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Radiolabeling of Preformed Niosomes with [99mTc]: In Vitro Stability, Biodistribution, and In Vivo Performance

  • Ameneh Almasi
  • Soraya Shahhosseini
  • Azadeh Haeri
  • Fariba Johari Daha
  • Parham Geramifar
  • Simin Dadashzadeh
Research Article
  • 33 Downloads

Abstract

Nanocarriers radiolabeled with [99mTc] can be used for diagnostic imaging and radionuclide therapy, as well as tracking their pharmacokinetic and biodistribution characteristics. Due to the advantages of niosomes as an ideal drug delivery system, in this study, the radiolabeling procedure of niosomes by [99mTc]-HMPAO complexes was investigated and optimized. Glutathione (GSH)-loaded niosomes were prepared using a thin-film hydration method. To label the niosomes with [99mTc], the preformed GSH-loaded niosomes were incubated with the [99mTc]-HMPAO complex and were characterized for particle size, size distribution, zeta potential, morphology, and radiolabeling efficiency (RE). The effects of GSH concentration, incubation time, incubation temperature, and niosomal composition on RE were investigated. The biodistribution profile and in vivo SPECT/CT imaging of the niosomes and free [99mTc]-HMPAO were also studied. Based on the results, all vesicles had nano-sized structure (160–235 nm) and negative surface charge. Among the different experimental conditions that were tested, including various incubation times, incubation temperatures, and GSH concentrations, the optimum condition that resulted in a RE of 92% was 200-mM GSH and 15-min incubation at 40°C. The in vitro release study in plasma showed that about 20% of radioactivity was released after 24 h, indicating an acceptable radiolabeling stability in plasma. The biodistribution of niosomes was clearly different from the free radiolabel. Niosomes carrying radionuclide were successfully used for tracking the in vivo disposition of these carriers and SPECT/CT imaging in rats. Furthermore, biodistribution studies in tumor-bearing mice revealed higher tumor accumulation of the niosomal formulation as compared with [99mTc]-HMPAO.

KEY WORDS

radiolabeling biodistribution niosome SPECT/CT imaging [99mTc]-HMPAO 

Abbreviations

[99mTc]

Technetium-99m

AFM

Atomic force microscopy

CHOL

Cholesterol

CT

Computed tomography

DTPA

Diethylene triamine pentaacetic acid

GSH

Glutathione

HMPAO

Hexamethyl propylene amine oxime

IT

Isomeric transition

MPS

Mononuclear phagocyte system

PBS

Phosphate buffered saline

RE

Radiolabeling efficiency

SEC

Size-exclusion chromatography

SEM

Scanning electron microscopy

SPECT

Single-photon emission computed tomography

T60

Tween 60

TLC

Thin-layer chromatography

Notes

Funding Information

This research was supported by a grant from Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.

Compliance with Ethical Standards

All animal studies were approved by the ethics committee for animal experiments at the Shahid Beheshti University of Medical science, Tehran, Iran.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Nanotechnology, School of PharmacyShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy and Protein Technology Research CenterShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Radiation Application Research SchoolNuclear Science and Technology Research Institute (NSTRI)TehranIran
  4. 4.Research Center for Nuclear MedicineTehran University of Medical SciencesTehranIran
  5. 5.Pharmaceutical Sciences Research CenterShahid Beheshti University of Medical SciencesTehranIran

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