title: The potential of theragnostic ¹²⁴I-8H9 convection-enhanced delivery in diffuse intrinsic pontine glioma.
abstract: BACKGROUND
  Reasons for failure in prior human glioma convection-enhanced delivery (CED) clinical trials remain unclear. Concentration-dependent volume of distribution (Vd) measurement of CED-infused agents in the human brain is challenging and highlights a potential technical shortcoming. Activity of iodine isotope 124 ((124)I ) in tissue can be directly measured in vivo with high resolution via PET. With the potential therapeutic utility of radioimmunotherapy, we postulate (124)I conjugated to the antiglioma monoclonal antibody 8H9 may serve as a "theragnostic" agent delivered via CED to diffuse intrinsic pontine glioma.
  
  
  METHODS
  Fifteen rats underwent CED of 0.1-1.0 mCi of (131)I-8H9 to the pons for toxicity evaluation. Six additional rats underwent CED of 10 µCi of (124)I-8H9 to the pons for dosimetry, with serial microPET performed for 1 week. Two primates underwent CED of gadolinium-albumin and 1.0 mCi of (124)I-8H9 to the pons for safety and dosimetry analysis. Serial postoperative PET, blood, and CSF radioactivity counts were performed.
  
  
  RESULTS
  One rat (1.0 mCi (131)I-8H9 infusion) suffered toxicity necessitating early sacrifice. PET analysis in rats yielded a pontine absorbed dose of 37 Gy/mCi. In primates, no toxicity was observed, and absorbed pontine dose was 3.8 Gy/mCi. Activity decreased 10-fold with 48 h following CED in both animal models. Mean Vd was 0.14 cc(3) (volume of infusion [Vi] to Vd ratio = 14) in the rat and 6.2 cc(3) (Vd/Vi = 9.5) in primate.
  
  
  CONCLUSIONS
  The safety and feasibility of (124)I dosimetry following CED via PET is demonstrated, establishing a preclinical framework for a trial evaluating CED of (124)I-8H9 for diffuse intrinsic pontine glioma.
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Neal
authors: N
authors: Luther
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Zhiping
authors: Z
authors: Zhou
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Pat
authors: P
authors: Zanzonico
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Nai-Kong
authors: NK
authors: Cheung
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: John
authors: J
authors: Humm
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Mark A
authors: MA
authors: Edgar
authors: Department of Neurological Surgery, Weill Medical College of Cornell University, New York, New York (N.L., Z.Z.); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (P.Z., J.H.); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (N.-K.C.); Department of Pathology, Emory University, Atlanta, Georgia (M.A.E.); Department of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (M.M.S.).
authors: Mark M
authors: MM
authors: Souweidane
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D020295:Brain Stem Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D018481:Convection; D005910:Glioma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes; D008252:Macaca fascicularis; D008297:Male; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy; D011874:Radiometry; D051381:Rats
chemical_list: C507846:8H9 monoclonal antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007457:Iodine Radioisotopes
keywords: PET; antibody; brain stem; glioma; interstitial; radioimmunotherapy