Evaluation of Functionalized Polysaccharide Microparticles Dosimetry for SPECT Imaging Based on Biodistribution Data of Rats
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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.
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.
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.
Animal-based human dose estimates support a future first-in-human testing of [99mTc] MP-fucoidan following IV injection.
Key wordsPreclinical Rat Polysaccharide Microparticle Absorbed dose Effective dose SPECT OLINDA/EXM OEDIPE SAAM II
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.
- 8.Cristy M, Eckerman KF (1987) Specific absorbed fractions of energy at various ages from internal photon sources. VII. Adult Male. Oak Ridge National Laboratory; Document Number ORNL/TM-8381/V7Google Scholar
- 9.International Commission on Radiological Protection (1991) 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60, Ann. ICRP 21, Pergamon PressGoogle Scholar
- 10.International Commission on Radiological Protection (2009) Adult Reference Computational Phantoms. ICRP Publication 110, Ann. ICRP 39, ElsevierGoogle Scholar
- 11.International Commission on Radiological Protection (2007) The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103, Ann. ICRP 37, ElsevierGoogle Scholar
- 12.Petitguillaume A, Bernardini M, Hadid L et al (2014) Three-dimensional personalized Monte Carlo dosimetry in 90Y resin microspheres therapy of hepatic metastases: non-tumoral liver and lungs radiation protection considerations and treatment planning optimization. J Nucl Med 55:405–413PubMedCrossRefGoogle Scholar
- 13.Pelowitz DB (2008) MCNPX user’s manual version 2.6.0 Report LA-CP-05-0369. Los Alamos National LaboratoryGoogle Scholar
- 14.Mikheev NB (1976) Radioactive colloidal solutions and suspensions for medical use. At Energ Rev 14:3–36Google Scholar
- 16.Farris EJ, Jr G, John Q (1949) The rat in laboratory investigation. Company, JB LippincottGoogle Scholar
- 19.Barrett PH, Bell BM, Cobelli C, et al. (1998) SAAM II: simulation, analysis, and modeling software for tracer and pharmacokinetic studiesGoogle Scholar
- 20.Kirschner A, Ice R, Beierwaltes W (1975) Radiation dosimetry of 131I-19-iodocholesterol: the pitfalls of using tissue concentration data, the author’s reply. J Nucl Med 16:248–249Google Scholar
- 21.Stabin MG (2008) Fundamentals of Nuclear Medicine. SpringerGoogle Scholar
- 22.International Commission on Radiological Protection (2008) Radiation dose to patients from radiopharmaceuticals—addendum 3 to ICRP Publication 53. ICRP Publication 106, Ann. ICRP 38, ElsevierGoogle Scholar
- 23.International Commission on Radiological Protection (2002) Basic anatomical and physiological data for use in radiological protection reference values. ICRP Publication 89, Ann. ICRP 32, Pergamon PressGoogle Scholar
- 26.International Commission on Radiological Protection (2008) Nuclear decay data for dosimetric calculations. ICRP Publication 107, Ann. ICRP 38, ElsevierGoogle Scholar
- 29.Crawford DJ, Richmond CR (1981) Epistemological considerations in the extrapolation of metabolic data from non-humans to humans. In: Watson E, Schlafke-Stelson A, Coffey J, Cloutier R (eds) Third International Radiopharmaceutical Dosimetry Symposium. U.S. Department of Health, Education, and Welfare, Washington, DC, pp 191–197Google Scholar
- 30.Wegst A (1981) Collection and presentation of animal data relating to internally distributed radionuclides. In: Watson E, Schlafke-Stelson A, Coffey J, Cloutier R (eds) Third International Radiopharmaceutical Dosimetry Symposium. U.S. Department of Health, Education, and Welfare, Washington, DC, pp 198–203Google Scholar
- 32.International Commission on Radiological Protection (1998) Radiation dose to patients from radiopharmaceuticals—addendum 2 to ICRP Publication 53. ICRP Publication 80, Ann. ICRP 28, PergamonGoogle Scholar