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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2007 | Molecular Imaging

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

Authors: H. Matthias Buchhorn, Christof Seidl, Roswitha Beck, Dieter Saur, Christos Apostolidis, Alfred Morgenstern, Markus Schwaiger, Reingard Senekowitsch-Schmidtke

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2007

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 1 × 10⁷ 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.

Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 2000;88:358–63.PubMedCrossRef

Rosenberg R, Nekarda H, Bauer P, Schenck U, Hoefler H, Siewert JR. Free peritoneal tumor cells are an independent prognostic factor in curatively resected stage IB gastric carcinoma. Br J Surg 2006;93:325–31.PubMedCrossRef

Courturier O, Supiot S, Degraef-Mougin M, Faivre-Chauvet A, Carlier T, Chatal JF, et al. Cancer radioimmunotherapy with alpha-emitting nuclides. Eur J Nucl Med Mol Imaging 2005;32:601–14.CrossRef

Borchardt PE, Yuan RR, Miederer M, McDevitt MR, Scheinberg DA. Targeted actinium-225 in vivo generators for therapy of ovarian cancer. Cancer Res 2003;63:5084–90.PubMed

Milenic D, Garmestani K, Dadachova E, Chappell L, Albert P, Hill D, et al. Radioimmunotherapy of human colon carcinoma xenografts using a ²¹³Bi-labeled domain-deleted humanized monoclonal antibody. Cancer Biother Radiopharm 2004;19:135–47.PubMedCrossRef

Qu CF, Song EY, Li Y, Rizvi SM, Raja C, Smith R, et al. Pre-clinical study of ²¹³Bi labelled PAI2 for the control of micrometastatic pancreatic cancer. Clin Exp Metastasis 2005;22:575–86.PubMedCrossRef

Rizvi SMA, Li Y, Song EYJ, Qu CF, Raja C, Morgenstern A, et al. Preclinical studies of bismuth-213 labeled plasminogen activator inhibitor type 2 (PAI2) in a prostate cancer nude mouse xenograft model. Cancer Biol Ther 2006;5:386–93.CrossRef

Jurcic JG, Larson SM, Sgouros G, McDevitt MR, Finn RD, Divgi CR, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood 2002;100:1233–9.PubMed

Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging 2004;48:289–96.PubMed

10.

Nikula TK, McDevitt MR, Finn RD, Wu C, Kozak RW, Garmestani K, et al. Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: pharmacokinetics, bioactivity, toxicity and chemistry. J Nucl Med 1999;40:166–76.PubMed

11.

McDevitt MR, Barendswaard E, Ma D, Lai L, Curcio MJ, Sgouros G, et al. An α-particle emitting antibody ([²¹³Bi]J591) for radioimmuntherapy of prostate cancer. Cancer Res 2000;60:6095–100.PubMed

12.

Senekowitsch-Schmidtke R, Schumacher C, Becker K-F, Nikula TK, Seidl C, Becker I, et al. Highly specific tumor binding of a ²¹³Bi-labeled monoclonal antibody against mutant E-cadherin suggests its usefulness for locoregional α-radioimmunotherapy of diffuse-type gastric cancer. Cancer Res 2001;61:2804–8.PubMed

13.

Miederer M, Seidl C, Beyer GJ, Charlton DE, Vranjes-Duric S, Comor JJ, et al. Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein. Radiat Res 2003;159:612–20.PubMedCrossRef

14.

Huber R, Seidl C, Schmid E, Seidenschwang S, Becker K-F, Schumacher C, et al. Locoregional α-radioimmunotherapy of intraperitoneal tumor cell dissemination using a tumor specific monoclonal antibody. Clin Cancer Res 2003;9:3922s–8s.PubMed

15.

Bloechl S, Beck R, Seidl C, Morgenstern A, Schwaiger M, Senekowitsch-Schmidtke R. Fractionated locoregional low-dose radioimmunotherapy improves survival in a mouse model of diffuse-type gastric cancer using a ²¹³Bi-conjugated monoclonal antibody. Clin Cancer Res 2005;11:7070s–4s.PubMedCrossRef

16.

Seidl C, Schröck H, Seidenschwang S, Beck R, Schmid E, Abend M, et al. Cell death triggered by alpha-emitting ²¹³Bi-immunoconjugates in HSC gastric cancer cells is different from apoptotic cell death. Eur J Nucl Med Mol Imaging 2005;32:274–85.PubMedCrossRef

17.

Zeamari S, Rumping G, Floot B, Lyons S, Stewart FA. In vivo bioluminescence imaging of locally disseminated colon carcinoma in rats. Br J Cancer 2004;90:1259–64.PubMedCrossRef

18.

Vooijs M, Jonkers J, Lyons S, Berns A. Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res 2002;62:1862–7.PubMed

19.

Edinger M, Cao YA, Verneris MR, Bachmann MH, Contag CH, Negrin RS. Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood 2003;101:640–8.PubMedCrossRef

20.

Rehemtulla A, Stegman LD, Cardozo SJ, Gupta S, Hall DE, Contag CH, et al. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2000;2:491–5.PubMedCrossRef

21.

Edinger M, Sweeney TJ, Tucker AA, Olomu AB, Negrin RS, Contag CH. Noninvasive assessment of tumor cell proliferation in animal models. Neoplasia 1999;1:303–10.PubMedCrossRef

22.

Sweeney TJ, Mailänder V, Tucker AA, Olomu AB, Zhang W, Cao YA, et al. Visualizing the kinetics of tumor-cell clearance in living animals. Proc Natl Acad Sci USA 1999;96:12044–9.PubMedCrossRef

23.

Saur D, Seidler B, Schneider G, Algul H, Beck R, Senekowitsch-Schmidtke R, et al. CXCR4 expression increases liver and lung metastasis in a mouse model of pancreatic cancer. Gastroenterology 2005;129:1344–7.CrossRef

24.

Yanagihara K, Ito A, Toge T, Numoto M. Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res 1993;53:5815–21.PubMed

25.

Fukodome Y, Yanagihara K, Takeichi M, Ito F, Shibamoto S. Characterization of a mutant E-cadherin protein encoded by a mutant gene frequently seen in diffuse-type human gastric carcinoma. Int J Cancer 2000;88:579–83.CrossRef

26.

Becker K-F, Kremmer E, Eulitz M, Becker I, Handschuh G, Schumacher C, et al. Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody. Am J Pathol 1999;155:1803–9.PubMed

27.

Mirzadeh S, Brechbiel MW, Atcher RW, Gansow OA. Radiometal labeling of immunoproteins: covalent linkage of 2-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid ligands to immunoglobulin. Bioconjug Chem 1990;1:59–65.PubMedCrossRef

28.

Apostolidis C, Carlos-Marquez R, Janssens W, Molinet R, Nikula T, Ouadi A. Cancer treatment using Bi-213 and Ac-225 in radioimminotherapy. Nucl News 2001;44:29–33.

29.

Apostolidis C, Molinet R, Rasmussen G, Morgenstern A. Production of Ac-225 from Th-229 for targeted alpha-therapy. Anal Chem. 2005;77:6288–91.PubMedCrossRef

30.

Paroo Z, Bollinger RA, Braasch DA, Richer E, Corey DR, Antich PP, et al. Validating bioluminescence imaging as a high-throughput, quantitative modality for assessing tumor burden. Mol Imaging 2004;3:117–24.PubMedCrossRef

31.

Hastings JW. Chemistries and colors of bioluminescent reactions: a review. Gene 1996;173:5–11.PubMedCrossRef

32.

Sato A, Klaumberg B, Tolwani R. In vivo bioluminescence imaging. Comp Med 2004;54:631–4.PubMed

33.

Welsh DK, Kay SA. Bioluminescence imaging in living organisms. Curr Opin Biotechnol 2005;16:73–8.PubMedCrossRef

34.

Virostko J, Chen Z, Fowler M, Poffenberger G, Powers AC, Jansen ED. Factors influencing quantification of in vivo bioluminescence imaging: application to assessment of pancreatic islet transplants. Mol Imaging 2004;3:333–42.PubMedCrossRef

35.

Doubrovin M, Serganova I, Mayer-Kuckuk P, Ponomarev V, Blasberg RG. Multimodality in vivo molecular-genetic imaging. Bioconjug Chem 2004;15:1376–88.PubMedCrossRef

Title: Non-invasive visualisation of the development of peritoneal carcinomatosis and tumour regression after 213Bi-radioimmunotherapy using bioluminescence imaging
Authors: H. Matthias Buchhorn
Christof Seidl
Roswitha Beck
Dieter Saur
Christos Apostolidis
Alfred Morgenstern
Markus Schwaiger
Reingard Senekowitsch-Schmidtke
Publication date: 01-06-2007
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0311-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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