title: Radiation Dosimetry Study of [(89)Zr]rituximab Tracer for Clinical Translation of B cell NHL Imaging using Positron Emission Tomography.
abstract: OBJECTIVE
  We evaluated the dosimetry of [(89)Zr]rituximab, an anti-CD20 immunoPET tracer to image B cell non-Hodgkin's lymphoma (NHL) using a humanized transgenic mouse model that expresses human CD20 transgenic mice (huCD20TM).
  
  
  METHODS
  Rituximab was conjugated to desferrioxamine (Df) for radiolabeling of Zirconium-89. [(89)Zr]rituximab (2.8 ± 0.2 MBq) was tail vein-injected into huCD20T mice. Positron emission tomography (PET)/CT imaging was performed on the two groups of mice (blocking = 2 mg/kg pre-dose of rituximab and non-blocking; n = 5) at eight time points (1, 4, 24, 48, 72, 96, 120, and 168 h) post injection.
  
  
  RESULTS
  The novel [(89)Zr]rituximab PET tracer had good immunoreactivity, was stable in human serum, and was able to specifically target human CD20 in mice. The human equivalents of highest dose (mean ± SD) organs with and without pre-dose are liver (345 ± 284 μSv/MBq) and spleen (1165 ± 149 μSv/MBq), respectively.
  
  
  CONCLUSIONS
  Dosimetry of the human patient whole-body dose was found to be 145 MBq per annum, and the patient dose-limiting organ will be the liver (with rituximab pre-dose blocking) and spleen for non-blocking. The [(89)Zr]rituximab (t½ = 78.4 h) imaging of B cell NHL patients could permit the observation of targeting lesions in NHL patients over an extended period due to longer half-life as compared to the [(64)Cu] rituximab (t½ = 12.7 h).
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), James H. Clark Center, 318 Campus Drive, E153, Stanford, CA, 94305, USA.
authors.forename: Arutselvan
authors.initials: A
authors.lastname: Natarajan
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D016393:Lymphoma, B-Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000032:analysis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011874:Radiometry; D000069283:Rituximab / Q000627:therapeutic use*; D015040:Zirconium / Q000032:analysis* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011868:Radioisotopes; D000069283:Rituximab; D015040:Zirconium