Non-invasive visualisation of the development of peritoneal carcinomatosis and tumour regression after 213Bi-radioimmunotherapy using bioluminescence imaging

Eur J Nucl Med Mol Imaging. 2007 Jun;34(6):841-9. doi: 10.1007/s00259-006-0311-3. Epub 2007 Jan 6.

Abstract

Purpose: Non-invasive imaging of tumour development remains a challenge, especially for tumours in the intraperitoneal cavity. Therefore, the aim of this study was the visualisation of both the development of peritoneal carcinomatosis and tumour regression after radioimmunotherapy with tumour-specific 213Bi-Immunoconjugates, via in vivo bioluminescence imaging of firefly luciferase-transfected cells.

Methods: Human diffuse-type gastric cancer cells expressing mutant d9-E-cadherin were stably transfected with firefly luciferase (HSC45-M2-luc). For bioluminescence imaging, nude mice were inoculated intraperitoneally with 1x10(7) HSC45-M2-luc cells. On days 4 and 8 after tumour cell inoculation, imaging was performed following D-luciferin injection using a cooled CCD camera with an image intensifier unit. For therapy, mice were injected with 2.7 MBq 213Bi-d9MAb targeting d9-E-cadherin on day 8 after tumour cell inoculation. Bioluminescence images were taken every 4 days to monitor tumour development.

Results: After i.p. inoculation of HSC45-M2-luc cells into nude mice, development as well as localisation of peritoneal carcinomatosis could be visualised using bioluminescence imaging. Following 213Bi-d9MAb therapy on day 8 after intraperitoneal inoculation of HSC45-M2-luc cells, small tumour nodules were totally eliminated and larger nodules showed a clear reduction in size on day 12 after tumour cell inoculation. Subsequently a recurrence of tumour mass was observed, starting from the remaining tumour spots. By measuring the mean grey level intensity, tumour development over time could be demonstrated.

Conclusion: Non-invasive bioluminescence imaging permits visualisation of the development of peritoneal carcinomatosis, localisation of tumour in the intraperitoneal cavity and evaluation of therapeutic success after 213Bi-d9MAb treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bismuth / therapeutic use*
  • Cell Line, Tumor
  • Diagnostic Imaging / methods
  • Luciferases / metabolism
  • Luminescence
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Peritoneal Neoplasms / diagnosis*
  • Peritoneal Neoplasms / therapy
  • Radioimmunotherapy / methods*
  • Radioisotopes / therapeutic use*
  • Radionuclide Imaging
  • Radiopharmaceuticals / therapeutic use*
  • Stomach Neoplasms / diagnostic imaging
  • Stomach Neoplasms / metabolism
  • Transfection

Substances

  • Radioisotopes
  • Radiopharmaceuticals
  • Luciferases
  • Bismuth