title: Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.
abstract: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h.
  
  
  METHODS
  To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re.
  
  
  RESULTS
  Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher.
  
  
  CONCLUSIONS
  Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.
authors.affiliation: Medical Clinic III, Cardiology, Department of Radiation Oncology, University Hospital Homburg/Saar, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Stoll
authors.forename: G D
authors.initials: GD
authors.lastname: Hutchins
authors.forename: W L
authors.initials: WL
authors.lastname: Winkle
authors.forename: A T
authors.initials: AT
authors.lastname: Nguyen
authors.forename: C R
authors.initials: CR
authors.lastname: Appledorn
authors.forename: I
authors.initials: I
authors.lastname: Janzen
authors.forename: H
authors.initials: H
authors.lastname: Seifert
authors.forename: C
authors.initials: C
authors.lastname: Rübe
authors.forename: H
authors.initials: H
authors.lastname: Schieffer
authors.forename: K L
authors.initials: KL
authors.lastname: March
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D002404:Catheterization / Q000009:adverse effects / Q000379:methods*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004869:Equipment Safety; D005462:Fluorine Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D005710:Gallium Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D006207:Half-Life; D009590:Nitrogen Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D010104:Oxygen Radioisotopes / Q000008:administration & dosage / Q000378:metabolism; D019047:Phantoms, Imaging; D018788:Radioactive Hazard Release; D011868:Radioisotopes / Q000008:administration & dosage / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D005710:Gallium Radioisotopes; D009590:Nitrogen Radioisotopes; D010104:Oxygen Radioisotopes; D011868:Radioisotopes