title: Tumor dosimetry using [124I]m-iodobenzylguanidine microPET/CT for [131I]m-iodobenzylguanidine treatment of neuroblastoma in a murine xenograft model.
abstract: OBJECTIVE
  [(124)I]m-iodobenzylguanidine ((124)I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [(131)I]m-iodobenzylguanidine ((131)I-mIBG) targeted radionuclide therapy of neuroblastoma. (124)I (T (1/2) = 4.2 days) has a comparable half-life to that of (131)I (T (1/2) = 8.02 days) and can be imaged by positron emission tomography (PET) for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from (131)I-mIBG therapy using (124)I-mIBG microPET/CT imaging data in a murine xenograft model of neuroblastoma transduced to express high levels of the human norepinephrine transporter (hNET).
  
  
  METHODS
  In order to enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691) human neuroblastoma cells were engineered to express high levels of hNET protein by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were implanted subcutaneously and into renal capsules in athymic mice. (124)I-mIBG (4.2-6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95 h (0.5, 3-5, 24, 48, and 93-95 h median time points). In vivo biodistribution data in normal organs, tumors, and whole-body were collected from reconstructed PET images corrected for photon attenuation using the CT-based attenuation map. Organ and tumor dosimetry were determined for (124)I-mIBG. Dose estimates for (131)I-mIBG were made, assuming the same in vivo biodistribution as (124)I-mIBG.
  
  
  RESULTS
  All NB1691-hNET tumors had significant uptake and retention of (124)I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. (124)I-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with (131)I-mIBG therapy. For example, in our model system, we estimated that the administration of (131)I-mIBG in the range of 52.8-206 MBq would deliver 20 Gy to tumors.
  
  
  CONCLUSIONS
  The overexpression of hNET was found to be critical for (124)I-mIBG uptake and retention in vivo. The quantitative (124)I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with (131)I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of (131)I-mIBG therapy in human subjects using (124)I-mIBG pretherapy PET/CT data.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA. youngho.seo@ucsf.edu
authors.forename: Youngho
authors.initials: Y
authors.lastname: Seo
authors.forename: W Clay
authors.initials: WC
authors.lastname: Gustafson
authors.forename: Shorouk F
authors.initials: SF
authors.lastname: Dannoon
authors.forename: Erin A
authors.initials: EA
authors.lastname: Nekritz
authors.forename: Chang-Lae
authors.initials: CL
authors.lastname: Lee
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Murphy
authors.forename: Henry F
authors.initials: HF
authors.lastname: VanBrocklin
authors.forename: Miguel
authors.initials: M
authors.lastname: Hernandez-Pampaloni
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Haas-Kogan
authors.forename: William A
authors.initials: WA
authors.lastname: Weiss
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D021621:Imaging, Three-Dimensional; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays
chemical_list: D007457:Iodine Radioisotopes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019797:3-Iodobenzylguanidine