Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Apr;67(4):701–705. doi: 10.1038/bjc.1993.129

Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

R Kubota 1, S Yamada 1, K Ishiwata 1, M Tada 1, T Ido 1, K Kubota 1
PMCID: PMC1968364  PMID: 8471428

Abstract

The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content.

Full text

PDF
705

Images in this article

702Figure 1
on p.702

Selected References

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

  1. Bagby S. P., O'Reilly M. M., Kirk E. A., Mitchell L. H., Stenberg P. E., Makler M. T., Bakke A. C. EGF is incomplete mitogen in porcine aortic smooth muscle cells: DNA synthesis without cell division. Am J Physiol. 1992 Mar;262(3 Pt 1):C578–C588. doi: 10.1152/ajpcell.1992.262.3.C578. [DOI] [PubMed] [Google Scholar]
  2. Barth R. F., Soloway A. H., Fairchild R. G. Boron neutron capture therapy of cancer. Cancer Res. 1990 Feb 15;50(4):1061–1070. [PubMed] [Google Scholar]
  3. Bennett D. C. Differentiation in mouse melanoma cells: initial reversibility and an on-off stochastic model. Cell. 1983 Sep;34(2):445–453. doi: 10.1016/0092-8674(83)90378-1. [DOI] [PubMed] [Google Scholar]
  4. Coderre J. A., Glass J. D., Fairchild R. G., Roy U., Cohen S., Fand I. Selective targeting of boronophenylalanine to melanoma in BALB/c mice for neutron capture therapy. Cancer Res. 1987 Dec 1;47(23):6377–6383. [PubMed] [Google Scholar]
  5. Coderre J. A., Kalef-Ezra J. A., Fairchild R. G., Micca P. L., Reinstein L. E., Glass J. D. Boron neutron capture therapy of a murine melanoma. Cancer Res. 1988 Nov 15;48(22):6313–6316. [PubMed] [Google Scholar]
  6. Cory J. G., Whitford T. W., Jr Ribonucleotide reductase and DNA synthesis in Ehrlich ascites tumor cells. Cancer Res. 1972 Jun;32(6):1301–1306. [PubMed] [Google Scholar]
  7. Harada J. J., Morris D. R. Cell cycle parameters of Chinese hamster ovary cells during exponential, polyamine-limited growth. Mol Cell Biol. 1981 Jul;1(7):594–599. doi: 10.1128/mcb.1.7.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hessels J., Kingma A. W., Muskiet F. A., Sarhan S., Seiler N. Growth inhibition of two solid tumors in mice, caused by polyamine depletion, is not attended by alterations in cell-cycle phase distribution. Int J Cancer. 1991 Jul 9;48(5):697–703. doi: 10.1002/ijc.2910480512. [DOI] [PubMed] [Google Scholar]
  9. Ichihashi M., Nakanishi T., Mishima Y. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation. J Invest Dermatol. 1982 Mar;78(3):215–218. doi: 10.1111/1523-1747.ep12506489. [DOI] [PubMed] [Google Scholar]
  10. Ishiwata K., Ido T., Honda C., Kawamura M., Ichihashi M., Mishima Y. 4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET. Int J Rad Appl Instrum B. 1992 Apr;19(3):311–318. doi: 10.1016/0883-2897(92)90116-g. [DOI] [PubMed] [Google Scholar]
  11. Ishiwata K., Ido T., Kawamura M., Kubota K., Ichihashi M., Mishima Y. 4-Borono-2-[18F]fluoro-D,L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography. Int J Rad Appl Instrum B. 1991;18(7):745–751. doi: 10.1016/0883-2897(91)90013-b. [DOI] [PubMed] [Google Scholar]
  12. Ishiwata K., Kubota K., Kubota R., Iwata R., Takahashi T., Ido T. Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanomas. J Nucl Med. 1991 Jan;32(1):95–101. [PubMed] [Google Scholar]
  13. Ishiwata K., Shiono M., Kubota K., Yoshino K., Hatazawa J., Ido T., Honda C., Ichihashi M., Mishima Y. A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine. Melanoma Res. 1992 Sep;2(3):171–179. doi: 10.1097/00008390-199209000-00005. [DOI] [PubMed] [Google Scholar]
  14. Kubota K., Kubota R., Matsuzawa T. Dose-responsive growth inhibition by glucocorticoid and its receptors in mouse teratocarcinoma OTT6050 in vivo. Cancer Res. 1983 Feb;43(2):787–793. [PubMed] [Google Scholar]
  15. Kubota R., Yamada S., Ishiwata K., Kubota K., Ido T. Active melanogenesis in non-S phase melanocytes in B16 melanomas in vivo investigated by double-tracer microautoradiography with 18F-fluorodopa and 3H-thymidine. Br J Cancer. 1992 Oct;66(4):614–618. doi: 10.1038/bjc.1992.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kubota R., Yamada S., Kubota K., Ishiwata K., Tamahashi N., Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med. 1992 Nov;33(11):1972–1980. [PubMed] [Google Scholar]
  17. Mishima Y., Honda C., Ichihashi M., Obara H., Hiratsuka J., Fukuda H., Karashima H., Kobayashi T., Kanda K., Yoshino K. Treatment of malignant melanoma by single thermal neutron capture therapy with melanoma-seeking 10B-compound. Lancet. 1989 Aug 12;2(8659):388–389. doi: 10.1016/s0140-6736(89)90567-9. [DOI] [PubMed] [Google Scholar]
  18. Mishima Y., Ichihashi M., Tsuji M., Hatta S., Ueda M., Honda C., Suzuki T. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound. J Invest Dermatol. 1989 May;92(5 Suppl):321S–325S. doi: 10.1111/1523-1747.ep13076750. [DOI] [PubMed] [Google Scholar]
  19. Santavenere E., Cataldi A., Rana R., Vitale M., Lisio R., Di Domenicantonio L., Zamai L., Trubiani O., Miscia S. Nuclear metabolic changes induced by tumor necrosis factor in Daudi lymphoma cells; a multiparametric analysis. Cell Biol Int Rep. 1991 Dec;15(12):1235–1242. doi: 10.1016/0309-1651(91)90095-z. [DOI] [PubMed] [Google Scholar]
  20. Skog S., He Q., Tribukait B. Lack of correlation between thymidine kinase activity and changes of DNA synthesis with tumour age: an in vivo study in Ehrlich ascites tumour. Cell Tissue Kinet. 1990 Nov;23(6):603–617. doi: 10.1111/j.1365-2184.1990.tb01349.x. [DOI] [PubMed] [Google Scholar]
  21. Tsuji M., Ichihashi M., Mishima Y. [Selective affinity of 10B1-paraboronophenylalanine-HCl to malignant melanoma: thermal neutron capture therapy]. Nihon Hifuka Gakkai Zasshi. 1983 Jun;93(7):773–778. [PubMed] [Google Scholar]
  22. Yamada S., Kubota R., Kubota K., Ishiwata K., Ido T. Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography. Neurosci Lett. 1990 Dec 11;120(2):191–193. doi: 10.1016/0304-3940(90)90035-8. [DOI] [PubMed] [Google Scholar]

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

RESOURCES