Molecular Nuclear imaging of Angiogenesis

혈관신생 분자핵의학 영상

  • 이경한 (성균관대학교 의과대학 삼성서울병원 핵의학과)
  • Published : 2004.04.30

Abstract

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.

Keywords

References

  1. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57. https://doi.org/10.1038/35025220
  2. Harris AL. Antiangiogenesis for cancer therapy. Lancet 1997;349:SII13-5.
  3. Weidner N, Semple JP, Welch WR. Folkman J. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8.
  4. Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997;390:404-7. https://doi.org/10.1038/37126
  5. O'Reilly MS, Holmgren L, Chen C, Folkman J. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med 1996;2:689-92. https://doi.org/10.1038/nm0696-689
  6. Casey R, Jaffe M, Li WW, Li VW, Tsakayannis D: Market Study of Angiogenesis-Dependent Diseases: Classification and Sizing of the Potential Market for the Pharmaceutical Industry in the United States and in the European Union. The Angiogenesis Foundation, Cambridge. pp 7-20, 1998.
  7. Weber WA, Haubner R, Vabuliene E, Kuhnast B, Wester HJ, Schwaiger M. Tumor angiogenesis targeting using imaging agents. Q J Nucl Med 2001;45:179-82.
  8. Folkman J, Beckner K. Angiogenesis Imaging. Acad Radiol 2000;7:783-5. https://doi.org/10.1016/S1076-6332(00)80625-X
  9. Miles KA, Charbasabgave JC, Lee FT, Fishman EK, Horton K, Lee TY. Application of CT in the investigation of angiogenesis in oncology. Acad Radiol 2000;7:840-50. https://doi.org/10.1016/S1076-6332(00)80632-7
  10. Brasch RC, Li KC, Husband JE, et al. In vivo monitoring of tumour angiogenesis with MR imaging. Acad Radiol 2000;7:812-23. https://doi.org/10.1016/S1076-6332(00)80630-3
  11. Herschman HR. Molecular imaging: Looking at problems, seeing solutions. Science 2003;302:605-8. https://doi.org/10.1126/science.1090585
  12. Weissleder R and Mahmood U. Molecular imaging. Radiology 2001;219:3160-330.
  13. 이경한. 분자영상: 핵의학적 접근. 대한의협회지 2004;47:119-26.
  14. Costouros NG, Diehn FE, Libutti SK. Molecular imaging of tumor angiogenesis. J Cell Biochem Suppl 2002;39:72-8.
  15. Haubner R, Wester HJ, Reuning U, et al. Radiolabeled $\alpha$v $\beta$3 integrin antagonists: A new calss of tracers for tumor imaging. J Nucl Med 1999;40:1061-71.
  16. Janssen ML, Oyen WJ, Dijkgraaf I, et al. Tumor targeting with radiolabeled $\alpha$v $\beta$3 integrin binding peptides in a nude mouse model. Cancer Res 2002;62:6146-51.
  17. Haubner R, Wester HJ, Weber WA, et al. Noninvasive imaging of $\alpha$v $\beta$3 integrin expression using 18F-labeled RGD containing glycopeptide and positron emission tomography. Cancer Res 2001;61:1781-5.
  18. Lee K-H, Song SH, Paik J-Y, et al. Specific Endothelial binding and tumor uptake of radiolabeled angiostatin. Eur J Nucl Med Mol Imaging 2003;30:1032-37. https://doi.org/10.1007/s00259-002-1094-9
  19. Yang DJ, Kim KD, Schechter NR, et al. Assessment of antiangiogenic effect using $^{99m}Tc$-EC-endostatin. Cancer Biother Radiopharm 2002;17:233-45. https://doi.org/10.1089/108497802753773856