Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Feb;71(2):383–387. doi: 10.1038/bjc.1995.78

Accumulation of 99mTc-low-density lipoprotein in human malignant glioma.

J Leppälä 1, M Kallio 1, T Nikula 1, P Nikkinen 1, K Liewendahl 1, J Jääskeläinen 1, S Savolainen 1, H Gylling 1, J Hiltunen 1, J Callaway 1, et al.
PMCID: PMC2033577  PMID: 7841057

Abstract

Low-density lipoprotein (LDL) uptake in gliomas was studied to find out if LDL has potential as a drug carrier of boron, especially for boron neutron capture therapy. Single photon emission tomography (SPET) was performed 2 h and 20 h after intravenous injection of autologous 99mTc-labelled LDL in four patients with untreated and five patients with recurrent glioma. 99mTc-LDL uptake was compared with the uptake of 99mTc-labelled human serum albumin (HSA), an established blood pool marker. The intra- and peritumoral distributions of radioactivity in the SPET images were not identical for radiolabelled LDL and HSA. The mean LDL tumour to brain ratio, determined from transversal SPET slices at 20 h post injection, was 1.5 in untreated and 2.2 in recurrent gliomas; the corresponding ratios for HSA were 1.6 and 3.4. The brain to blood ratio remained constant at 2 h and 20 h in both types of tumours. These data are not consistent with highly selective, homogeneous uptake of LDL in gliomas. However, the different tumoral distribution and rate of uptake of 99mTc-LDL, as compared with 99mTc-HSA, indicate that the uptake of LDL is different from that of HSA and that further studies on the mechanism of LDL uptake in glioma are warranted.

Full text

PDF
383

Images in this article

384Figure 1
on p.384
385Figure 2
on p.385
385Figure 3
on p.385
386Figure 4
on p.386

Selected References

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

  1. Barth R. F., Soloway A. H., Fairchild R. G., Brugger R. M. Boron neutron capture therapy for cancer. Realities and prospects. Cancer. 1992 Dec 15;70(12):2995–3007. doi: 10.1002/1097-0142(19921215)70:12<2995::aid-cncr2820701243>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
  3. Dewit L., Moss R., Gabel D. New developments in neutron capture therapy. Eur J Cancer. 1990;26(8):912–914. doi: 10.1016/0277-5379(90)90199-4. [DOI] [PubMed] [Google Scholar]
  4. Filipowska D., Filipowski T., Morelowska B., Kazanowska W., Laudanski T., Lapinjoki S., Akerlund M., Breeze A. Treatment of cancer patients with a low-density-lipoprotein delivery vehicle containing a cytotoxic drug. Cancer Chemother Pharmacol. 1992;29(5):396–400. doi: 10.1007/BF00686010. [DOI] [PubMed] [Google Scholar]
  5. Fogelholm R., Uutela T., Murros K. Epidemiology of central nervous system neoplasms. A regional survey in Central Finland. Acta Neurol Scand. 1984 Mar;69(3):129–136. doi: 10.1111/j.1600-0404.1984.tb07791.x. [DOI] [PubMed] [Google Scholar]
  6. Gal D., Ohashi M., MacDonald P. C., Buchsbaum H. J., Simpson E. R. Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms. Am J Obstet Gynecol. 1981 Apr 15;139(8):877–885. doi: 10.1016/0002-9378(81)90952-2. [DOI] [PubMed] [Google Scholar]
  7. Haritz D., Gabel D., Huiskamp R. Clinical phase-I study of Na2B12H11SH (BSH) in patients with malignant glioma as precondition for boron neutron capture therapy (BNCT). Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1175–1181. doi: 10.1016/0360-3016(94)90492-8. [DOI] [PubMed] [Google Scholar]
  8. Kahl S. B., Callaway J. C. New tumor localizers: advances in the use of low density lipoproteins (LDL). Strahlenther Onkol. 1989 Feb-Mar;165(2-3):137–139. [PubMed] [Google Scholar]
  9. Kallio M., Sankila R., Jäskeläinen J., Karjalainen S., Hakulinen T. A population-based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984. Cancer. 1991 Sep 15;68(6):1394–1400. doi: 10.1002/1097-0142(19910915)68:6<1394::aid-cncr2820680636>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  10. Kesaniemi Y. A., Witztum J. L., Steinbrecher U. P. Receptor-mediated catabolism of low density lipoprotein in man. Quantitation using glucosylated low density lipoprotein. J Clin Invest. 1983 Apr;71(4):950–959. doi: 10.1172/JCI110849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Larsson S. A. Gamma camera emission tomography. Development and properties of a multi-sectional emission computed tomography system. Acta Radiol Suppl. 1980;363:1–75. [PubMed] [Google Scholar]
  12. Laster B. H., Kahl S. B., Popenoe E. A., Pate D. W., Fairchild R. G. Biological efficacy of boronated low-density lipoprotein for boron neutron capture therapy as measured in cell culture. Cancer Res. 1991 Sep 1;51(17):4588–4593. [PubMed] [Google Scholar]
  13. Lees R. S., Garabedian H. D., Lees A. M., Schumacher D. J., Miller A., Isaacsohn J. L., Derksen A., Strauss H. W. Technetium-99m low density lipoproteins: preparation and biodistribution. J Nucl Med. 1985 Sep;26(9):1056–1062. [PubMed] [Google Scholar]
  14. Leitha T., Staudenherz A., Gmeiner B., Hermann M., Hüttinger M., Dudczak R. Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. II. In vivo validation, LDL receptor-dependent and unspecific hepatic uptake and scintigraphic results. Eur J Nucl Med. 1993 Aug;20(8):674–679. doi: 10.1007/BF00181757. [DOI] [PubMed] [Google Scholar]
  15. McComb R. D., Bigner D. D. The biology of malignant gliomas--a comprehensive survey. Clin Neuropathol. 1984 May-Jun;3(3):93–106. [PubMed] [Google Scholar]
  16. Murakami M., Ushio Y., Mihara Y., Kuratsu J., Horiuchi S., Morino Y. Cholesterol uptake by human glioma cells via receptor-mediated endocytosis of low-density lipoprotein. J Neurosurg. 1990 Nov;73(5):760–767. doi: 10.3171/jns.1990.73.5.0760. [DOI] [PubMed] [Google Scholar]
  17. Nikkinen P., Liewendahl K., Savolainen S., Launes J. Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera. Eur J Nucl Med. 1993 Aug;20(8):680–683. doi: 10.1007/BF00181758. [DOI] [PubMed] [Google Scholar]
  18. Rudling M. J., Angelin B., Peterson C. O., Collins V. P. Low density lipoprotein receptor activity in human intracranial tumors and its relation to the cholesterol requirement. Cancer Res. 1990 Feb 1;50(3):483–487. [PubMed] [Google Scholar]
  19. Thakur M. L., DeFulvio J. D. Technetium-99m-labeled monoclonal antibodies for immunoscintigraphy. Simplified preparation and evaluation. J Immunol Methods. 1991 Mar 21;137(2):217–224. doi: 10.1016/0022-1759(91)90027-d. [DOI] [PubMed] [Google Scholar]
  20. Vallabhajosula S., Paidi M., Badimon J. J., Le N. A., Goldsmith S. J., Fuster V., Ginsberg H. N. Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations. J Nucl Med. 1988 Jul;29(7):1237–1245. [PubMed] [Google Scholar]
  21. Virgolini I., Rauscha F., Lupattelli G., Angelberger P., Ventura A., O'Grady J., Sinzinger H. Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage. Eur J Nucl Med. 1991;18(12):948–951. doi: 10.1007/BF00180413. [DOI] [PubMed] [Google Scholar]
  22. Vitols S., Angelin B., Ericsson S., Gahrton G., Juliusson G., Masquelier M., Paul C., Peterson C., Rudling M., Söderberg-Reid K. Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2598–2602. doi: 10.1073/pnas.87.7.2598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Vitols S., Peterson C., Larsson O., Holm P., Aberg B. Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo. Cancer Res. 1992 Nov 15;52(22):6244–6247. [PubMed] [Google Scholar]
  24. Vitols S. Uptake of low-density lipoprotein by malignant cells--possible therapeutic applications. Cancer Cells. 1991 Dec;3(12):488–495. [PubMed] [Google Scholar]

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

RESOURCES