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Quantitative Drug Target Imaging Using Paired-Agent Principles

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Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Molecular imaging is often proposed to provide a direct measure of drug targets; however, physiological effects of imaging-agent delivery rates and nonspecific retention can obfuscate the relationship between imaging-agent distribution and the biological distribution of the targeted biomolecule. Coadministration of a suitable control imaging-agent (“nontargeted” version of the targeted agent) simultaneously with a targeted imaging-agent offers a promising solution to account for the nonspecific effects in single-agent molecular imaging and can provide quantitative measures of drug target distribution and availability. This chapter provides an overview of these “paired-agent” molecular imaging protocols with thorough descriptions of how to extract estimates of drug target concentration from paired-agent data under a number of conditions: topical and systemic delivery, and imaging of intravascular, extracellular, and intracellular drug targets.

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References

  1. DiMasi JA, Reichert JM, Feldman L, Malins A (2013) Clinical approval success rates for investigational cancer drugs. Clin Pharmacol Ther 94(3):329–335. https://doi.org/10.1038/clpt.2013.117

    Article  CAS  PubMed  Google Scholar 

  2. Longley DB, Johnston PG (2005) Molecular mechanisms of drug resistance. J Pathol 205(2):275–292. https://doi.org/10.1002/path.1706

    Article  CAS  PubMed  Google Scholar 

  3. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63(3):136–151. https://doi.org/10.1016/j.addr.2010.04.009

    Article  CAS  PubMed  Google Scholar 

  4. Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2(2):123–131. https://doi.org/10.1038/nrd1007

    Article  CAS  PubMed  Google Scholar 

  5. Gross S, Piwnica-Worms D (2006) Molecular imaging strategies for drug discovery and development. Curr Opin Chem Biol 10(4):334–342. https://doi.org/10.1016/j.cbpa.2006.06.028

    Article  CAS  PubMed  Google Scholar 

  6. Hargreaves RJ (2008) The role of molecular imaging in drug discovery and development. Clin Pharmacol Ther 83(2):349–353. https://doi.org/10.1038/sj.clpt.6100467

    Article  CAS  PubMed  Google Scholar 

  7. Vinegoni C, Fumene Feruglio P, Brand C, Lee S, Nibbs AE, Stapleton S, Shah S, Gryczynski I, Reiner T, Mazitschek R, Weissleder R (2017) Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging. Nat Protoc 12(7):1472–1497. https://doi.org/10.1038/nprot.2017.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dubach JM, Vinegoni C, Mazitschek R, Fumene Feruglio P, Cameron LA, Weissleder R (2014) In vivo imaging of specific drug-target binding at subcellular resolution. Nat Commun 5:3946. https://doi.org/10.1038/ncomms4946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Orcutt KD, Adams GP, Wu AM, Silva MD, Harwell C, Hoppin J, Matsumura M, Kotsuma M, Greenberg J, Scott AM, Beckman RA (2017) Molecular simulation of receptor occupancy and tumor penetration of an antibody and smaller scaffolds: application to molecular imaging. Mol Imaging Biol 19(5):656–664. https://doi.org/10.1007/s11307-016-1041-y

    Article  CAS  PubMed  Google Scholar 

  10. Herschman HR (2003) Molecular imaging: looking at problems, seeing solutions. Science 302(5645):605–608. https://doi.org/10.1126/science.1090585

    Article  CAS  PubMed  Google Scholar 

  11. Matthews PM, Rabiner EA, Passchier J, Gunn RN (2012) Positron emission tomography molecular imaging for drug development. Br J Clin Pharmacol 73(2):175–186. https://doi.org/10.1111/j.1365-2125.2011.04085.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17(5):545–580. https://doi.org/10.1101/gad.1047403.

    Article  CAS  PubMed  Google Scholar 

  13. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7(4):493–496. https://doi.org/10.1038/86573

    Article  CAS  PubMed  Google Scholar 

  14. Tichauer KM, Wang Y, Pogue BW, Liu JT (2015) Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging. Phys Med Biol 60(14):R239–R269. https://doi.org/10.1088/0031-9155/60/14/R239

    Article  PubMed  PubMed Central  Google Scholar 

  15. Xu X, Wang Y, Xiang J, Liu JTC, Tichauer KM (2017) Rinsing paired-agent model (RPAM) to quantify cell-surface receptor concentrations in topical staining applications of thick tissues. Phys Med Biol 62(12):5098–5113. https://doi.org/10.1088/1361-6560/aa6cf1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kang S, Wang YW, Xu X, Navarro E, Tichauer KM, Liu JTC (2018) Microscopic investigation of topically applied nanoparticles for molecular imaging of fresh tissue surfaces. J Biophotonics 11(4):e201700246. https://doi.org/10.1002/jbio.201700246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu JT, Helms MW, Mandella MJ, Crawford JM, Kino GS, Contag CH (2009) Quantifying cell-surface biomarker expression in thick tissues with ratiometric three-dimensional microscopy. Biophys J 96(6):2405–2414. https://doi.org/10.1016/j.bpj.2008.12.3908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Davis SC, Gibbs SL, Gunn JR, Pogue BW (2013) Topical dual-stain difference imaging for rapid intra-operative tumor identification in fresh specimens. Opt Lett 38(23):5184–5187. https://doi.org/10.1364/OL.38.005184

    Article  PubMed  PubMed Central  Google Scholar 

  19. Korber J, Barth C, Gibbs S (2018) Nile red derivatives enable improved ratiometric imaging for nerve-specific contrast. J Biomed Opt 23(7):1–13. https://doi.org/10.1117/1.JBO.23.7.076002.

    Article  PubMed  Google Scholar 

  20. Zalutsky MR, Garg PK, Friedman HS, Bigner DD (1989) Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity. Proc Natl Acad Sci U S A 86(18):7149–7153. https://doi.org/10.1073/pnas.86.18.7149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Baeten J, Haller J, Shih H, Ntziachristos V (2009) In vivo investigation of breast cancer progression by use of an internal control. Neoplasia 11(3):220–227. https://doi.org/10.1593/neo.08648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tichauer KM, Samkoe KS, Sexton KJ, Hextrum SK, Yang HH, Klubben WS, Gunn JR, Hasan T, Pogue BW (2012) In vivo quantification of tumor receptor binding potential with dual-reporter molecular imaging. Mol Imaging Biol 14(5):584–592. https://doi.org/10.1007/s11307-011-0534-y

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zalutsky MR, Moseley RP, Coakham HB, Coleman RE, Bigner DD (1989) Pharmacokinetics and tumor localization of 131I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies. Cancer Res 49(10):2807–2813

    CAS  PubMed  Google Scholar 

  24. Wu AM (2014) Engineered antibodies for molecular imaging of cancer. Methods 65(1):139–147. https://doi.org/10.1016/j.ymeth.2013.09.015

    Article  CAS  PubMed  Google Scholar 

  25. Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23(9):1137–1146. https://doi.org/10.1038/nbt1141

    Article  CAS  PubMed  Google Scholar 

  26. Lee S, Xie J, Chen X (2010) Peptide-based probes for targeted molecular imaging. Biochemistry 49(7):1364–1376. https://doi.org/10.1021/bi901135x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Weissleder R (2006) Molecular imaging in cancer. Science 312(5777):1168–1171. https://doi.org/10.1126/science.1125949

    Article  CAS  PubMed  Google Scholar 

  28. Berman DS, Kiat H, Friedman JD, Wang FP, van Train K, Matzer L, Maddahi J, Germano G (1993) Separate acquisition rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: a clinical validation study. J Am Coll Cardiol 22(5):1455–1464. https://doi.org/10.1016/0735-1097(93)90557-h

    Article  CAS  PubMed  Google Scholar 

  29. Bourdon MA, Coleman RE, Blasberg RG, Groothuis DR, Bigner DD (1984) Monoclonal antibody localization in subcutaneous and intracranial human glioma xenografts: paired-label and imaging analysis. Anticancer Res 4(3):133–140

    CAS  PubMed  Google Scholar 

  30. Wang YW, Khan A, Som M, Wang D, Chen Y, Leigh SY, Meza D, McVeigh PZ, Wilson BC, Liu JT (2014) Rapid ratiometric biomarker detection with topically applied SERS nanoparticles. Technology (Singap World Sci) 2(2):118–132. https://doi.org/10.1142/S2339547814500125

    Article  Google Scholar 

  31. Pogue BW, Samkoe KS, Hextrum S, O'Hara JA, Jermyn M, Srinivasan S, Hasan T (2010) Imaging targeted-agent binding in vivo with two probes. J Biomed Opt 15(3):030513. https://doi.org/10.1117/1.3449109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pian Q, Yao R, Sinsuebphon N, Intes X (2017) Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging. Nat Photonics 11:411–414. https://doi.org/10.1038/NPHOTON.2017.82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gilad AA, van Laarhoven HW, McMahon MT, Walczak P, Heerschap A, Neeman M, van Zijl PC, Bulte JW (2009) Feasibility of concurrent dual contrast enhancement using CEST contrast agents and superparamagnetic iron oxide particles. Magn Reson Med 61(4):970–974. https://doi.org/10.1002/mrm.21928

    Article  PubMed  PubMed Central  Google Scholar 

  34. Andreyev A, Celler A (2011) Dual-isotope PET using positron-gamma emitters. Phys Med Biol 56(14):4539–4556. Epub 2011/07/01. https://doi.org/10.1088/0031-9155/56/14/020

    Article  CAS  PubMed  Google Scholar 

  35. Ntziachristos V, Razansky D (2010) Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem Rev 110(5):2783–2794. https://doi.org/10.1021/cr9002566

    Article  CAS  PubMed  Google Scholar 

  36. Giesen C, Wang HA, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B, Schüffler PJ, Grolimund D, Buhmann JM, Brandt S, Varga Z, Wild PJ, Günther D, Bodenmiller B (2014) Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat Methods 11(4):417–422. https://doi.org/10.1038/nmeth.2869

    Article  CAS  PubMed  Google Scholar 

  37. Angelo M, Bendall SC, Finck R, Hale MB, Hitzman C, Borowsky AD, Levenson RM, Lowe JB, Liu SD, Zhao S, Natkunam Y, Nolan GP (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20(4):436–442. https://doi.org/10.1038/nm.3488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Aime S, Battista Giovenzana G, Terreno E (2010) Chemistry of molecular imaging: an overview. In: Weissleder R, Ross BD, Rehemtulla A, Gambhir SS (eds) Molecular imaging: principles and practice. People's Medical Publishing House-USA, Shelton, CT, pp 277–303

    Google Scholar 

  39. Choi HS, Nasr K, Alyabyev S, Feith D, Lee JH, Kim SH, Ashitate Y, Hyun H, Patonay G, Strekowski L, Henary M, Frangioni JV (2011) Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angew Chem Int Ed Engl 50(28):6258–6263. https://doi.org/10.1002/anie.201102459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Thurber GM, Schmidt MM, Wittrup KD (2008) Factors determining antibody distribution in tumors. Trends Pharmacol Sci 29(2):57–61. https://doi.org/10.1016/j.tips.2007.11.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lammertsma AA, Bench CJ, Hume SP, Osman S, Gunn K, Brooks DJ, Frackowiak RS (1996) Comparison of methods for analysis of clinical [11C]raclopride studies. J Cereb Blood Flow Metab 16(1):42–52. https://doi.org/10.1097/00004647-199601000-00005

    Article  CAS  PubMed  Google Scholar 

  42. Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. NeuroImage 4(3 Pt 1):153–158. https://doi.org/10.1006/nimg.1996.0066.

    Article  CAS  PubMed  Google Scholar 

  43. Hume SP, Myers R, Bloomfield PM, Opacka-Juffry J, Cremer JE, Ahier RG, Luthra SK, Brooks DJ, Lammertsma AA (1992) Quantitation of carbon-11-labeled raclopride in rat striatum using positron emission tomography. Synapse 12(1):47–54. https://doi.org/10.1002/syn.890120106

    Article  CAS  PubMed  Google Scholar 

  44. Hamzei N, Samkoe KS, Elliott JT, Holt RW, Gunn JR, Hasan T, Pogue BW, Tichauer KM (2014) Comparison of kinetic models for dual-tracer receptor concentration imaging in tumors. Austin J Biomed Eng 1(1)

    Google Scholar 

  45. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27(9):1533–1539. https://doi.org/10.1038/sj.jcbfm.9600493

    Article  CAS  PubMed  Google Scholar 

  46. Li C, Xu X, McMahon N, Alhaj Ibrahim O, Sattar HA, Tichauer KM (2019) Paired-agent fluorescence molecular imaging of sentinel lymph nodes using indocyanine green as a control agent for antibody-based targeted agents. Contrast Media Mol Imaging 2019:7561862. https://doi.org/10.1155/2019/7561862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Davis SC, Samkoe KS, Tichauer KM, Sexton KJ, Gunn JR, Deharvengt SJ, Hasan T, Pogue BW (2013) Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo. Proc Natl Acad Sci U S A 110(22):9025–9030. https://doi.org/10.1073/pnas.1213490110

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kanick SC, Tichauer KM, Gunn J, Samkoe KS, Pogue BW (2014) Pixel-based absorption correction for dual-tracer fluorescence imaging of receptor binding potential. Biomedical optics express 5(10):3280–3291. https://doi.org/10.1364/boe.5.003280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim A, Khurana M, Moriyama Y, Wilson BC (2010) Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements. J Biomed Opt 15(6):067006. https://doi.org/10.1117/1.3523616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sadeghipour N, Davis SC, Tichauer KM (2018) Correcting for targeted and control agent signal differences in paired-agent molecular imaging of cancer cell-surface receptors. J Biomed Opt 23(6):1–11. https://doi.org/10.1117/1.JBO.23.6.066004

    Article  PubMed  Google Scholar 

  51. PRESSMAN D, DAY ED, BLAU M (1957) The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res 17(9):845–850

    CAS  PubMed  Google Scholar 

  52. Tichauer KM, Samkoe KS, Sexton KJ, Gunn JR, Hasan T, Pogue BW (2012) Improved tumor contrast achieved by single time point dual-reporter fluorescence imaging. J Biomed Opt 17(6):066001. https://doi.org/10.1117/1.JBO.17.6.066001

    Article  PubMed  PubMed Central  Google Scholar 

  53. Sinha L, Wang Y, Yang C, Khan A, Brankov JG, Liu JT, Tichauer KM (2015) Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles. Sci Rep 5:8582. https://doi.org/10.1038/srep08582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kang S, Xu X, Navarro E, Wang Y, Liu JTC, Tichauer KM (2019) Modeling the binding and diffusion of receptor-targeted nanoparticles topically applied on fresh tissue specimens. Phys Med Biol 64(4):045013. https://doi.org/10.1088/1361-6560/aaff81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sadeghipour N, Davis SC, Tichauer KM (2017) Generalized paired-agent kinetic model for in vivo quantification of cancer cell-surface receptors under receptor saturation conditions. Phys Med Biol 62(2):394–414. https://doi.org/10.1088/1361-6560/62/2/394

    Article  CAS  PubMed  Google Scholar 

  56. Tichauer KM, Deharvengt SJ, Samkoe KS, Gunn JR, Bosenberg MW, Turk MJ, Hasan T, Stan RV, Pogue BW (2014) Tumor endothelial marker imaging in melanomas using dual-tracer fluorescence molecular imaging. Mol Imaging Biol 16(3):372–382. https://doi.org/10.1007/s11307-013-0692-1

    Article  PubMed  Google Scholar 

  57. Tichauer KM, Diop M, Elliott JT, Samkoe KS, Hasan T, St Lawrence K, Pogue BW (2014) Accounting for pharmacokinetic differences in dual-tracer receptor density imaging. Phys Med Biol 59(10):2341–2351. https://doi.org/10.1088/0031-9155/59/10/2341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gunn RN, Gunn SR, Cunningham VJ (2001) Positron emission tomography compartmental models. J Cereb Blood Flow Metab 21(6):635–652. https://doi.org/10.1097/00004647-200106000-00002

    Article  CAS  PubMed  Google Scholar 

  59. Cilliers C, Guo H, Liao J, Christodolu N, Thurber GM (2016) Multiscale modeling of antibody-drug conjugates: connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy. AAPS J 18(5):1117–1130. https://doi.org/10.1208/s12248-016-9940-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bhatnagar S, Deschenes E, Liao J, Cilliers C, Thurber GM (2014) Multichannel imaging to quantify four classes of pharmacokinetic distribution in tumors. J Pharm Sci 103(10):3276–3286. https://doi.org/10.1002/jps.24086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tzafriri AR, Lerner EI, Flashner-Barak M, Hinchcliffe M, Ratner E, Parnas H (2005) Mathematical modeling and optimization of drug delivery from intratumorally injected microspheres. Clin Cancer Res 11(2 Pt 1):826–834

    CAS  PubMed  Google Scholar 

  62. Bäckman P, Arora S, Couet W, Forbes B, de Kruijf W, Paudel A (2018) Advances in experimental and mechanistic computational models to understand pulmonary exposure to inhaled drugs. Eur J Pharm Sci 113:41–52. https://doi.org/10.1016/j.ejps.2017.10.030

    Article  CAS  PubMed  Google Scholar 

  63. Holm R, Hoest J (2004) Successful in silico predicting of intestinal lymphatic transfer. Int J Pharm 272(1–2):189–193. https://doi.org/10.1016/j.ijpharm.2003.12.017

    Article  CAS  PubMed  Google Scholar 

  64. Winner KK, Steinkamp MP, Lee RJ, Swat M, Muller CY, Moses ME, Jiang Y, Wilson BS (2016) Spatial modeling of drug delivery routes for treatment of disseminated ovarian cancer. Cancer Res 76(6):1320–1334. https://doi.org/10.1158/0008-5472.CAN-15-1620

    Article  CAS  PubMed  Google Scholar 

  65. Kuttler A, Dimke T, Kern S, Helmlinger G, Stanski D, Finelli LA (2010) Understanding pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug distribution within the CSF space for intrathecal drugs. J Pharmacokinet Pharmacodyn 37(6):629–644. https://doi.org/10.1007/s10928-010-9184-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Slobbe P (2016) Radiolabeled tyrosine kinase inhibitors for drug development and cancer treatment: TKI-PET

    Google Scholar 

  67. Huang SC, Bahn MM, Barrio JR, Hoffman JM, Satyamurthy N, Hawkins RA, Mazziotta JC, Phelps ME (1989) A double-injection technique for in vivo measurement of dopamine D2-receptor density in monkeys with 3-(2′-[18F]fluoroethyl)spiperone and dynamic positron emission tomography. J Cereb Blood Flow Metab 9(6):850–858. https://doi.org/10.1038/jcbfm.1989.119

    Article  CAS  PubMed  Google Scholar 

  68. Delforge J, Pappata S, Millet P, Samson Y, Bendriem B, Jobert A, Crouzel C, Syrota A (1995) Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol. J Cereb Blood Flow Metab 15(2):284–300. https://doi.org/10.1038/jcbfm.1995.34

    Article  CAS  PubMed  Google Scholar 

  69. Herman P, Maliwal BP, Lakowicz JR (2002) Real-time background suppression during frequency domain lifetime measurements. Anal Biochem 309(1):19–26. https://doi.org/10.1016/s0003-2697(02)00213-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Davis SC, Pogue BW, Springett R, Leussler C, Mazurkewitz P, Tuttle SB, Gibbs-Strauss SL, Jiang SS, Dehghani H, Paulsen KD (2008) Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue. Rev Sci Instrum 79(6):064302. https://doi.org/10.1063/1.2919131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA

    Kenneth M. Tichauer

  2. Molecular Imaging Program, Stanford University, Stanford, CA, USA

    Negar Sadeghipour

  3. Department of Mechanical Engineering, University of Washington, Seattle, WA, USA

    Yu “ Winston” Wang & Jonathan T. C. Liu

  4. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA

    Summer L. Gibbs

  5. Thayer School of Engineering, Dartmouth University, Hanover, NH, USA

    Kimberley S. Samkoe

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  1. Kenneth M. Tichauer
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  2. Negar Sadeghipour
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  3. Yu “ Winston” Wang
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  4. Summer L. Gibbs
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  5. Jonathan T. C. Liu
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  6. Kimberley S. Samkoe
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Correspondence to Kenneth M. Tichauer .

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Editors and Affiliations

  1. College of Pharmacy, University of Michigan, Ann Arbor, MI, USA

    Gus R. Rosania

  2. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Greg M. Thurber

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Tichauer, K.M., Sadeghipour, N., Wang, Y.“.W., Gibbs, S.L., Liu, J.T.C., Samkoe, K.S. (2021). Quantitative Drug Target Imaging Using Paired-Agent Principles. In: Rosania, G.R., Thurber, G.M. (eds) Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1250-7_13

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