Advances in nano research

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Synthesis and radiolabeling of PEGylated dendrimer-G2-Gemifloxacin with 99mTc to Biodistribution study in rabbit

  • Mohtavinejad, Naser (Department of Radiopharmacy, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences) ;
  • Dolatshahi, Shaya (Pharm, D. Faculty of Pharmacy, Tehran University of Medical Sciences) ;
  • Amanlou, Massoud (Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences) ;
  • Ardestani, Mehdi Shafiee (Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences) ;
  • Asadi, Mehdi (Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences) ;
  • Pormohammad, Ali (Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences)
  • Received : 2020.06.07
  • Accepted : 2021.01.17
  • Published : 2021.05.25
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Abstract

Infection is one of the major mortality causes throughout the globe. Nuclear medicine plays an important role in diagnosis of deep infections such as osteomyelitis, arthritis infection, heart valve and heart prosthesis infections. Techniques such as labeled leukocytes are sensitive and selective for tracking the inflammations but they are not suitable for differentiating infection from inflammation. Anionic linear-globular dendrimer-G2 was synthesized then conjugation to gemifloxacin antibiotic. The structures were identified by FT-IR, 1H-NMR, C-NMR, LC-MS and DLS. The toxicity of gemifloxacin and dendrimer-gemifloxacin complex was compared by MTT test. Dendrimer-G2-gemifloxacin was labeled by Technetium-99m and its in-vitro stability and radiochemical purity were investigated. In-vivo biodistribution and SPECT imaging were studied in a rabbit model. Identify and verify the structure of the each object was confirmed by FT-IR, 1H-NMR, C-NMR and LC-MS, also, the size and charge of this compound were 128 nm and -3/68 mv respectively. MTT test showed less toxicity of the dendrimer-G2-gemifloxacin than free gemifluxacin (P < 0.001). Radiochemical yield was > %98. Human serum stability was 84% up to 24 h. Biodistribution study at 50 min, 24 and 48 h showed that the complex is significantly absorbed by the intestine and accumulation in the lungs and affects them, finally excreted through the kidneys, biodistribution results are consistent with results from full image means of SPECT/CT technique.

Keywords

Acknowledgement

The authors are grateful to the Research Council of Tehran University of Medical Sciences, Tehran, Iran for financial supports.

References

  1. Alavi, A. and Zhuang, H. (2001), "Finding infection-help from PET", The Lancet, 358(9291), 1386. https://doi.org/10.1016/S0140-6736(01)06491-1.
  2. Alnasser, Y., Kambhampati, S.P., Nance, E., Rajbhandari, L., Shrestha, S., Venkatesan, A., Kannan, R.M. and Kannan, S. (2018), "Preferential and increased uptake of hydroxyl terminated PAMAM dendrimers by activated microglia in rabbit brain mixed glial culture", Molecules, 23(5), 1025. https://doi.org/10.3390/molecules23051025.
  3. Arima, H., Motoyama, K. and Higashi, T. (2017), "Potential use of cyclodextrins as drug carriers and active pharmaceutical ingredients", Chem, Pharm. Bull., 65(4), 341-348. https://doi.org/10.1248/cpb.c16-00779.
  4. Benitez, A., Roca, M. and Martin-Comin, J. (2006), "Labeling of antibiotics for infection diagnosis", Q J Nucl. Med. Mol. Im., 50(2), 147-52.
  5. Blondeau, J.M. and Tillotson, G. (2007), "Gemifloxacin for the management of community-acquired respiratory tract infections", Antibiotiques, 9(3), 173-180. https://doi.org/10.1016/S1294-5501(07)91376-X.
  6. Carvalho, B.F., Albernaz, M.S. (2013), "Development of nanoradiopharmaceuticals by labeling polymer nanoparticles with tc-99m", World J. Nucl. Med.,12(1), 24-26. https://doi.org/10.4103%2F1450-1147.113946. https://doi.org/10.4103%2F1450-1147.113946
  7. Das, S.S., Hall, A.V., Wareham, D.W. and Britton, K.E. (2002), "Infection imaging with radiopharmaceuticals in the 21st century", Braz. Arch. Biol. Techn., 45(SPE), 25-37. http://doi.org/10.1590/S1516-89132002000500005.
  8. De Oliveira Freitas, L.B., de Melo Corgosinho, L., Faria, J.A.Q.A., dos Santos, V.M., Resende, J.M., Leal, A.S., Gomes, D.A. and de Sousa, E.M.B. (2017), "Multifunctional mesoporous silica nanoparticles for cancer-targeted, controlled drug delivery and imaging", Micropor. Mesopor. Mat., 242, 271-283. https://doi.org/10.1016/j.micromeso.2017.01.036.
  9. Desmonts, C., Bouthiba, M.A., Enilorac, B., Nganoa, C., Agostini, D. and Aide, N. (2020), "Evaluation of a new multipurpose whole-body CzT-based camera: Comparison with a dual-head Anger camera and first clinical images", EJNMMI physics, 7(1), 1-16. https://doi.org/10.1186/s40658-020-0284-5.
  10. Farkas, R., Siwowska, K., Ametamey, S.M., Schibli, R., van der Meulen, N.P. and Muller, C. (2016), "64Cu-and 68Ga-based PET imaging of folate receptor-positive tumors: Development and evaluation of an albumin-binding NODAGA-folate", Mole. Pharmaceutics, 13(6), 1979-1987. https://doi.org/10.1021/acs.molpharmaceut.6b00143.
  11. Ghaffari, M., Dehghan, G., Abedi-Gaballu, F., Kashanian, S., Baradaran, B., Dolatabadi, J.E.N. and Losic, D. (2018), "Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting", Eur. J. Pharm. Sci., 122, 311-330. https://doi.org/10.1016/j.ejps.2018.07.020.
  12. Gothwal, A., Malik, S., Gupta, U. and Jain, N.K. (2020), "Toxicity and biocompatibility aspects of dendrimers", Pharmaceut. Applicat. Dendrimers, 55(11), 251-274. https://doi.org/10.1016/B978-0-12-814527-2.00011-1.
  13. Govaert, G.A.M. and Glaudemans, A.W. (2016), "Nuclear medicine imaging of posttraumatic osteomyelitis", Eur. J. Trauma. Emergency Surg., 42(4), 397-410. https://doi.org/10.1007/s00068-016-0647-8.
  14. Grant, J., Naeim, M., Lee, Y., Miya, D., Kee, T. and Ho, D. (2019), "Engineering multifunctional nanomedicine platforms for drug delivery and imaging", In: Nanotheranostics for Cancer Applications, pp. 319-344, Springer, Cham. https://doi.org/10.1007/978-3-030-01775-0_14.
  15. Hall, A.V., Solanki, K.K., Vinjamuri, S., Britton, K.E. and Das, S.S. (1998), "Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection", J. Clin. Pathol., 51(3), 215-219. http://doi.org/10.1136/jcp.51.3.215.
  16. Jain, S., Krishna Cherukupalli, S. and Mahmood, A. (2019), "Emerging nanoparticulate systems: Preparation techniques and stimuli responsive release characteristics", J. Appl. Pharm. Sci, 9(8), 130-143. https://doi.org/10.7324/JAPS.2019.90817.
  17. Karthikeyan, R., Karempudi, B., Rasheed, S. and Vijayaraj, P. (2012), "Dendritic architechture for the delivery of antibacterial agent against resistant producing strains", Cent. Euro. J. Exp. Bio., 1, 45-48.
  18. Khosroshahi, A.G., Amanlou, M., Sabzevari, O., Daha, F.J., Aghasadeghi, M.R., Ghorbani, M., Ardestani, M.S., Alavidjeh, M.S., Sadat, S.M., Pouriayevali, M.H. and Mousavi, L. (2013), "A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging", Curr. Med. Chem., 20(1), 123-133. https://doi.org/10.2174/0929867311302010012
  19. Kung, M.P., Stevenson, D.A., Plossl, K., Meegalla, S.K., Beckwith, A., Essman, W.D., Mu, M., Lucki, I. and Kung, H.F. (1997), "[99mTc] TRODAT-1: A novel technetium-99m complex as a dopamine transporter imaging agent", Eur. J. Nucl. Med., 24(4), 372-380. https://doi.org/10.1007/BF00881808.
  20. Lambrecht, F.Y. (2011), "Evaluation of 99mTc-labeled antibiotics for infection detection", Annal. Nucl. Med., 25(1), 1-6. https://doi.org/10.1007/s12149-010-0417-3.
  21. Li, C., Cao, X., Ma, Z., Sun, X., Hu, F. and Wang, L. (2018), "Effect of pre-surgery assessments on the prognosis of patients received extracranial-intracranial bypass surgery", Restor. Neurol. Neuros., 36(5), 593-604. https://doi.org/10.3233/RNN180848.
  22. Lupetti, A., Welling, M.M., Pauwels, E.K. and Nibbering, P.H. (2003), "Radiolabelled antimicrobial peptides for infection detection", Lancet Infect. Dis., 3(4), 223-229. https://doi.org/10.1053/j.semnuclmed.2017.11.003.
  23. Madavan, R. and Balaraman, S. (2017), "Investigation on effects of different types of nanoparticles on critical parameters of nano-liquid insulation systems", J. Mol. Liq., 230, 437-444. https://doi.org/10.1109/ICDL.2019.8796708.
  24. Makinen, T.J., Lankinen, P., Poyhonen, T., Jalava, J., Aro, H.T. and Roivainen, A. (2005), "Comparison of 18 F-FDG and 68 Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus", Eur. J. Nucl. Med. Mol. I., 32(11), 1259-1268. https://doi.org/10.1007/s00259-005-1841-9.
  25. Magneson, G.R. and Orahood, R.C. (2016), "Compositions for radiolabeling diethylenetriaminepentaacetic acid (DTPA)-dextran", U.S. Patent, 9, 439, 985.
  26. Miyashita, H., Nakahara, T., Asoda, S., Kameyama, K., Kawaida, M., Enomoto, R., Shiba, H., Jinzaki, M., Kawana, H. and Nakagawa, T. (2019), "Clinical value of 3D SPECT/CT imaging for assessing jaw bone invasion in oral cancer patients", J. Cranio-Maxill. Surg., 47(7), 1139-1146. https://doi.org/10.1016/j.jcms.2019.03.013.
  27. Mohtavinejad, N., Amanlou, M., Bitarafan-Rajabi, A., Pormohammad, A. and Ardestani, M.S. (2020), "Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6, Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region", Bioorg. Chem., 45(6), 10373. https://doi.org/10.1016/j.bioorg.2020.103731.
  28. Okarvi, S.M. (2004), "Erratum: Peptide-based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseases", Med. Res. Rev., 24(5), 685-686. https://doi.org/10.1002/med.20015.
  29. Pakos, E.E., Trikalinos, T.A., Fotopoulos, A.D. and Ioannidis, J.P. (2007), "Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte scintigraphy with 99mTclabeled monoclonal antibodie-A meta-analysis", Radiology, 242(1), 101-108. https://doi.org/10.1148/radiol.2421052011.
  30. Raza, M.A., Kanwal, Z., Rauf, A., Sabri, A.N., Riaz, S. and Naseem, S. (2016), "Size-and shape-dependent antibacterial studies of silver nanoparticles synthesized by wet chemical routes", Nanomaterials, 6(4), 74. https://doi.org/10.3390/nano6040074.
  31. Roohi, S., Mushtaq, A. and Malik, S.A. (2005), "Synthesis and biodistribution of 99mTc-Vancomycin in a model of bacterial infection", Radiochim. Acta., 93(7), 415-418. https://doi.org/10.1524/ract.2005.93.7.415.
  32. Roohi, S., Mushtaq, A., Jehangir, M. and Malik, S.A. (2006), "Synthesis, quality control and biodistribution of 99mTcKanamycin", J. Radioanal. Nucl. Ch., 267(3), 561-566. https://doi.org/10.1007/s10967-006-0087-8.
  33. Sadeek, S.A. and El-Hamid, S.M.A. (2016), "Synthesis, spectroscopic, thermal analysis and in vitro biological properties of some new metal complexes with gemifloxacin and 1, 10-phenanthroline", J. Therm. Anal. Calorim., 124(1), 547-562. https://doi.org/10.1007/s10973-015-5057-3.
  34. Shahzad, S., Qadir, M.A., Rasheed, R. and Ahmed, M. (2019), "Synthesis of 99mTc-gemifloxacin freeze dried kits and their biodistribution in Salmonella typhi, Pseudomonas aeruginosa and Klebsiella pneumoniae", Arab, J. Chem., 12(5), 664-670. https://doi.org/10.1016/j.arabjc.2015.10.002.
  35. Sharma, R., Kim, S.Y., Sharma, A., Zhang, Z., Kambhampati, S.P., Kannan, S. and Kannan, R.M. (2017), "Activated microglia targeting dendrimer-minocycline conjugate as therapeutics for neuroinflammation", Bioconjugate Chem., 28(11), 2874-2886. https://doi.org/10.1021/acs.bioconjchem.7b00569.
  36. Signore, A. and Glaudemans, A.W. (2011), "The molecular imaging approach to image infections and inflammation by nuclear medicine techniques", Annal. Nucl. Med., 25(10), 681-700. https://doi.org/10.1007/s12149-011-0521-z.
  37. Solanki, K.K., Bomanji, J., Siraj, Q., Small, M. and Britton, K.E. (1993), "99mTc Infecton-A new class of radiopharmaceutical for imaging infection", J. Nucl. Med., 34, 119A.
  38. Sonvico, F., Clementino, A., Buttini, F., Colombo, G., Pescina, S., Staniscuaski Guterres, S., Raffin Pohlmann, A. and Nicoli, S. (2018), "Surface-modified nanocarriers for nose-to-brain delivery: from bioadhesion to targeting", Pharmaceutics, 10(1), 34. https://doi.org/10.3390/pharmaceutics10010034.
  39. Torres, L., Alves, V., Oliveira, A. and Pereira, J. (2018), "Fab'fragments of 99mTc-labeled anti-granulocyte monoclonal antibodies in vascular graft infection", Annal. Nucl. Med., 15(10), 621-627.
  40. Yurt Lambrecht, F., Yilmaz, O., Unak, P., Seyitoglu, B., Durkan, K. and Baskan, H. (2008), "Evaluation of 99mTc- Cefuroxime axetil for imaging of inflammation", J. Radioanal. Nucl. Chem., 277(2), 491-494. https://doi.org/10.1007/s10967-007-7111-5.