MRI:
-
Dynamic contrast-enhanced magnetic resonance imaging
- DO3A:
-
1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide
- DOTA:
-
1,4,7,10-tetraazacyclododecane tetraacetic acid
- DTPA:
-
Diethylenetriaminepentaacetic acid
- EPR effect:
-
Enhanced permeability and retention effect
- G:
-
Generation
- HER2:
-
Human epidermal growth factor receptor 2
- MRI:
-
Magnetic resonance imaging
- OI:
-
Optical imaging
- PAMAM dendrimers:
-
Poly(amidoamine) dendrimers
- PEG:
-
Poly(ethylene glycol)
- PEO:
-
Poly(ethylene oxide)
- PET:
-
Positron emission tomography
- PPI dendrimers:
-
Poly(propylene imine) dendrimers
- QD:
-
Quantum dot
- RES:
-
Reticuloendothelial system
- SNR:
-
Signal-to-noise ratio
- SPECT:
-
Single-photon emission computed tomography
- US:
-
Ultrasound
References
Agarwal A, Saraf S, Asthana A, Gupta U, Gajbhiye V, Jain NK. Ligand based dendritic systems for tumor targeting. Int J Pharm. 2008;350(1–2):3–13. doi:10.1016/j.ijpharm.2007.09.024.
Aime S, Botta M, Fasano M, Terreno E. Lanthanide(III) chelates for NMR biomedical applications. Chem Soc Rev. 1998;27(1):19–29. doi:10.1039/A827019z.
Asati A, Santra S, Kaittanis C, Perez JM. Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano. 2010;4(9):5321–31. doi:10.1021/nn100816s.
Baker JR, Jr. Dendrimer-based nanoparticles for cancer therapy. Hematology Am Soc Hematol Educ Program. 2009:708–19. doi:10.1182/asheducation-2009.1.708.
Barrett T, Ravizzini G, Choyke PL, Kobayashi H. Dendrimers in medical nanotechnology. IEEE Eng Med Biol Mag. 2009;28(1):12–22. doi:10.1109/MEMB.2008.931012.
Boas U, Heegaard PM. Dendrimers in drug research. Chem Soc Rev. 2004;33(1):43–63. doi:10.1039/b309043b.
Bosman AW, Janssen HM, Meijer EW. About dendrimers: structure, physical properties, and applications. Chem Rev. 1999;99(7):1665–88.
Bumb A, Brechbiel MW, Choyke P. Macromolecular and dendrimer-based magnetic resonance contrast agents. Acta Radiol. 2010;51(7):751–67. doi:10.3109/02841851.2010.491091.
Cai H, Li K, Li J, Wen S, Chen Q, Shen M, et al. Dendrimer-assisted formation of Fe3O4/Au nanocomposite particles for targeted dual mode CT/MR imaging of tumors. Small. 2015;11(35):4584–93. doi:10.1002/smll.201500856.
Chen K, Chen X. Design and development of molecular imaging probes. Curr Top Med Chem. 2010;10(12):1227–36.
Chen J, Lanza GM, Wickline SA. Quantitative magnetic resonance fluorine imaging: today and tomorrow. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010;2(4):431–40. doi:10.1002/wnan.87.
Chen WT, Shih TT, Chen RC, Tu SY, Hsieh WY, Yang PC. Integrin alphavbeta3-targeted dynamic contrast-enhanced magnetic resonance imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic treatment response in a mouse xenograft tumor model. Mol Imaging. 2012;11(4):286–300.
Chen Q, Li K, Wen S, Liu H, Peng C, Cai H, et al. Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles. Biomaterials. 2013;34(21):5200–9. doi:10.1016/j.biomaterials.2013.03.009.
Chen Q, Wang H, Liu H, Wen S, Peng C, Shen M, et al. Multifunctional dendrimer-entrapped gold nanoparticles modified with RGD peptide for targeted computed tomography/magnetic resonance dual-modal imaging of tumors. Anal Chem. 2015;87(7):3949–56. doi:10.1021/acs.analchem.5b00135.
Cheng Y, Zhao L, Li Y, Xu T. Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem Soc Rev. 2011;40(5):2673–703. doi:10.1039/c0cs00097c.
Choi HS, Frangioni JV. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol Imaging. 2010;9(6):291–310.
Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165–70. doi:10.1038/nbt1340.
Criscione JM, Le BL, Stern E, Brennan M, Rahner C, Papademetris X, et al. Self-assembly of pH-responsive fluorinated dendrimer-based particulates for drug delivery and noninvasive imaging. Biomaterials. 2009;30(23–24):3946–55. doi:10.1016/j.biomaterials.2009.04.014.
de Kort DW, van Duynhoven JP, Hoeben FJ, Janssen HM, Van As H. NMR nanoparticle diffusometry in hydrogels: enhancing sensitivity and selectivity. Anal Chem. 2014;86(18):9229–35. doi:10.1021/ac502211q.
de Lussanet QG, Langereis S, Beets-Tan RG, van Genderen MH, Griffioen AW, van Engelshoven JM, et al. Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice. Radiology. 2005;235(1):65–72. doi:10.1148/radiol.2351040411.
de Rosales RT. Potential clinical applications of bimodal PET-MRI or SPECT-MRI agents. J Labelled Comp Radiopharm. 2014;57(4):298–303. doi:10.1002/jlcr.3154.
Gajbhiye V, Kumar PV, Tekade RK, Jain NK. Pharmaceutical and biomedical potential of PEGylated dendrimers. Curr Pharm Design. 2007;13(4):415–29. doi:10.2174/138161207780162999.
Geraldes CFGC, Laurent S. Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media Mol Imaging. 2009;4(1):1–23. doi:10.1002/cmmi.265.
Gillies ER, Dy E, Frechet JM, Szoka FC. Biological evaluation of polyester dendrimer: poly(ethylene oxide) “bow-tie” hybrids with tunable molecular weight and architecture. Mol Pharm. 2005;2(2):129–38. doi:10.1021/mp049886u.
Gnanasegaran G, Ballinger JR. Molecular imaging agents for SPECT (and SPECT/CT). Eur J Nucl Med Mol Imaging. 2014;41 Suppl 1:S26–35. doi:10.1007/s00259-013-2643-0.
Godin B, Tasciotti E, Liu X, Serda RE, Ferrari M. Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics. Acc Chem Res. 2011;44(10):979–89. doi:10.1021/ar200077p.
Hak S, Sanders HM, Agrawal P, Langereis S, Grull H, Keizer HM, et al. A high relaxivity Gd(III)DOTA-DSPE-based liposomal contrast agent for magnetic resonance imaging. Eur J Pharm Biopharm. 2009;72(2):397–404. doi:10.1016/j.ejpb.2008.09.017.
Han LA, Li JF, Huang SX, Huang RQ, Liu SH, Hu X, et al. Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent. Biomaterials. 2011;32(11):2989–98. doi:10.1016/j.biomaterials.2011.01.005.
Huang R, Wang M, Zhu Y, Conti PS, Chen K. Development of PET probes for cancer imaging. Curr Top Med Chem. 2015;15(8):795–819.
Huang Z, Sengar RS, Nigam A, Abadjian MC, Potter DM, Grotjahn DB, et al. A fluorinated dendrimer-based nanotechnology platform: new contrast agents for high field imaging. Invest Radiol. 2010;45(10):641–54. doi:10.1097/RLI.0b013e3181ee6e06.
Iagaru A, Gambhir SS. Imaging tumor angiogenesis: the road to clinical utility. AJR Am J Roentgenol. 2013;201(2):W183–91. doi:10.2214/AJR.12.8568.
Jacobs I, Strijkers GJ, Keizer HM, Janssen HM, Nicolay K, Schabel MC. A novel approach to tracer-kinetic modeling for (macromolecular) dynamic contrast-enhanced MRI. Magn Reson Med. 2015;75(3):1142–53. doi:10.1002/mrm.25704.
Jain K, Kesharwani P, Gupta U, Jain NK. Dendrimer toxicity: Let’s meet the challenge. Int J Pharm. 2010;394(1–2):122–42. doi:10.1016/j.ijpharm.2010.04.027.
James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012;92(2):897–965. doi:10.1152/physrev.00049.2010.
Jaszberenyi Z, Moriggi L, Schmidt P, Weidensteiner C, Kneuer R, Merbach AE, et al. Physicochemical and MRI characterization of Gd3+ -loaded polyamidoamine and hyperbranched dendrimers. J Biol Inorg Chem. 2007;12(3):406–20. doi:10.1007/s00775-006-0197-3.
Jiang ZX, Liu X, Jeong EK, Yu YB. Symmetry-guided design and fluorous synthesis of a stable and rapidly excreted imaging tracer for (19)F MRI. Angew Chem Int Ed Engl. 2009;48(26):4755–8. doi:10.1002/anie.200901005.
Kaminskas LM, Porter CJ. Targeting the lymphatics using dendritic polymers (dendrimers). Adv Drug Deliv Rev. 2011;63(10–11):890–900. doi:10.1016/j.addr.2011.05.016.
Kannan RM, Nance E, Kannan S, Tomalia DA. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med. 2014;276(6):579–617. doi:10.1111/joim.12280.
Kesharwani P, Iyer AK. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discov Today. 2015;20(5):536–47. doi:10.1016/j.drudis.2014.12.012.
Khemthongcharoen N, Jolivot R, Rattanavarin S, Piyawattanametha W. Advances in imaging probes and optical microendoscopic imaging techniques for early in vivo cancer assessment. Adv Drug Deliv Rev. 2014;74:53–74. doi:10.1016/j.addr.2013.09.012.
Kiessling F, Fokong S, Bzyl J, Lederle W, Palmowski M, Lammers T. Recent advances in molecular, multimodal and theranostic ultrasound imaging. Adv Drug Deliv Rev. 2014;72:15–27. doi:10.1016/j.addr.2013.11.013.
Kobayashi H, Brechbiel MW. Nano-sized MRI contrast agents with dendrimer cores. Adv Drug Deliv Rev. 2005;57(15):2271–86. doi:10.1016/j.addr.2005.09.016.
Kobayashi H, Wu C, Kim MK, Paik CH, Carrasquillo JA, Brechbiel MW. Evaluation of the in vivo biodistribution of indium-111 and yttrium-88 labeled dendrimer-1B4M-DTPA and its conjugation with anti-Tac monoclonal antibody. Bioconjug Chem. 1999;10(1):103–11. doi:10.1021/bc980091d.
Kobayashi H, Sato N, Saga T, Nakamoto Y, Ishimori T, Toyama S, et al. Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity. Eur J Nucl Med. 2000;27(9):1334–9.
Kobayashi H, Kawamoto S, Saga T, Sato N, Hiraga A, Ishimori T, et al. Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents. Magn Reson Med. 2001a;46(4):781–8.
Kobayashi H, Kawamoto S, Saga T, Sato N, Hiraga A, Ishimori T, et al. Novel liver macromolecular MR contrast agent with a polypropylenimine diaminobutyl dendrimer core: comparison to the vascular MR contrast agent with the polyamidoamine dendrimer core. Magn Reson Med. 2001b;46(4):795–802.
Kobayashi H, Kawamoto S, Jo SK, Bryant Jr HL, Brechbiel MW, Star RA. Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores. Bioconjug Chem. 2003;14(2):388–94. doi:10.1021/bc025633c.
Kobayashi H, Koyama Y, Barrett T, Hama Y, Regino CA, Shin IS, et al. Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. ACS Nano. 2007;1(4):258–64. doi:10.1021/nn700062z.
Kobayashi H, Longmire MR, Ogawa M, Choyke PL, Kawamoto S. Multiplexed imaging in cancer diagnosis: applications and future advances. Lancet Oncol. 2010a;11(6):589–95. doi:10.1016/S1470-2045(10)70009-7.
Kobayashi H, Ogawa M, Alford R, Choyke PL, Urano Y. New strategies for fluorescent probe design in medical diagnostic imaging. Chem Rev. 2010b;110(5):2620–40. doi:10.1021/cr900263j.
Kobayashi H, Longmire MR, Ogawa M, Choyke PL. Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals. Chem Soc Rev. 2011;40(9):4626–48. doi:10.1039/c1cs15077d.
Kojima C, Turkbey B, Ogawa M, Bernardo M, Regino CA, Bryant Jr LH, et al. Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics. Nanomedicine. 2011;7(6):1001–8. doi:10.1016/j.nano.2011.03.007.
Kok MB, Hak S, Mulder WJ, van der Schaft DW, Strijkers GJ, Nicolay K. Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity. Magn Reson Med. 2009;61(5):1022–32. doi:10.1002/mrm.21910.
Kok MB, de Vries A, Abdurrachim D, Prompers JJ, Grull H, Nicolay K, et al. Quantitative (1)H MRI, (19)F MRI, and (19)F MRS of cell-internalized perfluorocarbon paramagnetic nanoparticles. Contrast Media Mol Imaging. 2011;6(1):19–27. doi:10.1002/cmmi.398.
Langereis S, de Lussanet QG, van Genderen MH, Meijer EW, Beets-Tan RG, Griffioen AW, et al. Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging. NMR Biomed. 2006;19(1):133–41. doi:10.1002/nbm.1015.
Langereis S, Geelen T, Grull H, Strijkers GJ, Nicolay K. Paramagnetic liposomes for molecular MRI and MRI-guided drug delivery. NMR Biomed. 2013;26(7):728–44. doi:10.1002/nbm.2971.
Langereis S, Hijnen N, Strijkers G, Nicolay K, Grull H. Multifunctional liposomes for MRI and image-guided drug delivery. Ther Deliv. 2014;5(1):21–4. doi:10.4155/tde.13.128.
Li K, Wen S, Larson AC, Shen M, Zhang Z, Chen Q, et al. Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer. Int J Nanomedicine. 2013;8:2589–600. doi:10.2147/IJN.S46177.
Li X, Anton N, Zuber G, Vandamme T. Contrast agents for preclinical targeted X-ray imaging. Adv Drug Deliv Rev. 2014;76:116–33. doi:10.1016/j.addr.2014.07.013.
Licha K, Resch-Genger U. Probes for optical imaging: new developments. Drug Discov Today Technol. 2011;8(2–4):e87–94. doi:10.1016/j.ddtec.2011.11.003.
Liu H, Xu Y, Wen S, Chen Q, Zheng L, Shen M, et al. Targeted tumor computed tomography imaging using low-generation dendrimer-stabilized gold nanoparticles. Chemistry. 2013;19(20):6409–16. doi:10.1002/chem.201204612.
Liu H, Wang H, Xu Y, Shen M, Zhao J, Zhang G, et al. Synthesis of PEGylated low generation dendrimer-entrapped gold nanoparticles for CT imaging applications. Nanoscale. 2014;6(9):4521–6. doi:10.1039/c3nr06694k.
Longmire M, Choyke PL, Kobayashi H. Dendrimer-based contrast agents for molecular imaging. Curr Top Med Chem. 2008;8(14):1180–6.
Longmire MR, Ogawa M, Choyke PL, Kobayashi H. Biologically optimized nanosized molecules and particles: more than just size. Bioconjug Chem. 2011;22(6):993–1000. doi:10.1021/bc200111p.
Longmire MR, Ogawa M, Choyke PL, Kobayashi H. Dendrimers as high relaxivity MR contrast agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014;6(2):155–62. doi:10.1002/wnan.1250.
Loudos G, Kagadis GC, Psimadas D. Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles. Eur J Radiol. 2011;78(2):287–95. doi:10.1016/j.ejrad.2010.06.025.
Maeda H. Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug Chem. 2010;21(5):797–802. doi:10.1021/bc100070g.
Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71–9. doi:10.1016/j.addr.2012.10.002.
Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, et al. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release. 2000;65(1–2):133–48.
Menjoge AR, Kannan RM, Tomalia DA. Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today. 2010;15(5–6):171–85. doi:10.1016/j.drudis.2010.01.009.
Mintzer MA, Grinstaff MW. Biomedical applications of dendrimers: a tutorial. Chem Soc Rev. 2011;40(1):173–90. doi:10.1039/b901839p.
Mulder WJ, Strijkers GJ, van Tilborg GA, Griffioen AW, Nicolay K. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed. 2006;19(1):142–64. doi:10.1002/nbm.1011.
Mulder WJ, Strijkers GJ, van Tilborg GA, Cormode DP, Fayad ZA, Nicolay K. Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging. Acc Chem Res. 2009;42(7):904–14. doi:10.1021/ar800223c.
Mulder WJ, McMahon MT, Nicolay K. The evolution of MRI probes: from the initial development to state-of-the-art applications. NMR Biomed. 2013;26(7):725–7. doi:10.1002/nbm.2976.
Nicolay K, Strijkers G, Grüll H. Gd-containing nanoparticles as MRI contrast agents. In: The chemistry of contrast agents in medical magnetic resonance imaging. Hoboken: John Wiley & Sons, Ltd; 2013. p. 449–87.
Ogawa M, Regino CA, Marcelino B, Williams M, Kosaka N, Bryant Jr LH, et al. New nanosized biocompatible MR contrast agents based on lysine-dendri-graft macromolecules. Bioconjug Chem. 2010;21(5):955–60. doi:10.1021/bc9005442.
Opina AC, Wong KJ, Griffiths GL, Turkbey BI, Bernardo M, Nakajima T, et al. Preparation and long-term biodistribution studies of a PAMAM dendrimer G5-Gd-BnDOTA conjugate for lymphatic imaging. Nanomedicine (Lond). 2015;10(9):1423–37. doi:10.2217/nnm.14.113.
Pikkemaat JA, Wegh RT, Lamerichs R, van de Molengraaf RA, Langereis S, Burdinski D, et al. Dendritic PARACEST contrast agents for magnetic resonance imaging. Contrast Media Mol Imaging. 2007;2(5):229–39. doi:10.1002/cmmi.149.
Prabhu RH, Patravale VB, Joshi MD. Polymeric nanoparticles for targeted treatment in oncology: current insights. Int J Nanomedicine. 2015;10:1001–18. doi:10.2147/IJN.S56932.
Rosenblum LT, Kosaka N, Mitsunaga M, Choyke PL, Kobayashi H. In vivo molecular imaging using nanomaterials: general in vivo characteristics of nano-sized reagents and applications for cancer diagnosis (Review). Mol Membr Biol. 2010;27(7):274–85. doi:10.3109/09687688.2010.481640.
Sato N, Kobayashi H, Saga T, Nakamoto Y, Ishimori T, Togashi K, et al. Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice. Clin Cancer Res. 2001;7(11):3606–12.
Sherry AD, Caravan P, Lenkinski RE. Primer on gadolinium chemistry. J Magn Reson Imaging. 2009;30(6):1240–8. doi:10.1002/jmri.21966.
Strijkers GJ, Mulder WJ, van Tilborg GA, Nicolay K. MRI contrast agents: current status and future perspectives. Anticancer Agents Med Chem. 2007;7(3):291–305.
Strijkers GJ, Hak S, Kok MB, Springer Jr CS, Nicolay K. Three-compartment T1 relaxation model for intracellular paramagnetic contrast agents. Magn Reson Med. 2009;61(5):1049–58. doi:10.1002/mrm.21919.
Tack F, Bakker A, Maes S, Dekeyser N, Bruining M, Elissen-Roman C, et al. Modified poly(propylene imine) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes). J Drug Target. 2006;14(2):69–86. doi:10.1080/10611860600635665.
Talanov VS, Regino CAS, Kobayashi H, Bernardo M, Choyke PL, Brechbiel MW. Dendrimer-based nanoprobe for dual modality magnetic resonance and fluorescence imaging. Nano Lett. 2006;6(7):1459–63. doi:10.1021/nl060765q.
van Rooij T, Daeichin V, Skachkov I, de Jong N, Kooiman K. Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy. Int J Hyperthermia. 2015;31(2):90–106. doi:10.3109/02656736.2014.997809.
Wang H, Zheng L, Guo R, Peng C, Shen M, Shi X, et al. Dendrimer-entrapped gold nanoparticles as potential CT contrast agents for blood pool imaging. Nanoscale Res Lett. 2012;7:190. doi:10.1186/1556-276X-7-190.
Wehrl HF, Sauter AW, Divine MR, Pichler BJ. Combined PET/MR: a technology becomes mature. J Nucl Med. 2015;56(2):165–8. doi:10.2967/jnumed.114.150318.
Wen S, Li K, Cai H, Chen Q, Shen M, Huang Y, et al. Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications. Biomaterials. 2013;34(5):1570–80. doi:10.1016/j.biomaterials.2012.11.010.
Wen Q, Wan S, Liu Z, Xu S, Wang H, Yang B. Ultrasound contrast agents and ultrasound molecular imaging. J Nanosci Nanotechnol. 2014;14(1):190–209.
Wu LP, Ficker M, Christensen JB, Trohopoulos PN, Moghimi SM. Dendrimers in medicine: therapeutic concepts and pharmaceutical challenges. Bioconjug Chem. 2015;26(7):1198–211. doi:10.1021/acs.bioconjchem.5b00031.
Yang J, Luo Y, Xu Y, Li J, Zhang Z, Wang H, et al. Conjugation of iron oxide nanoparticles with RGD-modified dendrimers for targeted tumor MR imaging. ACS Appl Mater Interfaces. 2015;7(9):5420–8. doi:10.1021/am508983n.
Yu YB. Fluorinated dendrimers as imaging agents for F-19 MRI. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013;5(6):646–61. doi:10.1002/wnan.1239.
Zhang MG, Guo R, Keri M, Banyai I, Zheng Y, Cao M, et al. Impact of dendrimer surface functional groups on the release of doxorubicin from dendrimer carriers. J Phys Chem B. 2014;118(6):1696–706. doi:10.1021/jp411669k.
Acknowledgements
The work in the authors’ laboratory related to the topic of the chapter was financially supported by the BSIK project entitled Molecular Imaging of Ischemic Heart Disease (project number BSIK03033), the European Union Network of Excellence Diagnostic Molecular Imaging (DIMI, LSHB-CT-2005-512146), the Netherlands Technology Foundation STW (VIDI grant GJS; grant number 07952), the Center for Translational Molecular Medicine (CTMM) projects VOLTA and PARISk and the Netherlands Heart Foundation programme grant (grant number 2006 T106) and was partly performed in the framework of the European Cooperation in Science and Technology (COST) Actions D38 “Metal-Based Systems for Molecular Imaging Applications” and TD1004 “Theragnostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging-Guided Drug Delivery”. The Intramural Research Program of the National Institutes of Health, National Cancer Institute, Centre for Cancer Research, supported H. K.
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Jacobs, I., Strijkers, G.J., Keizer, H.M., Janssen, H.M., Kobayashi, H., Nicolay, K. (2017). Concepts in Diagnostic Probe Design. In: Kiessling, F., Pichler, B., Hauff, P. (eds) Small Animal Imaging. Springer, Cham. https://doi.org/10.1007/978-3-319-42202-2_11
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