title: Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin αvβ3-selective radiotracer 99mTc-3PRGD 2 in non-human primates.
abstract: OBJECTIVE
  (99m)Tc-3PRGD(2) is a (99m)Tc-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin α(v)β(3) expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated (99m)Tc-3PRGD(2) in healthy cynomolgus primates for its blood clearance kinetics, biodistribution, and radiation dosimetry.
  
  
  METHODS
  Healthy cynomolgus primates (4.1 ± 0.7 kg, n = 5) were anesthetized, and the venous blood samples were collected via a femoral vein catheter at various time points after injection of ~555 MBq of (99m)Tc-3PRGD(2). Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering ~555 MBq of (99m)Tc-3PRGD(2) in the non-human primates, and the radiation dosimetry estimate was calculated.
  
  
  RESULTS
  (99m)Tc-3PRGD(2) could be easily obtained from freeze-dried kits with high radiochemical purity (>95%) and high specific activity (~5 Ci/μmol). (99m)Tc-3PRGD(2) had a rapid blood clearance with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min postinjection. No adverse reactions were observed up to 4 weeks after the repeated dosing. The whole-body images exhibited high kidney uptake of (99m)Tc-3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of (99m)Tc-3PRGD(2) were found in the kidneys (13.2 ± 1.08 μGy/MBq) and the bladder wall (33.1 ± 1.91 μGy/MBq).
  
  
  CONCLUSIONS
  (99m)Tc-3PRGD(2) can be readily available using the kit formulation. This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of (99m)Tc-3PRGD(2) for noninvasive imaging of integrin α(v)β(3) in humans are warranted.
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Xiaona
authors.initials: X
authors.lastname: Jin
authors.forename: Huiyun
authors.initials: H
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000042:Absorption; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007700:Kinetics; D008252:Macaca fascicularis / Q000097:blood*; D051379:Mice; D057054:Molecular Imaging; D015609:Organotechnetium Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D055503:Protein Multimerization; D011874:Radiometry / Q000379:methods*; D011933:Reagent Kits, Diagnostic; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D039302:Integrin alphaVbeta3; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D011933:Reagent Kits, Diagnostic; C507169:cyclic arginine-glycine-aspartic acid peptide; C561921:technetium 99m (HYNIC-3PRGD(2))(tricine)(TPPTS)