Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Mar;63(3):404–409. doi: 10.1038/bjc.1991.93

The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids.

R J Mairs 1, W Angerson 1, M N Gaze 1, T Murray 1, J W Babich 1, R Reid 1, C McSharry 1
PMCID: PMC1971876  PMID: 2003981

Abstract

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.

Full text

PDF
404

Images in this article

406Figure 1
on p.406
407Figure 2
on p.407
407Figure 3
on p.407
408Figure 4
on p.408

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan P. M., Garson J. A., Harper E. I., Asser U., Coakham H. B., Brownell B., Kemshead J. T. Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues. Int J Cancer. 1983 May 15;31(5):591–598. doi: 10.1002/ijc.2910310510. [DOI] [PubMed] [Google Scholar]
  2. Baker D. L., Reddy U. R., Pleasure D., Thorpe C. L., Evans A. E., Cohen P. S., Ross A. H. Analysis of nerve growth factor receptor expression in human neuroblastoma and neuroepithelioma cell lines. Cancer Res. 1989 Aug 1;49(15):4142–4146. [PubMed] [Google Scholar]
  3. Beierwaltes W. H. Update on basic research and clinical experience with metaiodobenzylguanidine. Med Pediatr Oncol. 1987;15(4):163–169. doi: 10.1002/mpo.2950150405. [DOI] [PubMed] [Google Scholar]
  4. Buck C. R., Martinez H. J., Black I. B., Chao M. V. Developmentally regulated expression of the nerve growth factor receptor gene in the periphery and brain. Proc Natl Acad Sci U S A. 1987 May;84(9):3060–3063. doi: 10.1073/pnas.84.9.3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carachi R., Raza T., Robertson D., Wheldon T. W., Wilson L., Livingstone A., van Heyningen V., Spowart G., Middleton P., Gosden J. R. Biological properties of a tumour cell line (NB1-G) derived from human neuroblastoma. Br J Cancer. 1987 Apr;55(4):407–411. doi: 10.1038/bjc.1987.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamilton T. C., Young R. C., McKoy W. M., Grotzinger K. R., Green J. A., Chu E. W., Whang-Peng J., Rogan A. M., Green W. R., Ozols R. F. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983 Nov;43(11):5379–5389. [PubMed] [Google Scholar]
  8. Humm J. L. Dosimetric aspects of radiolabeled antibodies for tumor therapy. J Nucl Med. 1986 Sep;27(9):1490–1497. [PubMed] [Google Scholar]
  9. Jaques S., Jr, Tobes M. C., Sisson J. C., Baker J. A., Wieland D. M. Comparison of the sodium dependency of uptake of meta-lodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol. 1984 Nov;26(3):539–546. [PubMed] [Google Scholar]
  10. Jaques S., Jr, Tobes M. C., Sisson J. C. Sodium dependency of uptake of norepinephrine and m-iodobenzylguanidine into cultured human pheochromocytoma cells: evidence for uptake-one. Cancer Res. 1987 Aug 1;47(15):3920–3928. [PubMed] [Google Scholar]
  11. Kemshead J. T., Lashford L. S., Jones D. H., Coakham H. B. Diagnosis and therapy of neuroectodermally associated tumours using targeted radiation. Dev Neurosci. 1987;9(2):69–83. doi: 10.1159/000111611. [DOI] [PubMed] [Google Scholar]
  12. Lashford L. S., Moyes J., Ott R., Fielding S., Babich J., Mellors S., Gordon I., Evans K., Kemshead J. T. The biodistribution and pharmacokinetics of meta-iodobenzylguanidine in childhood neuroblastoma. Eur J Nucl Med. 1988;13(11):574–577. doi: 10.1007/BF02574771. [DOI] [PubMed] [Google Scholar]
  13. Link E. M., Brown I., Carpenter R. N., Mitchell J. S. Uptake and therapeutic effectiveness of 125I- and 211At-methylene blue for pigmented melanoma in an animal model system. Cancer Res. 1989 Aug 1;49(15):4332–4337. [PubMed] [Google Scholar]
  14. Mobley W. C., Schenker A., Shooter E. M. Characterization and isolation of proteolytically modified nerve growth factor. Biochemistry. 1976 Dec 14;15(25):5543–5552. doi: 10.1021/bi00670a019. [DOI] [PubMed] [Google Scholar]
  15. Moyes J. S., Babich J. W., Carter R., Meller S. T., Agrawal M., McElwain T. J. Quantitative study of radioiodinated metaiodobenzylguanidine uptake in children with neuroblastoma: correlation with tumor histopathology. J Nucl Med. 1989 Apr;30(4):474–480. [PubMed] [Google Scholar]
  16. Paffenholz V., Ebener U., Kornhuber B. Uptake and release of iodine-labelled m-iodobenzylguanidine in a neuroblastoma cell culture system and its importance in neuroblastoma therapy. J Cancer Res Clin Oncol. 1989;115(3):269–275. doi: 10.1007/BF00391701. [DOI] [PubMed] [Google Scholar]
  17. Smets L. A., Loesberg C., Janssen M., Metwally E. A., Huiskamp R. Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells. Cancer Res. 1989 Jun 1;49(11):2941–2944. [PubMed] [Google Scholar]
  18. Sonnenfeld K. H., Ishii D. N. Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines. J Neurosci Res. 1982;8(2-3):375–391. doi: 10.1002/jnr.490080226. [DOI] [PubMed] [Google Scholar]
  19. Stach R. W., Perez-Polo J. R. Binding of nerve growth factor to its receptor. J Neurosci Res. 1987;17(1):1–10. doi: 10.1002/jnr.490170102. [DOI] [PubMed] [Google Scholar]
  20. Walker K. A., Murray T., Hilditch T. E., Wheldon T. E., Gregor A., Hann I. M. A tumour spheroid model for antibody-targeted therapy of micrometastases. Br J Cancer. 1988 Jul;58(1):13–16. doi: 10.1038/bjc.1988.152. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES