Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

MicroSPECT and MicroPET Imaging of Small Animals for Drug Development

  • Jang, Beom-Su (RI-Biomics Research & Development Team, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
  • Received : 2013.03.04
  • Accepted : 2013.03.18
  • Published : 2013.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

Keywords

References

  1. DiMasi, J.A., Hansen, R.W. and Grabowski, H.G. (2003) The price of innovation: new estimates of drug development costs. J. Health Econ., 22, 151-185. https://doi.org/10.1016/S0167-6296(02)00126-1
  2. Ahn, B.C. (2011) Applications of molecular imaging in drug discovery and development process. Curr. Opin. Biotechnol., 12, 459-468.
  3. Rudin, M. (2009) Noninvasive structural, fuctional, and molecular imaging in drug development.Curr. Opin. Chem. Biol., 13, 360-371. https://doi.org/10.1016/j.cbpa.2009.03.025
  4. Czernin, J., Weber, W.A. and Herschman, H.R. (2006) Molecular imaging in development of cancer therapeutics. Annu. Rev. Med., 57, 99-118. https://doi.org/10.1146/annurev.med.57.080904.190431
  5. Rudin, M. and Weissleder, R. (2003) Molecular imaging in drug discovery and development. Nat. Rev. Drug Discov., 2, 123-131. https://doi.org/10.1038/nrd1007
  6. Ding, H. and Wu, F. (2012) Image guide biodistribution and pharmacokinetic studies of theranostics. Theranostics, 2, 1040-1053. https://doi.org/10.7150/thno.4652
  7. Mankoff, D.A. (2007) A definition of molecular imaging. J. Nucl. Med., 48, 18N, 12N.
  8. Massoud, T.F. and Gambhir, S.S. (2003) Molecular imaging in living subjects: seeing fundermental biological processes in a new light. Genes Dev., 17, 545-580. https://doi.org/10.1101/gad.1047403
  9. Vanderheyden, J.L. (2009) The use of imaging in preclinical drug development. Q. J. Nucl. Med. Mol. Imaging, 53, 374-381.
  10. Massoud, T.F. and Gambhir, S.S. (2007) Integrating noninvasive molecular imaging into molecular medicine: an evolging paradigm. Trends Mol. Med., 13, 183-191. https://doi.org/10.1016/j.molmed.2007.03.003
  11. Cai, W., Rao, J., Gambhir, S.S. and Chen, X. (2006) How molecular imaging is speeding up antiagiogenic drug development. Mol.Cancer Ther., 5, 2624-2633. https://doi.org/10.1158/1535-7163.MCT-06-0395
  12. Lecchi, M., Ottobrini, L., Martelli, C., Del Sole, A. and Lucignani, G. (2007) Instrumentation and probes for molecular and cellular imaging. Q. J. Nucl. Med. Mol. Imaging, 51, 111-126.
  13. Pichler, B.J., Wehrl, H.F. and Judenhofer, M.S. (2008) Latest advances in molecular imaging instrumentation. J. Nucl. Med., 49, 5S-23S. https://doi.org/10.2967/jnumed.108.045880
  14. Koba, W., Jelicks, L.A. and Fine, E.J. (2013) MicroPET/ SPECT/CT imaging of small animal models of disease. Am. J. Pathol., 182, 319-324. https://doi.org/10.1016/j.ajpath.2012.09.025
  15. Koba, W., Kim, K., Lipton, M.L., Jelicks, L., Das, B., Herbst, L. and Fine, E. (2011) Imaging devices for use in small animals. Semin. Nucl. Med., 41, 151-165. https://doi.org/10.1053/j.semnuclmed.2010.12.003
  16. van de Wiele, C., Lahorte, C., Vermeersch, H., Loose, D., Mervillie, K., Steinmetz, N.D., Vanderheyden, J.L., Cuvelier, C.A., Slegers, G. and Dierck, R.A. (2003) Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography. J. Clin. Oncol., 21, 3483-3487. https://doi.org/10.1200/JCO.2003.12.096
  17. Riemann, B., Schafers, K.P., Schober, O. and Schafers, M. (2008) Small animal PET in preclinical studies: oppertunities and chanllenges. Q. J. Nucl. Med. Mol. Imaging, 52, 215-221.
  18. Franc, B.L., Acton, P.D., Mari, C. and Hasegawa, B.H. (2008) Small animal SPECT and SPECT/CT: important tools for preclinical investigation. J. Nucl. Med., 49, 1651-1663. https://doi.org/10.2967/jnumed.108.055442
  19. Toppomg, G.J., Dinelle, K., Kornelsen, R., McCormick, S., Holden, J.E. and Sossi, V. (2010) Positron emission tomography kinetic modeling algorithms for small animal dopaminergic system imaging. Synapses, 64, 200-208. https://doi.org/10.1002/syn.20716
  20. Stacy, M.R., Maxfield, M.W. and Sinusas, A.J. (2012) Targeted molecular imaging of angiogenesis in PET and SPECT: a review. Yale J. Biol. Med., 85, 75-86.
  21. Haubner, R., Wester, H.J., Weber, W.A., Mang, C., Ziegler, S.I., Goodman, S.L., Senekowitsch-Schmidtke, R., Kessler, H. and Schwaiger, M. (2001) Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res., 61, 1781-1785.
  22. Nolting, D.D., Nickels, M.L., Guo, N. and Pham, W. (2012) Molecular imaging probe development: a chemistry perspective. Am. J. Nucl. Med. Mol. Imaging, 2, 273-306.
  23. Lindsay, M.A. (2003) Target discovery. Nat. Rev. Drug Discovery, 2, 831-838. https://doi.org/10.1038/nrd1202
  24. Haberkorn, U. and Altmann, A. (2002) Radionuclide imaging in the post-genomic era. J. Cell. Biochem. Suppl., 39, 1-10.
  25. Begley, D.J. and Brightman, M.W. (2003) Structural and functional aspects of the blood-brain barrier. Prog. Drug Res., 61, 39-78.
  26. Jain, R.K. (1999) Transport of molecules, particles, and cells in solid tumors. Annu. Rev. Biomed. Eng., 1, 241-263. https://doi.org/10.1146/annurev.bioeng.1.1.241
  27. Murakami, Y., Takamatsu, H., Taki, J., Tatsumi, M., Noda, A., Ichise, R., Tait, J.F. and Nishimura, S. (2004) 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur. J. Nucl. Med. Mol. Imaging, 31, 469-474. https://doi.org/10.1007/s00259-003-1378-8
  28. Green, L.A., Yap, C.S., Nguyen, K., Barrio, J.R., Namavari, M., Satyamurthy, N., Phelps, M.E., Sandgren, E.P., Herschman, H.R. and Gambhir, S.S. (2002) Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Mol. Imaging Biol., 4, 71-81. https://doi.org/10.1016/S1095-0397(01)00071-1
  29. Koehne, G., Doubrovin, M., Doubrovina, E., Zanzonico, P., Gallardo, H.F., Ivanova, A, Balatoni, J., Teruya-Feldstein, J., Heller, G., May, C., Ponomarev, V., Ruan, S., Finn, R., Blasberg, R.G., Bornmann, W., Riviere, I., Sadelain, M., O'Reilly, R.J., Larson, S.M. and Tjuvajev, J.G. (2003) Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes. Nat. Biotechnol., 21, 405-413. https://doi.org/10.1038/nbt805
  30. Rogers, B.E., Rosenfeld, M.E., Khazaeli, M.B., Mikheeva, G., Stackhouse, M.A., Liu, T., Curiel, D.T. and Buchsbaum, D.J. (1997) Localization of iodine-125-mIP-Des-Met14-bombesin (7-13)NH2 in ovarian carcinoma induced to express the gastrin releasing peptide receptor by adenoviral vector-mediated gene transfer. J. Nucl. Med., 38, 1221-1229.
  31. Yazaki, P.J., Shively, L., Clark, C., Cheung, C.W., Le, W., Szpikowska, B., Shively, J.E., Raubitschek, A.A. and Wu, A.M. (2001) Mammalian expression and hollow fiber bioreactor production of recombinant anti-CEA diabody and minibody for clinical applications. J. Immunol. Methods, 253, 195-208.
  32. Kao, C.H., Hsieh, J.F., Tsai, S.C., Ho, Y.J. and Lee, J.K. (2000) Quickly predicting chemotherapy response to paclitaxel- based therapy in non-small cell lung cancer by early technetium-99m methoxyisobutylisonitrile chest single-photon- emission computed tomography. Clin. Cancer Res., 6, 820-824.
  33. Wong, D.F., Tauscher, J. and Gründer, G. (2009) The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology, 34, 187-203. https://doi.org/10.1038/npp.2008.166
  34. Paulmurugan, R. and Gambhir, S.S. (2006) An intramolecular folding sensor for imaging estrogen receptor-ligand interactions. Proc. Natl. Acad. Sch. U.S.A., 103, 15883-15888. https://doi.org/10.1073/pnas.0607385103
  35. Massoud, T.F., Paulmurugan, R., De, A, Ray, P. and Gambhir, S.S. (2007) Reportor gene imaging of protein-protein interactions in living subjects. Curr. Opin. Biotechnol., 18, 31-37. https://doi.org/10.1016/j.copbio.2007.01.007

Cited by

  1. Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives vol.11, pp.11, 2014, https://doi.org/10.1021/mp500173s
  2. Animal Models of Bone Metastasis vol.52, pp.5, 2015, https://doi.org/10.1177/0300985815586223
  3. Unbridle biomedical research from the laboratory cage vol.6, pp.2050-084X, 2017, https://doi.org/10.7554/eLife.27438
  4. Rigid motion correction of dual opposed planar projections in single photon imaging vol.62, pp.10, 2017, https://doi.org/10.1088/1361-6560/aa68cd
  5. F-18 fluoride uptake in primary breast cancer pp.1864-6433, 2018, https://doi.org/10.1007/s12149-018-1294-4
  6. Ocular Biodistribution of 89Zr-Bevacizumab in New Zealand Rabbits Determined Using PET/MRI: A Feasibility Study vol.In Press, pp.In Press, 2019, https://doi.org/10.5812/iranjradiol.68697