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Molecular Imaging and Biology

, Volume 17, Issue 4, pp 504–511 | Cite as

Evaluation of Functionalized Polysaccharide Microparticles Dosimetry for SPECT Imaging Based on Biodistribution Data of Rats

  • Aurélie DesbréeEmail author
  • Thomas Bonnard
  • Eric Blanchardon
  • Anne Petiet
  • Didier Franck
  • Cedric Chauvierre
  • Catherine Le Visage
Research Article

Abstract

Purpose

Technetium-99 m (Tc-99 m)-labelled microparticles, functionalized with fucoidan to present a high affinity for P-Selectin, or [99mTc] MP-fucoidan, were developed as a novel SPECT radiotracer for abdominal aortic aneurysm (AAA). As a prerequisite step forwards a clinical trial, the biodistribution and dosimetry of these [99mTc] MP-fucoidan microparticles were performed in rats in order to estimate the absorbed and effective dose in humans.

Procedures

Microparticles with a maximum hydrodynamic diameter of 4 μm were obtained by crosslinking polysaccharides dextran and pullulan. They were functionalized with fucoidan then radiolabelled with Tc-99 m. A mean labelling efficiency of 92 ± 1 % was measured. [99mTc] MP-fucoidan (43 ± 2 MBq) was injected to 24 rats via the penis vein. Rats were euthanized at 30, 60, 120 and 240 min after injection (4 rats at each time point). Samples of each organ, as well as the injected microparticle suspensions, were aliquoted for counting. Four animals were sacrificed for blood clearance studies and four were sacrificed for image analysis and quantification of the cortical, medullary, papillary kidney, and pelvis uptake. A compartmental model was realised using SAAM II and organ data were fitted. The area under the curve was then used to compute the residence times in each rat organs and converted to human residence time values. Absorbed and effective human doses in organs were estimated using (1) the OLINDA/EXM 1.1 software with the hermaphroditic mathematical phantoms and (2) the OEDIPE software associated to the MCNPX Monte Carlo code and the ICRP reference computational male and female phantoms, using the updated tissue weighting factors in the ICRP Publication 103.

Results

The highest human residence times were found in the liver, kidneys, and urinary bladder wall. The largest doses were found in the kidneys and then in the urinary bladder wall and liver. The human effective doses were 6.06 μSv/MBq for the hermaphroditic mathematical phantom and 5.95 μSv/MBq for the ICRP adult reference computational phantom.

Conclusions

Animal-based human dose estimates support a future first-in-human testing of [99mTc] MP-fucoidan following IV injection.

Key words

Preclinical Rat Polysaccharide Microparticle Absorbed dose Effective dose SPECT OLINDA/EXM OEDIPE SAAM II 

Notes

Acknowledgments

This research was supported by the Institut de Radioprotection et de Sûreté Nucléaire, Inserm and University Paris 13. T. Bonnard is a recipient of the French Ministry of Higher Education and Research Scholarship (ED Galilée, University Paris 13). The authors would like to acknowledge the financial support from ANR-12-EMMA-0020-01 “MicroSound”, FP7 NMP-LA-2012-309820 “Nanoathero” and the Centre d’explorations fonctionnelles—Imagerie (CEFI, institut Claude Bernard).

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© World Molecular Imaging Society 2014

Authors and Affiliations

  • Aurélie Desbrée
    • 1
    Email author
  • Thomas Bonnard
    • 2
    • 4
  • Eric Blanchardon
    • 1
  • Anne Petiet
    • 3
  • Didier Franck
    • 1
  • Cedric Chauvierre
    • 2
    • 4
  • Catherine Le Visage
    • 2
    • 4
    • 5
  1. 1.Institut de Radioprotection et de Sûreté NucléaireService de Dosimétrie InterneFontenay-aux-RosesFrance
  2. 2.Inserm, U1148—Laboratory for Vascular Translational ScienceX. Bichat HospitalParisFrance
  3. 3.IFR 02, UFR de Médecine, site BichatUniversité Paris DiderotParisFrance
  4. 4.Institut GaliléeUniversité Paris 13VilletaneuseFrance
  5. 5.INSERM, U791Center for Osteoarticular and Dental Tissue Engineering, Dental SchoolNantesFrance

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