nach oben

International Journal of Clinical Oncology

Erschienen in:

10.05.2018 | Original Article

In vivo detection of acute intracellular acidification in glioblastoma multiforme following a single dose of cariporide

verfasst von: Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha

Erschienen in: International Journal of Clinical Oncology | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

Abstract

Glioblastoma is an aggressive brain cancer that is very difficult to treat. Clinically, it is important to be able to distinguish aggressive from non-aggressive brain tumors. Previous studies have shown that some drugs can induce a rapid change in intracellular pH that could help to identify aggressive cancer. The sodium proton exchanger (NHE1) plays a significant role in maintaining pH balance in the tumor microenvironment. Cariporide is a sodium proton exchange inhibitor that is well tolerated by humans in cardiac applications. We hypothesized that cariporide could selectively acidify brain tumors. The purpose of this study was to determine whether amine/amide concentration-independent detection (AACID) chemical exchange saturation transfer (CEST) MRI measurement of tumor pH_i could detect acidification after cariporide injection. Using a 9.4T MRI scanner, CEST spectra were acquired in six mice approximately 14 days after implanting 10⁵ U87 human glioblastoma multiforme cells in the brain, before and after administration of cariporide (dose: 6 mg/kg) by intraperitoneal injection. Three additional mice were studied as controls and received only vehicle injection (DMSO + PBS). Repeated measures t test was used to examine changes in tumor and contralateral tissue regions of interest. Two hours after cariporide injection, there was a significant 0.12 ± 0.03 increase in tumor AACID value corresponding to a 0.48 decrease in pH_i and no change in AACID value in contralateral tissue. A small but significant increase of 0.04 ± 0.017 in tumor AACID value was also observed following vehicle injection. This study demonstrates that acute CEST MRI contrast changes, indicative of intracellular acidification, after administration of cariporide could help localize glioblastoma.

Kanu OO, Mehta A, Di C et al (2009) Glioblastoma multiforme: a review of therapeutic targets. Expert Opin Ther Targets 13(6):701–718. https://doi.org/10.1517/14728220902942348 CrossRefPubMed

Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507. https://doi.org/10.1056/NEJMra0708126 CrossRefPubMed

Sagiyama K, Mashimo T, Togao O et al (2014) In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma. Proc Natl Acad Sci USA 111(12):4542–4547. https://doi.org/10.1073/pnas.1323855111 CrossRefPubMed

Easaw JC, Mason WP, Perry J, Canadian Glioblastoma Recommendations C et al (2011) Canadian recommendations for the treatment of recurrent or progressive glioblastoma multiforme. Curr Oncol 18(3):e126–e136CrossRef

Gerweck LE, Seetharaman K (1996) Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res 56(6):1194–1198PubMed

Stubbs M, Bhujwalla ZM, Tozer GM et al (1992) An assessment of 31P MRS as a method of measuring pH in rat tumours. NMR Biomed 5(6):351–359CrossRef

Ha DH, Choi S, Oh JY et al (2013) Application of 31P MR spectroscopy to the brain tumors. Korean J Radiol 14(3):477–486. https://doi.org/10.3348/kjr.2013.14.3.477 CrossRefPubMedPubMedCentral

Cichocka M, Kozub K, Andrzej U (2015) PH Measurements of the brain using phosphorus magnetic resonance spectroscopy (31PMRS) in healthy men—comparison of two analysis methods. Pol J Radiol. https://doi.org/10.12659/PJR.895178 CrossRefPubMedPubMedCentral

Oberhaensli RD, Galloway GJ, Hilton-Jones D et al (1987) The study of human organs by phosphorus-31 topical magnetic resonance spectroscopy. Br J Radiol 60(712):367–373. https://doi.org/10.1259/0007-1285-60-712-367 CrossRefPubMed

10.

Maintz D, Heindel W, Kugel H et al (2002) Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours. NMR Biomed 15(1):18–27CrossRef

11.

Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4(11):891–899. https://doi.org/10.1038/nrc1478 CrossRefPubMed

12.

Huber V, De Milito A, Harguindey S et al (2010) Proton dynamics in cancer. J Transl Med 8:57. https://doi.org/10.1186/1479-5876-8-57 CrossRefPubMedPubMedCentral

13.

Neri D, Supuran CT (2011) Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 10(10):767–777. https://doi.org/10.1038/nrd3554 CrossRefPubMed

14.

Webb BA, Chimenti M, Jacobson MP, Barber DL (2011) Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 11(9):671–677. https://doi.org/10.1038/nrc3110 CrossRefPubMed

15.

Shrode LD, Tapper H, Grinstein S (1997) Role of intracellular pH in proliferation, transformation, and apoptosis. J Bioenerg Biomembr 29(4):393–399CrossRef

16.

Barar J, Omidi Y (2013) Dysregulated pH in tumor microenvironment checkmates cancer therapy. Bioimpacts 3(4):149–162. https://doi.org/10.5681/bi.2013.036 CrossRefPubMedPubMedCentral

17.

Izumi H, Torigoe T, Ishiguchi H et al (2003) Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev 29(6):541–549. https://doi.org/10.1016/s0305-7372(03)00106-3 CrossRefPubMed

18.

Wood PJ, Sansom JM, Newell K et al (1995) Reduction of tumour intracellular pH and enhancement of melphalan cytotoxicity by the ionophore Nigericin. Int J Cancer 60(2):264–268CrossRef

19.

McVicar N, Li AX, Goncalves DF et al (2014) Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI. J Cereb Blood Flow Metab 34(4):690–698. https://doi.org/10.1038/jcbfm.2014.12 CrossRefPubMedPubMedCentral

20.

McVicar N, Li AX, Meakin SO et al (2015) Imaging chemical exchange saturation transfer (CEST) effects following tumor-selective acidification using lonidamine. NMR Biomed 28(5):566–575. https://doi.org/10.1002/nbm.3287 CrossRefPubMed

21.

Marathe K, McVicar N, Li A et al (2016) Topiramate induces acute intracellular acidification in glioblastoma. J Neurooncol 130(3):465–472. https://doi.org/10.1007/s11060-016-2258-y CrossRefPubMed

22.

Albatany M, Li A, Meakin S et al (2017) Dichloroacetate induced intracellular acidification in glioblastoma: in vivo detection using AACID-CEST MRI at 9.4 T. J Neurooncol. https://doi.org/10.1007/s11060-017-2664-9 CrossRefPubMed

23.

Harguindey S, Arranz JL, Orozco JDP et al (2013) Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs—an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research. J Transl Med 11:282. https://doi.org/10.1186/1479-5876-11-282 CrossRefPubMedPubMedCentral

24.

Scholz W, Albus U, Counillon L et al (1995) Protective effects of HOE642, a selective sodium-hydrogen exchange subtype-1 inhibitor, on cardiac ischemia and reperfusion. Cardiovasc Res 29(2):260–268. https://doi.org/10.1016/S0008-6363(96)88579-8 CrossRefPubMed

25.

McLean LA, Roscoe J, Jorgensen NK et al (2000) Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am J Physiol Cell Physiol 278(4):C676-688CrossRef

26.

Lagana A, Vadnais J, Le PU et al (2000) Regulation of the formation of tumor cell pseudopodia by the Na⁺/H⁺ exchanger NHE1. J Cell Sci 113(20):3649–3662PubMed

27.

Lv C, Yang X, Yu B et al (2012) Blocking the Na⁺/H⁺ exchanger 1 with cariporide (HOE642) reduces the hypoxia-induced invasion of human tongue squamous cell carcinoma. Int J Oral Maxillofac Surg 41(10):1206–1210. https://doi.org/10.1016/j.ijom.2012.03.001 CrossRefPubMed

28.

Hegde M, Roscoe J, Cala P et al (2004) Amiloride kills malignant glioma cells independent of its inhibition of the sodium–hydrogen exchanger. J Pharmacol Exp Ther 310(1):67–74. https://doi.org/10.1124/jpet.103.065029 CrossRefPubMed

29.

Glunde K, Düssmann H, Juretschke HP et al (2002) Na(+)/H(+) exchange subtype 1 inhibition during extracellular acidification and hypoxia in glioma cells. J Neurochem 80(1):36–44CrossRef

30.

Gao W, Chang G, Wang J et al (2011) Inhibition of K562 leukemia angiogenesis and growth by selective Na⁺/H⁺ exchanger inhibitor cariporide through down-regulation of pro-angiogenesis factor VEGF. Leuk Res 35(11):1506–1511. https://doi.org/10.1016/j.leukres.2011.07.001 CrossRefPubMed

31.

Li AX, Suchy M, Li C et al (2011) In vivo detection of MRI-PARACEST agents in mouse brain tumors at 9.4 T. Magn Reson Med 66(1):67–72. https://doi.org/10.1002/mrm.22772 CrossRefPubMed

32.

Kim M, Gillen J, Landman BA et al (2009) Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med 61(6):1441–1450. https://doi.org/10.1002/mrm.21873 CrossRefPubMedPubMedCentral

33.

O’Donnell ME, Chen YJ, Lam TI et al (2013) Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood–brain barrier Na/H exchanger. J Cereb Blood Flow Metab 33(2):225–234. https://doi.org/10.1038/jcbfm.2012.160 CrossRefPubMed

34.

Mokgokong R, Wang S, Taylor CJ et al (2014) Ion transporters in brain endothelial cells that contribute to formation of brain interstitial fluid. Pflug Arch 466(5):887–901. https://doi.org/10.1007/s00424-013-1342-9 CrossRef

35.

Ballabh P, Braun A, Nedergaard M (2004) The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16(1):1–13. https://doi.org/10.1016/j.nbd.2003.12.016 CrossRefPubMed

36.

Gao W, Zhang H, Chang G et al (2014) Decreased intracellular pH induced by cariporide differentially contributes to human umbilical cord-derived mesenchymal stem cells differentiation. Cell Physiol Biochem 33(1):185–194. https://doi.org/10.1159/000356661 CrossRefPubMed

37.

Gao W, Chang GQ, Wang J et al (2011) Inhibition of K562 leukemia angiogenesis and growth by selective Na⁺/H⁺ exchanger inhibitor cariporide through down-regulation of pro-angiogenesis factor VEGF. Leuk Res 35(11):1506–1511. https://doi.org/10.1016/j.leukres.2011.07.001 CrossRefPubMed

38.

Wong P (2001) The potential of two new inhibitors of mechanisms that regulate intracellular pH, cariporide and S3705, to inhibit tumour cell proliferation. Canadian theses = Thèses canadiennes. National Library of Canada, Ottawa

Titel: In vivo detection of acute intracellular acidification in glioblastoma multiforme following a single dose of cariporide
verfasst von: Mohammed Albatany
Alex Li
Susan Meakin
Robert Bartha
Publikationsdatum: 10.05.2018
Verlag: Springer Japan
Erschienen in: International Journal of Clinical Oncology / Ausgabe 5/2018
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-018-1289-0

Neu im Fachgebiet Onkologie

17.04.2024 | Mammakarzinom | Nachrichten

Springer Medizin

In vivo detection of acute intracellular acidification in glioblastoma multiforme following a single dose of cariporide

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2018

Treatment outcomes of patients with spinal metastases derived from hepatocellular carcinoma

Relationships between sunitinib plasma concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma

Feasibility study of postoperative adjuvant chemotherapy with S-1 in patients with biliary tract cancer

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

Intravesical bacillus Calmette–Guerin therapy after second transurethral resection for primary T1 bladder cancer

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism

Neu im Fachgebiet Onkologie

Adjuvante Brustkrebstherapie: Doppelt hält besser

Manche Gestagene können das Risiko für Meningeome erhöhen

Einladung zum PSA-Screening senkt die Krebssterblichkeit

Chemotherapie mit Hindernissen

Update Onkologie