Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis

Balloon catheters filled with liquid radioisotopes provide excellent dose h omogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled b alloons may be improved once positron emitters with half-lives below 2 h ar e used instead of the high-energy p-emitters Ho-166, Re-186, or Re-188, all of which have a longer half-life of at least 17 h. Methods: To support thi s concept, the suitability of F-18 (half-life, 109.8 min), Ga-68 (half-life , 67.6 min), C-11 (half-life, 20.4 min), N-13 (half-life, 9.97 min), and O- 15 (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a serie s of phantom experiments using Gafchromic film. Anti proliferative efficacy of positrons emitted by Ga-68 was investigated in vitro using cultured bov ine aortic smooth muscle cells (BASMCs), and was compared with gamma -radia tion emitted by Cs-137. To characterize the remaining risk, we estimated ra diotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with R e-188. Results: Half-dose depth of tissue penetration measured in phantom e xperiments was 0.29 mm for F-18, 0.42 mm for C-11, 0.54 mm for N-13, 0.79 m m for O-15, and 0.9 mm for Ga-68. Irradiation of cultured BASMCs with posit ron radiation (Ga-68) induced dose-dependent inhibition of proliferation wi th complete proliferative arrest at doses exceeding 6 Gy. ED50 and ED80 wer e 2.5 +/- 0.4 Gy (mean SID) and 4.4 +/- 0.8 Gy, respectively. Anti prolifer ative efficacy was equal to that of the 662-keV gamma -radiation emitted by Cs-137 (ED50, 3.8 +/- 0.2 Gy; ED80, 8.0 +/- 0.3 Gy). Estimates made for pa tient whole-body and organ doses were generally below 50 mSv/1.85 GBq for a ll investigated positron emitters. The same dose estimates for Re-188 were 6-20 fold higher. Conclusion- Among the studied radioisotopes, Ga-68 is the most attractive source for liquid-filled balloons because of its convenien t half-life, sufficient positron energy (2.92 MeV), documented antiprolifer ative efficacy, and uncomplicated availability from a radioisotope generato r. The safety profile for Ga-68 is significantly better than that of Re-188 , which suggests this radioisotope should be evaluated further in preclinic al studies.