Use of Molecular Imaging in Clinical Drug Development: a Systematic Review

  • Hyeomin Son
  • Kyungho Jang
  • Heechan Lee
  • Sang Eun Kim
  • Keon Wook Kang
  • Howard LeeEmail author
Original Article



Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies.


We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted.


Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%).


The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.


Molecular imaging Drug development PET SPECT 



This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1072).

Compliance with Ethical Standards

Conflicts of Interest

Hyeomin Son, Kyungho Jang, Heechan Lee, Sang Eun Kim, Keon Wook Kang, and Howard Lee certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Supplementary material

13139_2019_593_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 27 kb)


  1. 1.
    Mankoff DA. A definition of molecular imaging. J Nucl Med 2007;48:18N, 21N.Google Scholar
  2. 2.
    McDermott S, Kilcoyne A. Molecular imaging-its current role in cancer. QJM. 2016;109:295–9.CrossRefGoogle Scholar
  3. 3.
    Filipiak-Strzecka D, Kowalczyk E, Hamala P, Kot N, Kasprzak JD, Kusmierek J, et al. Long-term prognostic value of inducible and resting perfusion defects detected by single-photon emission computed tomography in the era of wide availability of coronary revascularization. Clin Physiol Funct Imaging. 2013;33:218–23.CrossRefGoogle Scholar
  4. 4.
    Teng FF, Meng X, Sun XD, Yu JM. New strategy for monitoring targeted therapy: molecular imaging. Int J Nanomedicine. 2013;8:3703–13.Google Scholar
  5. 5.
    Oh P, Li Y, Yu J, Durr E, Krasinska KM, Carver LA, et al. Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature. 2004;429:629–35.CrossRefGoogle Scholar
  6. 6.
    Gross S, Piwnica-Worms D. Molecular imaging strategies for drug discovery and development. Curr Opin Chem Biol. 2006;10:334–42.CrossRefGoogle Scholar
  7. 7.
    Rollo FD. Molecular imaging: an overview and clinical applications. Radiol Manage. 2003;25:28–32 quiz 3-5.Google Scholar
  8. 8.
    Shah K, Jacobs A, Breakefield XO, Weissleder R. Molecular imaging of gene therapy for cancer. Gene Ther. 2004;11:1175–87.CrossRefGoogle Scholar
  9. 9.
    Galban CJ, Galban S, Van Dort ME, Luker GD, Bhojani MS, Rehemtulla A, et al. Applications of molecular imaging. Prog Mol Biol Transl Sci. 2010;95:237–98.CrossRefGoogle Scholar
  10. 10.
    Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA. 2005;293:855–62.CrossRefGoogle Scholar
  11. 11.
    DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33.CrossRefGoogle Scholar
  12. 12.
    Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS. Molecular imaging in drug development. Nat Rev Drug Discov. 2008;7:591–607.CrossRefGoogle Scholar
  13. 13.
    Josephs D, Spicer J, O'Doherty M. Molecular imaging in clinical trials. Target Oncol. 2009;4:151–68.CrossRefGoogle Scholar
  14. 14.
    Uppoor RS, Mummaneni P, Cooper E, Pien HH, Sorensen AG, Collins J, et al. The use of imaging in the early development of neuropharmacological drugs: a survey of approved NDAs. Clin Pharmacol Ther. 2008;84:69–74.CrossRefGoogle Scholar
  15. 15.
    Food and Drug Administration of USA. Critical path opportunities initiated during 2006. 2006. Accessed 06 Jan 2018.
  16. 16.
    Pharmaceutical Research and Manufacturers of America (2015) Biopharmaceutical research industry profile. 2015. Accessed 06 Dec 2017.
  17. 17.
    Owonikoko TK, Ramalingam SS, Miller DL, Force SD, Sica GL, Mendel J, et al. A translational, Pharmacodynamic, and pharmacokinetic phase IB clinical study of everolimus in resectable non-small cell lung cancer. Clin Cancer Res. 2015;21:1859–68.CrossRefGoogle Scholar
  18. 18.
    Dimitrakopoulou-Strauss A. PET-based molecular imaging in personalized oncology: potential of the assessment of therapeutic outcome. Future Oncol. 2015;11:1083–91.CrossRefGoogle Scholar
  19. 19.
    Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest. 2003;123:137S–46S.CrossRefGoogle Scholar
  20. 20.
    Tufts Center for the Study of Drug Development. Outlook 2015. 2015. Accessed 08 Jan 2018.
  21. 21.
    Lim KS, Kwon JS, Jang IJ, Jeong JM, Lee JS, Kim HW, et al. Modeling of brain D2 receptor occupancy-plasma concentration relationships with a novel antipsychotic, YKP1358, using serial PET scans in healthy volunteers. Clin Pharmacol Ther. 2007;81:252–8.CrossRefGoogle Scholar
  22. 22.
    Wagner CC, Bauer M, Karch R, Feurstein T, Kopp S, Chiba P, et al. A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET. J Nucl Med. 2009;50:1954–61.CrossRefGoogle Scholar
  23. 23.
    Shah RC, Matthews DC, Andrews RD, Capuano AW, Fleischman DA, VanderLugt JT, et al. An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer’s disease. Curr Alzheimer Res. 2014;11:564–73.CrossRefGoogle Scholar
  24. 24.
    Pimlott SL, Sutherland A. Molecular tracers for the PET and SPECT imaging of disease. Chem Soc Rev. 2011;40:149–62.CrossRefGoogle Scholar
  25. 25.
    Paans AM, van Waarde A, Elsinga PH, Willemsen AT, Vaalburg W. Positron emission tomography: the conceptual idea using a multidisciplinary approach. Methods. 2002;27:195–207.CrossRefGoogle Scholar
  26. 26.
    Miller PW, Long NJ, Vilar R, Gee AD. Synthesis of 11C, 18F, 15O, and 13N radiolabels for positron emission tomography. Angew Chem Int Ed Eng. 2008;47:8998–9033.CrossRefGoogle Scholar
  27. 27.
    Catafau AM, Bullich S, Nucci G, Burgess C, Gray F, Merlo-Pich E, et al. Contribution of SPECT measurements of D2 and 5-HT2A occupancy to the clinical development of the antipsychotic SB-773812. J Nucl Med. 2011;52:526–34.CrossRefGoogle Scholar
  28. 28.
    Min JJ, Gambhir SS. Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects. Gene Ther. 2004;11:115–25.CrossRefGoogle Scholar
  29. 29.
    Camilleri M, Vazquez-Roque M, Iturrino J, Boldingh A, Burton D, McKinzie S, et al. Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;303:G120–8.CrossRefGoogle Scholar
  30. 30.
    Camilleri M, Bharucha AE, Ueno R, Burton D, Thomforde GM, Baxter K, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G942–7.CrossRefGoogle Scholar
  31. 31.
    Delgado-Aros S, Chial HJ, Cremonini F, Ferber I, McKinzie S, Burton DD, et al. Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health. Aliment Pharmacol Ther. 2003;18:507–14.CrossRefGoogle Scholar
  32. 32.
    Townsend DW, Cherry SR. Combining anatomy and function: the path to true image fusion. Eur Radiol. 2001;11:1968–74.CrossRefGoogle Scholar
  33. 33.
    Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000;41:1369–79.Google Scholar
  34. 34.
    Pichler BJ, Judenhofer MS, Pfannenberg C. Multimodal imaging approaches: PET/CT and PET/MRI. Handb Exp Pharmacol. 2008:109–32.Google Scholar
  35. 35.
    Brix G, Lechel U, Glatting G, Ziegler SI, Munzing W, Muller SP, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med. 2005;46:608–13.Google Scholar
  36. 36.
    de Rosales RT. Potential clinical applications of bimodal PET-MRI or SPECT-MRI agents. J Label Compd Radiopharm. 2014;57:298–303.CrossRefGoogle Scholar
  37. 37.
    Sauter AW, Wehrl HF, Kolb A, Judenhofer MS, Pichler BJ. Combined PET/MRI: one step further in multimodality imaging. Trends Mol Med. 2010;16:508–15.CrossRefGoogle Scholar
  38. 38.
    Madsen MT. Recent advances in SPECT imaging. J Nucl Med. 2007;48:661–73.CrossRefGoogle Scholar
  39. 39.
    Fischman AJ, Alpert NM, Rubin RH. Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action. Clin Pharmacokinet. 2002;41:581–602.CrossRefGoogle Scholar
  40. 40.
    Wagner CC, Langer O. Approaches using molecular imaging technology -- use of PET in clinical microdose studies. Adv Drug Deliv Rev. 2011;63:539–46.CrossRefGoogle Scholar
  41. 41.
    Aboagye EO, Price PM, Jones T. In vivo pharmacokinetics and pharmacodynamics in drug development using positron-emission tomography. Drug Discov Today. 2001;6:293–302.CrossRefGoogle Scholar
  42. 42.
    Rudin M, Weissleder R. Molecular imaging in drug discovery and development. Nat Rev Drug Discov. 2003;2:123–31.CrossRefGoogle Scholar
  43. 43.
    Gomes CM, Abrunhosa AJ, Ramos P, Pauwels EK. Molecular imaging with SPECT as a tool for drug development. Adv Drug Deliv Rev. 2011;63:547–54.CrossRefGoogle Scholar
  44. 44.
    Kummar S, Rubinstein L, Kinders R, Parchment RE, Gutierrez ME, Murgo AJ, et al. Phase 0 clinical trials: conceptions and misconceptions. Cancer J. 2008;14:133–7.CrossRefGoogle Scholar
  45. 45.
    Lappin G, Kuhnz W, Jochemsen R, Kneer J, Chaudhary A, Oosterhuis B, et al. Use of microdosing to predict pharmacokinetics at the therapeutic dose: experience with 5 drugs. Clin Pharmacol Ther. 2006;80:203–15.CrossRefGoogle Scholar
  46. 46.
    Saleem A, Harte RJ, Matthews JC, Osman S, Brady F, Luthra SK, et al. Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography. J Clin Oncol. 2001;19:1421–9.CrossRefGoogle Scholar
  47. 47.
    Garner RC, Lappin G. The phase 0 microdosing concept. Br J Clin Pharmacol. 2006;61:367–70.CrossRefGoogle Scholar

Copyright information

© Korean Society of Nuclear Medicine 2019

Authors and Affiliations

  • Hyeomin Son
    • 1
  • Kyungho Jang
    • 2
  • Heechan Lee
    • 1
  • Sang Eun Kim
    • 3
    • 4
  • Keon Wook Kang
    • 5
  • Howard Lee
    • 1
    • 3
    Email author
  1. 1.Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulRepublic of Korea
  2. 2.Center for Clinical Pharmacology, Biomedical Research InstituteChonbuk National University HospitalJeonjuRepublic of Korea
  3. 3.Department of Transdisciplinary Studies, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulRepublic of Korea
  4. 4.Department of Nuclear MedicineSeoul National University College of Medicine and Seoul National University Bundang HospitalSeongnamRepublic of Korea
  5. 5.Department of Nuclear Medicine & Cancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea

Personalised recommendations