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Estimated background doses of [67Ga]-DTPA-USPIO in normal Balb/c mice as a potential therapeutic agent for liver and spleen cancers

Shanehsazzadeh, Saeeda,c; Oghabian, Mohammad A.a,c; Lahooti, Afsaneha; Abdollahi, Mohammadf; Abolghasem Haeri, Seyedd; Amanlou, Massoudb; Daha, Fariba J.e; Allen, Barry J.g

doi: 10.1097/MNM.0b013e328362d2fb
Original Articles

Introduction: The aim of this study was to evaluate the biodistribution of dextran-coated iron oxide nanoparticles labeled with gallium-67 (67Ga) in various organs by intravenous injection in Balb/c mice.

Methods: Ultrasmall superparamagnetic iron oxide (USPIO) was successively labeled with 67Ga-chloride after chelation with freshly prepared cyclic DTPA-dianhydride. The labeling efficiency of USPIOs labeled with 67Ga is above 98%. Sixty-five mice were killed at 13 different time points. The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The medical internal radiation dose formula was applied to extrapolate data from mouse to human and to predict the absorbed radiation dose for various organs in the human body.

Results: The biodistribution of 67Ga-USPIO in Balb/c mice showed that 75% of the injected dose accumulated in the spleen and liver 15 min after injection. These nanoparticles remained in the liver for more than 7 days after injection, whereas their clearance was very fast from other organs. Extrapolating these data to the intravenous injection of 67Ga-USPIO in humans gave an estimated absorbed dose of 36.38 mSv/MBq for the total body, and the highest effective absorbed dose was seen in the liver (32.9 mSv/MBq).

Conclusion: High uptakes of USPIO nanoparticles in the liver and spleen and their fast clearance from other tissues suggest that these nanoparticles labeled with a β-emitter radioisotope could be suitable as treatment agents for spleen and liver malignancies only if the organ tolerance dose is not exceeded.

aDepartment of Medical Physics and Biomedical Engineering, Faculty of Medicine

bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences

cResearch Center for Sciences and Technology in Medicine, Emam Hospital

dAgriculture, Medicine and Industry Research School, Nuclear Sciences and Technology Research Institute

eRadioisotope Division, Nuclear Research Center, Atomic Energy Organization of Iran, Tehran

fDepartment of Medical Physics, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

gExperimental Radiation Oncology, Cancer Pathology & Cell Biology Laboratory, School of Medicine, University of Western Sydney, New South Wales, Australia

Correspondence to Saeed Shanehsazzadeh, PhD, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran 1419733141, Iran Tel: +98 216 690 7519; fax: +98 216 658 1533; e-mail: sa27sh@gmail.com

Received March 6, 2013

Accepted May 1, 2013

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins