Skip to main content
SpringerLink
Log in

Preparation of a 99mTc-labeled graft polymer and its in vitro and in vivo evaluation

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

Abstract

The aim of this study is the synthesis of a novel 99mTc-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was prepared and labeled with 99mTc. The radiochemical yield of approximately the 99mTc-labeled compound amounted to 97 ± 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Yang B, Zhang F, Yuan WL, Du L, Jiang XJ, Javadzadeh Y, Araneda R (2021) Preparation of isorhamnetin nanoparticles and their targeting efficiency to nasopharynx cancer. J Nanosci Nanotechnol 21:1293–1299

    Article  CAS  PubMed  Google Scholar 

  2. Zheng YY, Hong XQ, Wang JT, Feng LB, Fan TJ, Guo R, Zhang H (2021) 2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges. Adv Healthc Mater 10(7):2001743

    Article  CAS  Google Scholar 

  3. Rabiee N, Ahmadi S, Fatahi Y, Rabiee M, Bagherzadeh M, Dinarvand R, Bagheri B, Zarrintaj P, Saeb MR, Webster TJ (2020) Nanotechnology-assisted microfluidic systems: from bench to bedside. Nanomedicine 16:237–258

    Article  CAS  Google Scholar 

  4. Hayran O (2019) New medical technologies and ethical issues. J Biotechnol 3:54–60

    Google Scholar 

  5. Sahoo SK, Parveen S, Panda JJ (2007) The present and future of nanotechnology in human health care. Nanomed-Nanotechnol 3:20–31

    Article  CAS  Google Scholar 

  6. Inanan T, Tüzmen N, Akgöl S, Denizli A (2016) Selective cholesterol adsorption by molecular imprinted polymeric nanospheres and application to GIMS. Int J Biol Macromol 92:451–460

    Article  CAS  PubMed  Google Scholar 

  7. Vermeulen K, Vandamme M, Bormans G, Cleeren F (2019) Design and challenges of radiopharmaceuticals. Seminars in nuclear medicine 49(5):339–356

    Article  PubMed  Google Scholar 

  8. Szabados L, Savoure A (2010) Proline: a multifunctional amino acid. Trends Plant Sci 15:89–97

    Article  CAS  PubMed  Google Scholar 

  9. Sukumaran J, Hanefeld U (2005) Enantioselective C-C bond synthesis catalysed by enzymes. Chem Soc Rev 34:530–542

    Article  CAS  PubMed  Google Scholar 

  10. Faber K (2000) Biotransformations in Organic Chemistry. Springer, New York

    Book  Google Scholar 

  11. Saboury B, Morris M, Cao Q (2018) Determination of cis-4-[18F][1]fluoro-L-proline (18F-FP) normal biodistribution in experiments optimized for hepatic uptake using dynamic and static PET/CT imaging. J Nucl Med 59:1235

    Google Scholar 

  12. Ponrasu T, Jamuna S, Mathew A, Madhukumar KN, Ganeshkumar M, Iyappan K, Suguna L (2013) Efficacy of L-proline administration on the early responses during cutaneous wound healing in rats. Amino Acids 45:179–189

    Article  CAS  PubMed  Google Scholar 

  13. Bhat A, Smith B, Dinu CZ, Guiseppi-Elie A (2019) Dataset on hydrophobicity indices and differential scanning calorimetry thermograms for poly (HEMA)-based hydrogels. Data in brief. 24:103891

    Article  PubMed  PubMed Central  Google Scholar 

  14. Andrade, J. D. (Ed.) (1976) Hydrogels for medical and related applications. American Chemical Society

  15. Montheard JP, Chatzopoulos M, Chappard D (1992) 2-hydroxyethyl methacrylate (HEMA): chemical properties and applications in biomedical fields. Polym Rev (Phila Pa) 32:1–34

    Google Scholar 

  16. Ratner BD, Hoffman AS, Schoen FJ (2004) Orthopedic materials. Application of materials in medicine, biology and artificial organs. Biomaterials Science: An Introduction to Materials in Medicine. Elsevier, London

  17. Banik BL, Fattahi P, Brown JL (2016) Polymeric nanoparticles: the future of nanomedicine. Wiley interdiscip Rev Nanomed Nanobiotechnol 8:271–299

    Article  PubMed  Google Scholar 

  18. Elsabahy M, Wooley KL (2012) Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 41:2545–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Crisponi G, Nurchi VM, Lachowicz JI (2017) Toxicity of nanoparticles: etiology and mechanisms. In: Grumezescu AM (ed) Antimicrobial Nanoarchitectonics. Elsevier, Bucharest

    Google Scholar 

  20. Avcıbaşı U, Avcıbaşı N, Akalın HA, Ediz M, Demiroğlu H, Gümüşer FG, Özçalışkan E, Türkcan C, Uygun DA, Akgöl S (2013) Synthesis and biodistribution of novel magnetic poly(hema-aph) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy. J Nanopart Res 15:2021

    Article  CAS  Google Scholar 

  21. Toprak A, Görgün C, Kuru Cİ, Türkcan C, Uygun M, Akgöl S (2015) Boronate affinity nanoparticles for RNA isolation. Mat Sci Eng C Mater Biol Appl 50:251–256

    Article  CAS  Google Scholar 

  22. Kuru Cİ, Türkcan C, Uygun M, Okutucu B, Akgöl S (2016) Preparation and characterization of silanized poly (HEMA) nanoparticles for recognition of sugars. Artif Cells Nanomed Biotechnol 44:835–841

    CAS  PubMed  Google Scholar 

  23. Akgöl S, Kaçar Y, Özkara S, Yavuz H, Denizli A, Arıca MY (2001) Immobilization of catalase via adsorption onto l-histidine grafted functional pHEMA based membrane. J Mol Catal B-Enzym 15:197–206

    Article  Google Scholar 

  24. Bakan B, Kayhan CT, Karayildirim CK, Dağdeviren M, Gülcemal S, Yıldırım Y, Akgöl S, Yavaşoğlu NUK (2019) Synthesis, characterization, toxicity and in vivo imaging of lysine graft polymeric nanoparticles. J Polym Res 26:239

    Article  CAS  Google Scholar 

  25. Avcıbaşı U, Ateş B, Ünak P, Gümüşer FG, Gülcemal S, Ol KK, Akgöl S, Tekin V (2019) A novel radiolabeled graft polymer: investigation of the radiopharmaceutical potential using albino wistar rats. Appl Radıat Isot. 154:108872

    Article  PubMed  CAS  Google Scholar 

  26. Bangs LB (1989) Uniform latex particles. 41 th National meeting, American Association for Clinical Chemistry, Seragen Diagnostics, Indianapolis

  27. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  28. Maron DM, Ames BN (1983) Revised methods for the salmonella mutagenicity test. Mutat Res 113:173–215

    Article  CAS  PubMed  Google Scholar 

  29. Florence C, Stanley P, Zemke R (1997) Occupational therapy for independent-living older adults: a randomized controlled trial. JAMA 278(16):1321–1326

    Article  Google Scholar 

  30. Bacterial reverse mutation test ASTM‐F756‐00 (2013) Standard practice for assessment of hemolytic properties of materials

  31. Parnham MJ, Wetzig H (1993) Toxicity screening of liposomes. Chem Phys Lipids 64:63–274

    Article  Google Scholar 

  32. Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomater 24:1121–1131

    Article  CAS  Google Scholar 

  33. Xiong Y, Jiang W, Shen Y, Li H, Sun C, Ouahab J, Tu J (2012) A poly (γ, L-glutamic acid)-citric acid based nanoconjugate for cisplatin delivery. Biomater 33:7182–7193

    Article  CAS  Google Scholar 

  34. Grabinski C, Hussain S, Lafdi K, Braydich-Stolle L (2007) Effect of particle dimension on biocompatibility of carbon nanomaterials. Carbon 45:2828–2835

    Article  CAS  Google Scholar 

  35. Couvreur P, Kante B, Grislain L, Roland M, Speiser P (1982) Toxicity of polyalkylcyanoacrylate nanoparticles II: doxorubicin-loaded nanoparticles. J Pharm Sci 71:790–792

    Article  CAS  PubMed  Google Scholar 

  36. Hussain SM, Hess KL, Gearhart JM, Geiss KT (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983

    Article  CAS  PubMed  Google Scholar 

  37. Voigt N, Henrich-Noack P, Kockentiedt S, Hintz W, Tomas J, Sabel BA (2014) Toxicity of polymeric nanoparticles in vivo and in vitro. J Nanopart Res 16:2379

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Monteiro-Riviere NA, Inman AO, Zhang LW (2009) Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. Toxicol Appl Pharmacol 234:222–235

    Article  CAS  PubMed  Google Scholar 

  39. Türkmen D, Bereli N, Çorman ME, Shaikh H, Akgöl S, Denizli A (2014) Molecular imprinted magnetic nanoparticles for controlled delivery of mitomycin C. Artif Cell Nanomed Biotechnol 42:316–322

    Article  CAS  Google Scholar 

  40. Roointan A, Farzanfar J, Mohammadi-Samani S, Behzad-Behbahani A, Farjadian F (2018) Smart pH responsive drug delivery system based on poly (HEMA-co-DMAEMA) nanohydrogel. Int J Pharm 552:301–311

    Article  CAS  PubMed  Google Scholar 

  41. Saraei M, Sarvari R, Massoumi B, Agbolaghi S (2019) Co-delivery of methotrexate and doxorubicin via nanocarriers of star-like poly (DMAEMA-block-HEMA-block-AAc) terpolymers. Polym Int 68:1795–1803

    Article  CAS  Google Scholar 

  42. Kumar SSD, Surianarayanan M, Vijayaraghavan R, Mandal AB, Macfarlane DR (2014) Curcumin loaded poly (2-hydroxyethyl methacrylate) nanoparticles from gelled ionic liquid–In vitro cytotoxicity and anti-cancer activity in SKOV-3 cells. Eur J Pharm Sci 51:34–44

    Article  CAS  PubMed  Google Scholar 

  43. Fröhlich E (2012) The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomed 7:5577

    Article  Google Scholar 

  44. Louro H, Bettencourt A, Gonçalves LM (2015) M. Nanotechnology applications for tissue engineering. Nanotechnology Applications for Tissue Engineering. Elsevier, New York

  45. Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE (2008) Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol Pharm 5:487–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen LQ, Fang L, Ling J, Ding CZ, Kang B, Huang CZ (2015) Nanotoxicity of silver nanoparticles to red blood cells: size dependent adsorption, uptake, and hemolytic activity. Chem Res Toxicol. 28(3):501–509. https://doi.org/10.1021/tx500479m

    Article  CAS  PubMed  Google Scholar 

  47. Slowing II, Wu CW, Vivero-Escoto JL, Lin VS (2009) Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells. Small 5(1):57–62. https://doi.org/10.1002/smll.200800926

    Article  CAS  PubMed  Google Scholar 

  48. Lin YS, Haynes CL (2010) Impacts of mesoporous silica nanoparticle size, pore ordering, and pore integrity on hemolytic activity. J Am Chem Soc 132:4834–4842

    Article  CAS  PubMed  Google Scholar 

  49. Kim D, El-Shall H, Dennis D, Morey T (2005) Interaction of PLGA nanoparticles with human blood constituents. Coll Surf B Biointerfaces 40:83–91

    Article  CAS  Google Scholar 

  50. Kim TH, Nah JW, Cho MH, Park TG, Cho CS (2006) Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles. J Nanosci Nanotechnol 6:2796–2803

    Article  CAS  PubMed  Google Scholar 

  51. Dekie L, Toncheva V, Dubruel P, Schact EH, Barrett L, Seymour LW (2000) Poly-L-glutamic acid derivatives as vectors for gene therapy. J Control Release 65:187–202

    Article  CAS  PubMed  Google Scholar 

  52. Huang X, Teng X, Chen D, Tang F, He J (2010) The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomater 31:438–448

    Article  CAS  Google Scholar 

  53. Pliska V, Testa B, Van de Waterbeemd H (1996) Lipophilicity and biological activity. In: Mannhold R, Kubinyi H, Timmerman H (eds) Lipophilicity in Drug Action and Toxiocology. VCH, New York, NY, pp 22–26

    Chapter  Google Scholar 

  54. Phillips R, Karnofsky DA, Hamilton LD, Nickson JJ (1954) Roentgen therapy of hepatic metastases. Am J Roentgenol 71:826–834

    CAS  Google Scholar 

  55. Ingold JA, Reed GB, Kaplan HS (1965) Radiation hepatitis. Am J Roentgenol 93:200–208

    CAS  Google Scholar 

  56. Wong Hee Kam S, Huguet F (2010) Normal tissue tolerance to external beam radiation therapy: kidney. Cancer Radiother 14:340–343

    Article  CAS  PubMed  Google Scholar 

  57. Kumar R, Roy I, Ohulchanskky TY, Vathy LA, Bergey EJ, Sajjad M, Prasad PN (2010) In vivo biodistribution and clearance studies using multimodal ORMOSIL nanoparticles. ACS Nano 4:699–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. İçhedef Ç, Teksöz S, Ünak PE, Medine Eİ, Ertay T, Bekiş R (2012) Preparation and characterization of radiolabeled magnetic nanoparticles as an imaging agent. J Nanopart Res 14:1077

    Article  CAS  Google Scholar 

  59. Alexiou C, Bergemann C, Schmid R, Hulin P, Schmidt A, Jurgons R, Arnold W, Parak FG (2002) Enrichment and biodistribution of a magnetically targeted drug carrier. Eur Cell Mater 3:135–137

    Google Scholar 

  60. Kilcar AY, Muftuler FZB, Enginar H, Tekin V, Medine EI, Unak P (2004) Synthesis, characterization and biodistribution of 99mTc-Bioquin-HMPAO (99mTc-BH) as a novel brain imaging agent. J Radioanal Nucl Chem 302:563–573

    Article  CAS  Google Scholar 

  61. Liu M, Zheng Y, Avcibasi U, Liu S (2016) Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2 = cyclohexanedione dioxime) as potential radiotracers for heart imaging. Nucl Med Biol. 43:732–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Demiroğlu H, Topal G, Parlak Y, Gümüşer FG, Türköz EU, Tekin V, Ateş B, Ünak P, Avcıbaşı U (2018) Radiosynthesis and biodistribution of 99mTc- trimethoprim: a novel radiolabeled antibiotic for bacterial infection imaging using experimental animals. Kafkas Univ Vet Fak Derg 24:393–400

    Google Scholar 

  63. Babak S, Morris M, Cao Q (2018) Determination of cis-4-[18F][1]fluoro-L-proline (18F-FP) normal biodistribution in experiments optimized for hepatic uptake using dynamic and static PET/CT imaging. J Nucl Med 59(1):1235–1242

    Google Scholar 

  64. Rao V, Guan B, Mutton LN, Bieberich CJ (2012) Proline-mediated proteasomal degradation of the prostate-specific tumor suppressor NKX31. J Biol Chem. 287(43):36331–36340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Austin-Seymour MM, Chen GT, Castro JR, Saunders WM, Pitluck S, Woodruff KH, Kessler M (1986) Dose volume histogram analysis of liver radiation tolerance. Inr J Radiation Oncology Biol Phys 12(1):31–35

    Article  CAS  Google Scholar 

  66. Dawson LA, Kavanagh BD, Paulino AC, Das SK, Miften M, Li XA, Schultheiss TE (2010) Radiation-associated kidney injury. Inr J Radiation Oncology Biol Phys 76(3):108–115

    Article  Google Scholar 

  67. Setchelll BP (1986) The movement of fluids and substances in the testis. Aust. 1. BioI Sci 39:193–207

    Google Scholar 

Download references

Acknowledgements

The authors are thankful for the financial support from the Manisa Celal Bayar University Coordination Unit of Scientific Research Projects (BAP) (Project number: 2017-016). We thank to Buket Ateş for the technical assistance during the animal experiments. We also thank Norma R. de Yagcier and Mahdi Rajabimovahed for reviewing our study as native English speakers.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Art and Science, Manisa Celal Bayar University, 45140, Manisa, Turkey

    Uğur Avcıbaşı, Taner Türkyarar & Ayşegül Karadağ

  2. Department of Biology, Faculty of Science, Ege University, 35100, İzmir, Turkey

    Buket Bakan & Nefise Ülkü Karabay Yavaşoğlu

  3. Department of Chemistry, Faculty of Science, Dokuz Eylül University, 35390, İzmir, Turkey

    Kevser Kuşat

  4. Department of Biochemistry, Faculty of Science, Ege University, 35100, İzmir, Turkey

    Sinan Akgöl

  5. Department of Chemistry, Faculty of Science, Ege University, 35100, İzmir, Turkey

    Derya Gülcemal

  6. Institute of Nuclear Sciences, Department of Nuclear Applications, Ege University, 35100, Bornova, İzmir, Turkey

    Volkan Tekin & Fazilet Zümrüt Biber Müftüler

  7. Department of Nuclear Medicine, School of Medicine, Manisa Celal Bayar University, Manisa, Turkey

    Gökcen Topal, Yasemin Parlak & Fikriye Gül Gümüşer

  8. Department of Molecular Biology and Genetics, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey

    Buket Bakan

Authors
  1. Uğur Avcıbaşı
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taner Türkyarar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayşegül Karadağ
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Buket Bakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nefise Ülkü Karabay Yavaşoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevser Kuşat
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sinan Akgöl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Derya Gülcemal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Volkan Tekin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fazilet Zümrüt Biber Müftüler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gökcen Topal
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yasemin Parlak
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fikriye Gül Gümüşer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uğur Avcıbaşı.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Avcıbaşı, U., Türkyarar, T., Karadağ, A. et al. Preparation of a 99mTc-labeled graft polymer and its in vitro and in vivo evaluation. J Radioanal Nucl Chem 329, 511–525 (2021). https://doi.org/10.1007/s10967-021-07817-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-021-07817-6

Keywords

Search

Navigation