Skip to main content
SpringerLink
Log in

In vitro incorporation studies of 99mTc–alendronate sodium at different bone cell lines

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Bisphosphonates can be labeled with Technetium-99m (99mTc) and are used for bone imaging because of their good localization in the skeleton and rapid clearance from soft tissues. Over the last decades bone scintigraphy has been used extensively in the evaluation of oncological patients to provide information about the sites of bone lesions, their prognosis and the effectiveness of therapy by showing the sequential changes in tracer uptake. Since the lesion visualization and lesion/bone ratio are important utilities for a bone scanning radiopharmaceutic; in this study incorporation of 99mTc labeled alendronate sodium (99mTc–ALD) was evaluated in U2OS (human bone osteosarcoma) and NCI-H209 (human bone carcinoma) cell lines. ALD was directly labeled by 99mTc, radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. For cell incorporation study, NCI-H209 and U2OS cell lines were used with standard cell culture methods. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its transepithelial electrical resistance (TEER) with an epithelial voltammeter. Results confirmed that ALD was successfully radiolabeled with 99mTc. 99mTc–ALD incorporated with NCI-H209 and U2OS cells. The uptake percentages of 99mTc–ALD in NCI-H209 and U2OS cell lines were found significantly different. Since 99mTc–ALD highly uptake in cancer cell line, the results demonstrated that radiolabeled ALD may be a promising agent for bone cancer diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Nakai T, Okuyama C, Kubota T, Yamada K, Ushijima Y, Taniike K, Suzuki T, Nishimura T (2005) Pitfalls of FDG-PET for the diagnosis of osteoblastic bone metastases in patients with breast cancer. Eur J Nucl Med Mol Imag 32(11):1253–1258

    Article  Google Scholar 

  2. Bury T, Barreto A, Daenen F, Barthelemy N, Ghaye B, Rigo P et al (1998) Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer. Eur J Nucl Med 25:1244–1247

    Article  CAS  Google Scholar 

  3. Schirrmeister H, Guhlmann A, Elsner K, Kotzerke J, Glatting G, Rentschler M, Neumaier B, Trager H, Nassle K, Reske SN (1999) Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med 40:1623–1629

    CAS  Google Scholar 

  4. Matthew RA, David BB (2007) Mineralization, microdamage, and matrix: how bisphosphonates influence material properties of bone. BoneKEy-Osteovision 4(2):49–60

    Article  Google Scholar 

  5. Nancollasa GH, Tanga R, Phippsb RJ, Hennemana Z, Guldea S, Wua W, Mangooda A, Russellc RGG, Ebetinob FH (2006) Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38(5):617–627

    Article  Google Scholar 

  6. Bagi CM (2005) Targeting of therapeutic agents to bone to treat metastatic cancer. Adv Drug Deliv Rev 57:995–1010

    Article  CAS  Google Scholar 

  7. Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176

    Article  CAS  Google Scholar 

  8. Bartl R, Frisch B, Tresckow E, Bartl C (2007) Bisphosphonates. In: Schröder GM (ed) Bisphosphonates in medical practice: actions–side effects–indications–strategies. Springer, Berlin, pp 33–70

    Google Scholar 

  9. Bombardieri E, Aktolun C, Baum A, Bishof-Delaloye JB, François Chatal J, Maffioli L, Moncayo R, Mortelmans LRP, Reske SN (2003) Bone scintigraphy: procedure guidelines for tumor imaging. Eur J Nucl Med Mol Imaging 30(12):BP99–BP106

    Google Scholar 

  10. Asikoğlu M, Ozguney I, Ozcan I, Orumlu O, Guneri T, Koseoğlu K, Ozkilic H (2008) The absorption of (99m)Tc–alendronate given by rectal route in rabbits. Pharm Dev Technol 13(3):213–220

    Article  Google Scholar 

  11. Ayranov M, Strezov A, Jordanova E, Piperkova E, Sergieva S (1999) Quality control and clinical application of two bone imaging 99mTc radiopharmaceuticals. J Radioanal Nucl Chem 240:349–352

    Article  CAS  Google Scholar 

  12. Sambrook PN, Rodriguez JP, Wasnich RD, Luckey MM, Kaur A, Meng L, Lombardi A (2004) Alendronate in the prevention of osteoporosis: 7-year follow-up. Osteoporos Int 15(6):483–488

    Article  CAS  Google Scholar 

  13. Biswas P, Wilton L, Shakir S (2003) Pharmacovigilance study of alendronate in England. Osteoporos Int 14:507–514

    Article  CAS  Google Scholar 

  14. Sasaki A, Boyce BF, Story B, Wright KR, Chapman M, Boyce R et al (1995) Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res 55:3551–3557

    CAS  Google Scholar 

  15. Rabbani P, Harakidas T, Bowlin G (1998) Effect of nucleoside analogue BCH-4556 on prostate cancer growth and metastases in vitro and in vivo. Cancer Res 58:3461–3465

    CAS  Google Scholar 

  16. Iguchi H, Tanaka S, Ozawa Y, Kashiwakuma T, Kimura T, Hiraga T et al (1996) An experimental model of bone metastasis by human lung cancer cells: the role of parathyroid hormone-related protein in bone metastasis. Cancer Res 56:4040–4043

    CAS  Google Scholar 

  17. Iguchi E, Onuma K, Sato K, Sato E (2001) Involvement of parathyroid hormone-related protein in experimental cachexia induced by a human lung cancer-derived cell line established from a bone metastasis specimen. Int J Cancer 94:24–27

    Article  CAS  Google Scholar 

  18. Miki T, Yano S, Hanibuchi M, Kanematsu T, Muguruma H, Sone S (2004) Parathyroid hormone-related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice. Int J Cancer 108:511–515

    Article  CAS  Google Scholar 

  19. Sikes RA, Nicholson BE, Koeneman KS, Edlund NM, Bissonette EA, Bradley MJ et al (2004) Cellular interactions in the tropism of prostate cancer to bone. Int J Cancer 110:497–503

    Article  CAS  Google Scholar 

  20. Wiesner C, Bonfil RD, Dong Z, Yamamoto H, Nabha SM, Meng H et al (2007) Heterogeneous activation of MMP-9 due to prostate cancer–bone interaction. Urology 69:795–799

    Article  Google Scholar 

  21. Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, Keller ET (2008) Prostate cancer induces bone metastasis through wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res 68:5785–5794

    Article  CAS  Google Scholar 

  22. André LBB, das Luciene GM, de Carolina AF, Natássia CRC, de Alfredo MG, Mônica CO, Valbert NC (2013) 99mTc-labeled bombesin analog for breast cancer identification. J Radioanal Nucl Chem 295(3):2083–2090

    Article  Google Scholar 

  23. Weigelt B, Bissel ML (2008) Unraveling the microenvironmental influences on the normal mammary gland and breast cancer. Semin Cancer Biol 18:311–321

    Article  CAS  Google Scholar 

  24. Ohshiba T, Miyaura C, Ito A (2003) Role of prostaglandin E produced by osteoblasts in osteolysis due to bone metastasis. Biochem Biophys Res Commun 300:957–964

    Article  CAS  Google Scholar 

  25. Yu-Ping X, Min Y, Dong-Hui P, Li-Zhen W (2011) Preparation of 131I–betulinic acid and its biodistribution in murine model of hepatocellular tumor. J Radioanal Nucl Chem 288:157–161

    Article  Google Scholar 

  26. Drishty S, Archana M, Meera V, Sharmila B (2011) Radiosynthesis and in vitro evaluation of 99mTc(CO)3-labeled folic acid derivative. J Radioanal Nucl Chem 290(1):89–93

    Article  Google Scholar 

  27. Noguera EC, Jaime A, Veliz J, Nicolini J, Ugetti R (2002) Bone scintigraphy with 99mTc–alendronate: a potential bone imaging agent in place of other bisphosphonates. The 8th congress of the World Federation of Nuclear Medicine & Biology, Abstract 142. Revista de Medicina Nuclear Alasbimn Journal 5

  28. Wahlang B, Pawar YB, Bansal AK (2011) Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur J Pharm Biopharm 77:275–282

    Article  CAS  Google Scholar 

  29. Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH et al (2006) The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA 103:7829–7834

    Article  CAS  Google Scholar 

  30. Lipton A (2010) The bone seeking property of ALD has been exploited in several ways by direct conjugation or to a cargo for both imaging and therapy of cancer implications of bone metastases and the benefits of bone-targeted therapy. Semin Oncol 37(2):S15–S29

    Article  CAS  Google Scholar 

  31. Low S, Kopecek J (2012) Targeting polymer therapeutics to bone. Adv Drug Deliv Rev 64(12):1189–1204

    Article  CAS  Google Scholar 

  32. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487

    Article  CAS  Google Scholar 

  33. Reszka AA, Halasy-Nagy JM, Masarachia PJ, Rodan GA (1999) Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase. J Biol Chem 274:34967–34973

    Article  CAS  Google Scholar 

  34. El-Mabhouh A, Angelov C, McEwan A, Jia G, Mercer J (2004) Preclinical investigations of drug and radionuclide conjugates of bisphosphonates for the treatment of metastatic bone cancer. Cancer Biother Radiopharm 19:627–640

    Article  CAS  Google Scholar 

  35. Hosain F, Spencer RP, Couthon HM, Sturtz GL (1996) Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-99m-labeled gem–bisphosphonate conjugate of methotrexate. J Nucl Med 37:105–107

    CAS  Google Scholar 

  36. Murphy A, Meléndez-Alafort L, Montoya-Molina CE, Sepúlveda-Méndez J (1997) Radiopharmacokinetic data for 99mTc–ABP—a new radiopharmaceutical for bone scanning: comparison with 99mTc–MDP. Nucl Med Biol 24(1):27–33

    Article  Google Scholar 

  37. Konsoula R, Barile FA (2005) Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells. Toxicol In Vitro 19(5):675–684

    Article  CAS  Google Scholar 

  38. Yand SF, Yao M, Zeng J, Shi ZY, Zhao LX, Dong QG (2003) Can tumor uptake Tc-99m MDP? Alasbimn J 5(19):19–24

    Google Scholar 

  39. Maestrelli F, Zerrouk N, Chemtob C, Mura P (2004) Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells. Int J Pharm 271:257–267

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The authors would like to acknowledge the support of Ege University Nuclear Medicine Department to obtain the 99mTc radionuclide.

Author information

Authors and Affiliations

  1. Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey

    Evren Gundogdu

  2. Department of Radiopharmacy, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey

    Derya Ilem-Ozdemir & Makbule Asikoglu

Authors
  1. Evren Gundogdu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derya Ilem-Ozdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Makbule Asikoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Derya Ilem-Ozdemir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gundogdu, E., Ilem-Ozdemir, D. & Asikoglu, M. In vitro incorporation studies of 99mTc–alendronate sodium at different bone cell lines. J Radioanal Nucl Chem 299, 1255–1260 (2014). https://doi.org/10.1007/s10967-013-2833-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-013-2833-z

Keywords

Search

Navigation