title: Systemic treatment with 4-211Atphenylalanine enhances survival of rats with intracranial glioblastoma.
abstract: OBJECTIVE
  Increased amino acid transport in brain tumours is used for diagnostic purposes. It has been shown that the α-emitting radionuclide astatine-211 labeled to L-phenylalanine is taken up by glioblastoma cells. We here tested, if systemic treatment with 4-[211At]astatine-phenylalanine (At-Phe) has a beneficial effect on survival of rats with intracranial glioblastoma.
  
  
  METHODS
  The rat glioblastoma cell line BT4Ca was implanted into the prefrontal cortex of female BDIX rats by stereotaxic microinjection (10,000 cells/3 µl; n = 83). 3 days after implantation At-Phe or phosphate buffered saline were injected intravenously. A third group was treated twice, i.e., on day 3 and 10. Health condition was assessed each day by using a score system. Rats were sacrificed on days 6, 10, 13 and 17 after implantation, or when showing premortal health condition to measure tumour volume and necrosis. The proliferation index (PI) was assessed after immunohistochemical staining of Ki-67.
  
  
  RESULTS
  Survival time of rats treated twice with At-Phe was significantly prolonged. Additionally, both At-Phe-treated groups remained significantly longer in a better health condition. Rats with poor health status had larger tumours than rats with fair health condition. Overall, irrespective of treatment the PI was reduced in rats with poor health condition. Necrosis was larger in rats treated twice with At-Phe.
  
  
  CONCLUSIONS
  Intravenous treatment with At-Phe enhanced survival time of rats with intracranial glioblastomas and improved health condition. These results encourage studies using local treatment of intracranial glioblastoma with At-Phe, either by repeated local injection or by intracavital application after tumour resection.
authors.forename: N
authors.initials: N
authors.lastname: Borrmann
authors.forename: S
authors.initials: S
authors.lastname: Friedrich
authors.forename: K
authors.initials: K
authors.lastname: Schwabe
authors.forename: H J
authors.initials: HJ
authors.lastname: Hedrich
authors.forename: J K
authors.initials: JK
authors.lastname: Krauss
authors.forename: W H
authors.initials: WH
authors.lastname: Knapp
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: G-J
authors.initials: GJ
authors.lastname: Meyer
authors.affiliation: Dr. Almut Walte, Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1 30625 Hannover, Germany, Tel. +49/(0)511/532 40 11, E-mail: walte.almut@mh-hannover.de.
authors.forename: A
authors.initials: A
authors.lastname: Walte
mesh_terms: D000818:Animals; D001246:Astatine / Q000008:administration & dosage*; D001918:Brachytherapy / Q000379:methods*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy*; D010649:Phenylalanine / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D051381:Rats; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D010649:Phenylalanine; D001246:Astatine
keywords: At-phenylalanine; Glioblastoma; astatine-211; intracranial glioblastoma rat model