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


CONCLUSIONS
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.
Buchhorn
H Matthias
HM
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
Seidl
Christof
C
Beck
Roswitha
R
Saur
Dieter
D
Apostolidis
Christos
C
Morgenstern
Alfred
A
Schwaiger
Markus
M
Senekowitsch-Schmidtke
Reingard
R
D000818:Animals; D001729:Bismuth / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D008156:Luciferases / Q000378:metabolism; D049449:Luminescence; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000628:therapy; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D014162:Transfection
D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008156:Luciferases; D001729:Bismuth