Pharmacokinetics and radiation dosimetry of ^99mTc-3PRGD₂ in healthy individuals: A pilot study

Pharmacokinetics and radiation dosimetry of 99m Tc-3PRGD 2 in healthy individuals: A pilot study 1 first-author 1 1 1 2 3 1 corresp Corresponding author. E-mail address: wangqing@tom.com Corresponding author. E-mail address: wangqing@tom.com wangqing@tom.com China-Japan Union Hospital, Jilin University, Changchun 130033, China China-Japan Union Hospital, Jilin University, Changchun 130033, China Medical Isotopes Research Center, Peking University, Beijing 100191, China Medical Isotopes Research Center, Peking University, Beijing 100191, China Department of Nuclear Medicine, People's Hospital of Shenzhen, Shenzhen 518020, China Department of Nuclear Medicine, People's Hospital of Shenzhen, Shenzhen 518020, China 99m Tc-3PRGD 2 is a new SPECT radiotracer for several tumor imaging with high uptake where integrin α v β 3 is highly expressed. This pilot study was to assess the safety, biodistribution and radiation dosimetry of 99m Tc-3PRGD 2 in healthy volunteers. The 10 healthy male volunteers were injected with 99m Tc-3PRGD 2 (786.7±55.8 MBq, 19.1–24.2 mCi). Baseline measurements of vital signs, laboratory safety tests and 12-lead electrocardiogram were recorded before and after injection. Blood and urine samples were collected and radiation counts were obtained at various time points. Whole-body scans and ROIs of identified organs were used for visual analysis and estimating the radiation dosimetry. No adverse reactions were found during the study. 99m Tc-3PRGD 2 exhibited a rapid clearance from the blood with less than 45% of the initial dosage at 10 min after injection and gradual increasing radioactivity in urine with (52.9±6)% of original dose at 1440 min. The whole-body imaging showed high radioactive accumulation in bladder. And the highest 99m Tc-3PRGD 2 uptake was found in the kidneys (3.50×10 −2 mSv/MBq). The 99m Tc-3PRGD 2 exhibited good pharmacokinetic properties and little radiation burden. This study showed that 99m Tc-3PRGD 2 would be a safe and attractive SPECT agent in clinic applications. 99m Tc-3PRGD 2 Integrin α v β 3 Pharmacokinetic Dosimetry References Folkman J . Cancer Med , 2000 , 132 - 52 . Cancer Med Folkman J . Semin Oncol , 2002 , 29 ( 6 Suppl 16 ): 15 - 18 . Semin Oncol Jain R K , Munn L L , Fukumura D . Nat Rev Cancer , 2002 , 2 : 266 - 76 . Nat Rev Cancer Brown E B , Campbell R B , Tsuzuki Y , et al . Nat Med , 2001 , 7 : 864 - 868 . Nat Med Hynes R O . Cell , 1987 , 48 : 549 - 554 . Cell Horton M A . Int J Biochem Cell Biol , 1997 , 29 : 721 - 725 . Int J Biochem Cell Biol Plow E F , Haas T A , Zhang L , et al . J Biol Chem , 2000 , 275 : 21785 - 21788 . J Biol Chem Ruoslahti E , Pierschbacher M D . Sci , 1987 , 238 : 491 - 497 . Sci Haubner R , Weber W A , Beer A J , et al . PLoS Med , 2005 , 2 : e70 . PLoS Med Beer A J , Haubner R , Goebel M , et al . J Nucl Med , 2005 , 46 : 1333 - 1341 . J Nucl Med Indrevoll B , Kindberg G M , Solbackken M , et al . Bioorg Med Chem Lett , 2006 , 16 : 6190 - 6193 . Bioorg Med Chem Lett Beer A J , Haubner R , Sarbia M , et al . Clin Cancer Res , 2006 , 12 : 3942 - 3949 . Clin Cancer Res Kenny L M , Coombes R C , Oulie I , et al . J Nucl Med , 2008 , 49 : 879 - 886 . J Nucl Med Bach-Gansmo T , Danieleeon R , Saracco A , et al . J Nucl Med , 2006 , 47 : 1434 - 1439 . J Nucl Med Axelsson R , Bach-Gansmo T , Castell-Conesa J , et al . Acta Radiol , 2010 , 51 : 40 - 46 . Acta Radiol Wang L , Shi J , Kim Y S , et al . Mol Pharm , 2009, Jan-Fed , 6 : 231 - 245 . Mol Pharm Jia B , Liu Z , Zhu Z , et al . Mol Imaging Biol , 2011 , 13 : 730 - 736 . Mol Imaging Biol Ma Q , Ji B , Jia B , et al . Eur J Nucl Med Mol Imaging , 2011 , 38 : 2145 - 2152 . Eur J Nucl Med Mol Imaging Zhu Z , Miao W , Li Q , et al . J Nucl Med , 2012 , 53 : 1 - 7 . J Nucl Med International commission on radiological protection . Recommendations of the international commission on radiological protection. Publication 60 . Oxford, England : Pergamon Press , 1991 . Recommendations of the international commission on radiological protection. Publication 60 Zhou Y , Kim Y S , Chakraborty S , et al . Mol Imaging , 2011 , 10 : 386 - 397 . Mol Imaging Shi J , Wang L , Kim Y S , et al . J Med Chem , 2008 , 51 : 7980 - 7990 . J Med Chem International commission on radiological protection . Radiation protection in medicine . ICRP publication 105. Ann ICRP 2007 , 37 : 1 - 63 . Radiation protection in medicine International commission on radiological protection . The 2007 recommendations of the international commission on radiological protection . ICRP publication 103. Ann ICRP 2007 , 37 : 1 - 332 . The 2007 recommendations of the international commission on radiological protection Kubo A , Nakamura K , Sanmiya T , et al . Kaku lgaku , 1991 , 28 : 1133 - 1142 . Kaku lgaku 10.13538/j.1001-8042/nst.23.349-354 Supported by the National Natural Science Foundation of China (NSFC) projects (no.81271606) and the Research Fund of Science and Technology Department of Jilin Province (no. 201015185 and no. 201201041) and the Research Fund of Shenzhen Sci-tech Department of Guangdong Province (no.201102154) . 2012-06-05 2012-12-20 2021-01-19 2012 Nuclear Science and Techniques 06 23