title: Evaluation of Functionalized Polysaccharide Microparticles Dosimetry for SPECT Imaging Based on Biodistribution Data of Rats.
abstract: OBJECTIVE
  Technetium-99 m (Tc-99 m)-labelled microparticles, functionalized with fucoidan to present a high affinity for P-Selectin, or [(99m)Tc] 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 [(99m)Tc] MP-fucoidan microparticles were performed in rats in order to estimate the absorbed and effective dose in humans.
  
  
  METHODS
  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. [(99m)Tc] 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 [(99m)Tc] MP-fucoidan following IV injection.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Service de Dosimétrie Interne, 31 avenue de la Division Leclerc, 92260, Fontenay-aux-Roses, France, aurelie.desbree@irsn.fr.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Desbrée
authors.forename: Thomas
authors.initials: T
authors.lastname: Bonnard
authors.forename: Eric
authors.initials: E
authors.lastname: Blanchardon
authors.forename: Anne
authors.initials: A
authors.lastname: Petiet
authors.forename: Didier
authors.initials: D
authors.lastname: Franck
authors.forename: Cedric
authors.initials: C
authors.lastname: Chauvierre
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Visage
mesh_terms: D000818:Animals; D007668:Kidney / Q000378:metabolism; D008297:Male; D015233:Models, Statistical; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D011874:Radiometry / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D011134:Polysaccharides; D013667:Technetium; C007789:fucoidan