Molecular Imaging and Biology

, Volume 19, Issue 3, pp 348–356 | Cite as

Advancing Drug Discovery and Development Using Molecular Imaging (ADDMI): an Interest Group of the World Molecular Imaging Society and an Inaugural Session on Positron Emission Tomography (PET)

  • Shil Patel
  • Karl Schmidt
  • Jacob Hesterman
  • Jack Hoppin
Special Topic


Multi-modality molecular imaging techniques have expanded the role of imaging biomarkers in the pharmaceutical industry and are beginning to streamline the drug discovery and development process. The World Molecular Imaging Society (WMIS) serves as a forum for discussing innovative and exploratory multi-modal, interdisciplinary molecular imaging research with a mission of bridging the gap between pathology and in vivo imaging. To formalize the role of the WMIS in pharmaceutical research efforts, members of the society have formed an interest group entitled Advancing Drug Discovery and Development using Molecular Imaging (ADDMI). The ADDMI interest group launched their efforts at the 2016 World Molecular Imaging Congress by hosting a session of invited lectures on translational positron emission tomography (PET) imaging in the central nervous system. This article provides a synopsis of those lectures and frames the role of translational imaging biomarker strategies in the drug discovery and development process.

Key words

Molecular imaging Drug research and development Positron emission tomography Imaging biomarkers 


Compliance with Ethical Standards

Conflict of Interest

The authors are full time employees of their respective companies as stated in the author details.


  1. 1.
    Zerhouni E (2003) The NIH roadmap. Science 302:63–72CrossRefPubMedGoogle Scholar
  2. 2.
    Avorn J (2015) The $2.6 billion pill—methodologic and policy considerations. N Engl J Med 372:1877–1879CrossRefPubMedGoogle Scholar
  3. 3.
    Mullin, R. (2014) Tufts study finds big rise in cost of drug development. Chem Eng News Nov 20 (ISSN 0009-2347)Google Scholar
  4. 4.
    Kaitin KI, DiMasi JA (2011) Pharmaceutical Innovation in the 21st century: new drug approvals in the first decade, 2000–2009. Nature 89:183–188Google Scholar
  5. 5.
    Petrova E (2014) Innovation in the pharmaceutical industry: the process of drug discovery and development. In: Ding M et al (eds) Innovation and marketing in the pharmaceutical industry. Springer Science+Business Media, New York, pp 19–81CrossRefGoogle Scholar
  6. 6.
    Hargreaves RJ, Hoppin J, Sevigney J et al (2015) Optimizing central nervous system drug development using molecular imaging. Clin Pharm Ther 98:47–60CrossRefGoogle Scholar
  7. 7.
    James ML, Gambhir SS (2012) A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev 92:897–965CrossRefPubMedGoogle Scholar
  8. 8.
    Hoppin J, Davis KO, Hesterman J et al (2011) Assessing antibody pharmacokinetics in mice with in vivo imaging. J Pharm Exp Ther 337:350–358CrossRefGoogle Scholar
  9. 9.
    Cuhna L, Szigeti K, Mathe D, Metello LF (2014) The role of molecular imaging in modern drug development. Drug Discov Today 19:936–948CrossRefGoogle Scholar
  10. 10.
    De Vries EGE, de Jong S, Gietema JA (2015) Molecular imaging as a tool for drug development and trial design. J Clin Onco 33:2585–2587CrossRefGoogle Scholar
  11. 11.
    Buckler AJ, Bresolin L, Dunnick NR et al (2011) A collaborative enterprise for multi-stakeholder participation in the advancement of quantitative imaging. Radiology 258:906–914CrossRefPubMedGoogle Scholar
  12. 12.
    Frank R, Hargreaves R (2003) Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov 2:566–580CrossRefPubMedGoogle Scholar
  13. 13.
    Hargreaves R, Wagner J (2006) Imaging as a biomarker for decision making in drug development. In: Beckmann N (ed) In-vivo MR techniques in drug discovery and development. Taylor and Francis, New York, pp 31–46CrossRefGoogle Scholar
  14. 14.
    Hargreaves RJ (2008) The role of molecular imaging in drug discovery and development. Clin Pharmacol Ther 83:349–353CrossRefPubMedGoogle Scholar
  15. 15.
    Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2:123–131CrossRefPubMedGoogle Scholar
  16. 16.
    Nordberg A (2011) Molecular imaging in Alzheimer’s disease: new perspectives on biomarkers for early diagnosis and drug development. Alz Res Therapy 3:34–43CrossRefGoogle Scholar
  17. 17.
    Grachev ID, Hargreaves RJ (2010) Integrative process: neuroscience clinical imaging biomarkers. In: Borsook D et al (eds) Imaging in CNS drug discovery and development: implications for disease and therapy. Springer Science+Business Media, New York, pp 363–379CrossRefGoogle Scholar
  18. 18.
    Borsook D, Becerra L, Hargreaves R (2006) A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov 5:411–425CrossRefPubMedGoogle Scholar
  19. 19.
    Young AB (2009) Four decades of neurodegenerative disease research: how far we have come! J Neurosci 29:12722–12728CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Patel S, Gibson R (2008) In vivo site-directed radiotracers: a mini-review. Nuc Med Biol 35:805–815CrossRefGoogle Scholar
  21. 21.
    Solin O, Eskola O, Hamill T et al (2004) Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ). Mol Imaging Biol 6:373–384CrossRefPubMedGoogle Scholar
  22. 22.
    Bergstrom M, Hargreaves RJ, Burns HD et al (2004) Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55:1007–1012CrossRefPubMedGoogle Scholar
  23. 23.
    Hargreaves R, Ferreira JC, Hughes D et al (2011) Development of aprepitant, the first neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Ann N Y Acad Sci 1222:40–48CrossRefPubMedGoogle Scholar
  24. 24.
    Keller M, Montgomery S, Ball W et al (2006) Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 59(3):216–223CrossRefPubMedGoogle Scholar
  25. 25.
    Herholz K, Ebmeier K (2011) Clinical amyloid imaging in Alzheimer’s disease. Lancet Neurol 10:667–670CrossRefPubMedGoogle Scholar
  26. 26.
    Sevigny J, Suhy J, Chiao P et al (2016) (2016) amyloid PET screening for enrichment of early-stage Alzheimer disease clinical trials: experience in a phase 1b clinical trial. Alzheimer Dis Assoc Disord 30:1–7CrossRefPubMedGoogle Scholar
  27. 27.
    Doody RS, Thomas RG, Fralow M et al (2014) Phase 3 trials of Solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311–321CrossRefPubMedGoogle Scholar
  28. 28.
    Salloway S, Sperling R, Fox NC et al (2014) Two phase 3 trials of Bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 370:322–333CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Sevigny J, Chiao P, Bussiere T et al (2016) The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 537:50–56CrossRefPubMedGoogle Scholar
  30. 30.
    Calcoen D, Elias L, Yu X (2015) What does it take to produce a breakthrough drug? Nat Rev Drug Disc 14:161–162CrossRefGoogle Scholar
  31. 31.
    Walji AM, Hostetler ED, Selnick H et al (2016) Discovery of 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]-MK-6240): a positron emission tomography (PET) imaging agent for quantification of neurofibrillary tangles (NFTs). J Med Chem 59:4778–4789CrossRefPubMedGoogle Scholar
  32. 32.
    Hostetler ED, Walji AM, Zeng Z et al (2016) Preclinical characterization of 18F-MK-6240, a promising PET tracer for in vivo quantification of human neurofibrillary tangles. J Nucl Med 57:1599–1606CrossRefPubMedGoogle Scholar
  33. 33.
    Xia C-F, Artega J, Chen G et al (2013) [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alz Dem 9:666–676CrossRefGoogle Scholar
  34. 34.
    Harada R, Okamura N, Furumoto S et al (2015) 18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer’s disease. J Nucl Med 42:1052–1061CrossRefGoogle Scholar
  35. 35.
    Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42:631–639CrossRefPubMedGoogle Scholar
  36. 36.
    Ganzer S, Arlt S, Schoder V et al (2003) CSF-tau, CSF-Abeta1-42, ApoE-genotype and clinical parameters in the diagnosis of Alzheimer’s disease: combination of CSF-tau and MMSE yields highest sensitivity and specificity. J Neual Transm 110:1149–1160CrossRefGoogle Scholar
  37. 37.
    Rub U, Stratmann K, Heinsen H, et al. (2017) Alzheimer’s disease: characterization of the brain sites of the initial tau cytoskeletal pathology will improve the success of novel immunological anti-tau treatment approaches. J Alz Dis. doi: 10.3233/JAD-161102
  38. 38.
    Yasuno F, Kazui H, Morita N et al (2016) High amyloid-β deposition related to depressive symptoms in older individuals with normal cognition: a pilot study. Int J Geriatr Psych 31:920–928CrossRefGoogle Scholar
  39. 39.
    Jack CR, Knopman DS, Weigand SD et al (2012) An operational approach to National Institute on Aging-Alzheimer’s Association criteria for preclinical Alzheimer disease. Ann Neurol 71:765–775CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Jaber M, Robsinson SW, Missale C, Caron M (1996) Dopamine receptors and brain function. Neurophram 35:1503–1519CrossRefGoogle Scholar
  41. 41.
    Olivier B, Soudijn W, van Wijngaarden I (2000) Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors. Prog Drug Res 54:59–119CrossRefPubMedGoogle Scholar
  42. 42.
    Zhang Z, Wu J, Yu J, Xiao J (2012) A brief review on the evolution of GPCR: conservation and diversification. Open J Genetics 2:11–17CrossRefGoogle Scholar
  43. 43.
    Holzer M, Holzapfel HP, Zedlick D et al (1994) Abnormally phosphorylated tau protein in Alzheimer’s disease: heterogeneity of individual regional distribution and relationship to clinical severity. Neurosci 63:499–516CrossRefGoogle Scholar
  44. 44.
    Safinia C, Bershad EM, Clark HB et al (2016) Chronic traumatic encephalopathy in athletes involved with high-impact sports. J Vasc Interv Neurol 9:34–48PubMedPubMedCentralGoogle Scholar
  45. 45.
    Villegmagne VL, Mulligand RS, Pejoska S et al (2012) Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease. Eur J Nuc Med Mol Imaging 39:983–989CrossRefGoogle Scholar
  46. 46.
    Eckelman WC, Gibson RE (1993) The design of site-directed radiopharmaceuticals for use in drug discovery. In: Burns HD, Gibson RE, Dannals R, Siegl P (eds) Nuclear imaging and drug discovery, development and approval. Birkhauser, Boston, pp 114–134Google Scholar
  47. 47.
    Eckelman WC, Gibson RE, Zeszotarski WJ et al (1979) The design of receptor binding radiotracers. In: Colombetti L (ed) Principles of radiopharmacology. CRC Press, New York, pp 251–274Google Scholar
  48. 48.
    Wilson RM, Danishefsky SJ (2010) On the reach of chemical synthesis: creation of a MiniPipeline from an academic laboratory. Angew Chemie Intl Ed 49:6032–6056CrossRefGoogle Scholar
  49. 49.
    Holland JP, Liang SH, Collier TL et al (2014) Alternative approaches for PET radiotracer development in Alzheimer’s disease: imaging beyond plaque. J Labelled Comp Radiopharm 57:323–331CrossRefPubMedGoogle Scholar
  50. 50.
    Chien DT, Bahri S, Szardenings AK et al (2013) Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J. Alz Dis 34:457–468Google Scholar
  51. 51.
    Xia CF, Arteaga J, Chen G et al (2013) [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alz Dement 9:666–676CrossRefGoogle Scholar
  52. 52.
    Shoup TM, Yokell DL, Rice PA et al (2013) A concise radiosynthesis of the tau radiopharmaceutical, [18F]T807. J Labelled Comp Radiopharm 56:736–740CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Lee C-C, Sui G, Elizarov A, Shu CJ et al (2005) Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science 310:1793–1796CrossRefPubMedGoogle Scholar
  54. 54.
    Liang S, Yokell DL, Normandin MD et al (2014) First human use of a radiopharmaceutical prepared by continuous-flow microfluidic radiofluorination: proof of concept with the tau imaging agent [18F]T807. Mol Imaging 13:1–5Google Scholar

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  1. 1.Eisai AiM InstituteAndoverUSA
  2. 2.CelgeneSummitUSA
  3. 3.inviCRO LLCBostonUSA

Personalised recommendations