title: Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma.
abstract: OBJECTIVE
  TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma.
  
  
  METHODS
  Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I.
  
  
  RESULTS
  Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months.
  
  
  CONCLUSIONS
  A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.
authors.affiliation: Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. Adam.Mamelak@cshs.org
authors.forename: Adam N
authors.initials: AN
authors.lastname: Mamelak
authors.forename: Steven
authors.initials: S
authors.lastname: Rosenfeld
authors.forename: Richard
authors.initials: R
authors.lastname: Bucholz
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
authors.forename: L Burt
authors.initials: LB
authors.lastname: Nabors
authors.forename: John B
authors.initials: JB
authors.lastname: Fiveash
authors.forename: Sui
authors.initials: S
authors.lastname: Shen
authors.forename: M B
authors.initials: MB
authors.lastname: Khazaeli
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.forename: Medhat
authors.initials: M
authors.lastname: Osman
authors.forename: Bart
authors.initials: B
authors.lastname: Guthrie
authors.forename: Susan
authors.initials: S
authors.lastname: Schade-Bijur
authors.forename: Diana M
authors.initials: DM
authors.lastname: Hablitz
authors.forename: Vernon L
authors.initials: VL
authors.lastname: Alvarez
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gonda
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects*; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D011859:Radiography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012604:Scorpion Venoms / Q000008:administration & dosage* / Q000009:adverse effects*; D016019:Survival Analysis; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D012604:Scorpion Venoms; C091539:Chlorotoxin