title: Biodistribution, pharmacokinetics, and nuclear imaging studies of 111In-labeled rGel/BLyS fusion toxin in SCID mice bearing B cell lymphoma.
abstract: OBJECTIVE
  We examined the biodistribution and pharmacokinetics of (111)In-labeled rGel/BLyS, a gelonin toxin (rGel)-B lymphocyte stimulator (BLyS) fusion protein.
  
  
  METHODS
  rGel/BLyS was labeled with In-111 through DTPA with a labeling efficiency >95%. Biodistribution/imaging studies were obtained in severe-combined immunodeficiency mice bearing diffuse large B cell lymphoma OCI-Ly10. Pharmacokinetic studies were performed in BALB/c mice.
  
  
  RESULTS
  In vitro, DTPA-conjugated rGel/BLyS displayed selective cytotoxicity against OCI-Ly10 cells and mantle cell lymphoma JeKo cells. In vivo, rGel/BLyS exhibited a tri-exponential disposition with a rapid initial mean distribution followed by an extensive mean distribution and a long terminal elimination phase. At 48 h after injection, uptake of the radiotracer in tumors was 1.25 %ID/g, with a tumor-to-blood ratio of 13. Tumors were clearly visualized at 24-72 h post-injection. Micro-SPECT-CT images and ex vivo analyses confirmed the accumulation of rGel/BLyS in OCI-Ly10 tumors.
  
  
  CONCLUSIONS
  (111)In-DTPA-rGel/BLyS are distributed to B cell tumors and induce apoptosis in tumors. Preclinical antitumor studies using rGel/BLyS should use a twice-per-week treatment schedule.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wen
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Lyu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenblum
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016923:Cell Death; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D016393:Lymphoma, B-Cell / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D004369:Pentetic Acid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013194:Staining and Labeling; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D053264:B-Cell Activating Factor; D007205:Indium Radioisotopes; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D004369:Pentetic Acid