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

H. P. Stoll, Gary Hutchins, W. L. Winkle, A. T. Nguyen, C. R. Appledorn, I. Janzen, H. Seifert, C. Rübe, H. Schieffer, K. L. March

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 highenergy β-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 γ-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. ED50 and ED80 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 γ-radiation emitted by 137Cs (ED50, 3.8 ± 0.2 Gy; ED80, 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1375-1383
Number of pages9
JournalJournal of Nuclear Medicine
Volume42
Issue number9
StatePublished - 2001
Externally publishedYes

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Radioisotopes
Half-Life
Radiotherapy
Electrons
Radiation
Smooth Muscle Myocytes
Radionuclide Generators
Rupture
Safety
Isotopes
Catheters

Keywords

  • Brachytherapy
  • Positron emitters
  • Radiation
  • Restenosis

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis. / Stoll, H. P.; Hutchins, Gary; Winkle, W. L.; Nguyen, A. T.; Appledorn, C. R.; Janzen, I.; Seifert, H.; Rübe, C.; Schieffer, H.; March, K. L.

In: Journal of Nuclear Medicine, Vol. 42, No. 9, 2001, p. 1375-1383.

Research output: Contribution to journalArticle

Stoll, HP, Hutchins, G, Winkle, WL, Nguyen, AT, Appledorn, CR, Janzen, I, Seifert, H, Rübe, C, Schieffer, H & March, KL 2001, 'Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis', Journal of Nuclear Medicine, vol. 42, no. 9, pp. 1375-1383.
Stoll, H. P. ; Hutchins, Gary ; Winkle, W. L. ; Nguyen, A. T. ; Appledorn, C. R. ; Janzen, I. ; Seifert, H. ; Rübe, C. ; Schieffer, H. ; March, K. L. / Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis. In: Journal of Nuclear Medicine. 2001 ; Vol. 42, No. 9. pp. 1375-1383.
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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 highenergy β-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 γ-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. ED50 and ED80 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 γ-radiation emitted by 137Cs (ED50, 3.8 ± 0.2 Gy; ED80, 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. Conclusion: 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.",
keywords = "Brachytherapy, Positron emitters, Radiation, Restenosis",
author = "Stoll, {H. P.} and Gary Hutchins and Winkle, {W. L.} and Nguyen, {A. T.} and Appledorn, {C. R.} and I. Janzen and H. Seifert and C. R{\"u}be and H. Schieffer and March, {K. L.}",
year = "2001",
language = "English (US)",
volume = "42",
pages = "1375--1383",
journal = "Journal of Nuclear Medicine",
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TY - JOUR

T1 - Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis

AU - Stoll, H. P.

AU - Hutchins, Gary

AU - Winkle, W. L.

AU - Nguyen, A. T.

AU - Appledorn, C. R.

AU - Janzen, I.

AU - Seifert, H.

AU - Rübe, C.

AU - Schieffer, H.

AU - March, K. L.

PY - 2001

Y1 - 2001

N2 - 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 highenergy β-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 γ-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. ED50 and ED80 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 γ-radiation emitted by 137Cs (ED50, 3.8 ± 0.2 Gy; ED80, 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. Conclusion: 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.

AB - 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 highenergy β-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 γ-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. ED50 and ED80 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 γ-radiation emitted by 137Cs (ED50, 3.8 ± 0.2 Gy; ED80, 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. Conclusion: 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.

KW - Brachytherapy

KW - Positron emitters

KW - Radiation

KW - Restenosis

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