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, Volume 22, Issue 6, pp 335–346 | Cite as

Die intravasale Strahlenbehandlung zur kombinierten Therapie und Prävention der Restenosierung

Eine Übersicht
  • D. Baumgart
  • U. Quast
  • R. Erbel
Interventionelle Kardiologie 1997—Perspektiven für die Zukunft

Zusammenfassung

Das größte Problem der interventionellen Therapie liegt trotz signifikanter Verbesserungen der Kathetertechnik nach wie vor im Auftreten von Restenosen. Die Implantation von Gefäßstützen, die dem elastischen Kollaps des Gefäßes entgegenwirken, hat zwar zu einer signifikanten Reduktion der Zahl der Restenosen geführt. Die Intimaproliferation als zweiter wichtiger Pathomechanismus der Restenose konnte aber trotz umfangreicher Versuche bisher nicht erfolgreich verhindert werden.

Die Intimaproliferation entsteht als Reaktion auf die Gefäßverletzung nach interventionellen Maßnahmen, zum Beispiel einer Ballondilatation, indem Mono- und Lymphozyten das Einsprossen von Myofibroblasten katalysieren. Hier soll die intrakoronare Bestrahlungstherapie durch Zerstörung der DNA die Zellproliferation der Myofibroblasten hemmen. Dabei ist die antiproliferative Wirkung von der Strahlendosis, dem Bestrahlungszeitpunkt und der Zellzyklusphase abhängig.

Zur intrakoronaren Strahlentherapie stehen β- und γ-Strahlen zur Verfügung. β-Strahler zeichnen sich durch einen starken Dosisabfall wenige Millimeter von der Strahlenquelle entfernt aus. Dadurch werden das umliegende Gewebe wie auch das Katheterpersonal nur einer geringen Strahlendosis ausgesetzt. Durch eine hohe Strahlenintensität beträgt die Behandlungsdauer nur wenige Minuten. Im Gegensatz dazu haben γ-Strahler eine erhöhte Tiefenwirkung mit entsprechender Strahlenbelastung für die Umgebung. Um eine ausreichend hohe Dosis im Zielgewebe zu erreichen, sind mehr als 20 Minuten Bestrahlung notwendig.

Derzeit stehen kathetergestützte Verfahren sowie radioaktive Stents zur Behandlung zur Verfügung. Kathetergestützte Verfahren sind insgesamt flexibler in der Anwendung. Sie erfordern jedoch einen hohen apparativen Aufwand. Stents haben ein inhomogenes Strahlenprofil und können nicht an jeder Stelle des Koronarbaums implantiert werden. Externe Bestrahlungsformen werden aufgrund der mangelnden Wirksamkeit und der hohen Nebenwirkungsraten nicht empfohlen.

Im Tierexperiment hat sich das Schwein als bestes Restenosemodell für den Vergleich zum Menschen erwiesen. Hier konnten intrakoronare β- und γ-Bestrahlungen mit 3 bis 56 Gy eine effektive Reduktion der Intimaproliferation bewirken.

Bisher liegen nur wenige Untersuchungen am Menschen vor. Diese Untersuchungen an kleinen Kollektiven berichten zum großen Teil über eine deutliche Reduktion der Restenosen nach sechs Monaten. Langzeitergebnisse der intrakoronaren Bestrahlung liegen bisher nicht vor. Hier könnten fibrotische Prozesse, die je nach Dosis mit einer Latenz von fünf bis zehn Jahren auftreten können, die initialen Erfolge schmälern. Die intrakoronare Strahlentherapie ist eine vielversprechende Methode zur Prävention der Restenose. Die Dosisfindung im Sinne einer Dosis-Wirkungs-Beziehung, die Festlegung des therapeutischen Fensters und der Zeitpunkt der Bestrahlung sind in der klinischen Anwendung noch nicht ausreichend definiert. Dennoch ist die Strahlentherapie das derzeit hoffnungsvollste Konzept im Kampf gegen die Restenose.

Schlüsselwörter

Intrakoronare Bestrahlung Interventionelle Therapie β-Strahler γ-Strahler Stents Dosis-Wirkungs-Beziehung 

Intravascular irradiation for combined treatment and prevention of restenosis

Summary

Despite numerous efforts in catheter technology and procedural approaches the problem of restenosis in interventional cardiology persists. Although the implantation of coronary stents has significantly reduced restenosis rates based on the inhibition of elastic recoil, intimal proliferation as the second major mechanism for postinterventional restenosis could not effectively be suppressed.

Intimal proliferation is the response to vessel injury following interventional procedure, e. g. balloon angioplasty. It results in the adhesion of mono- and lymphocytes which themselves trigger the colonisation of myofibroblasts. Intracoronary irradiation seeks to prevent this proliferative process as it destroys or irreversibly alters DNA structures of cells at the site of balloon injury. The antiproliferative effect depends on the irradiation dosis, the timing and the cell cycle phase.

Mainly β- and γ-radiation is used for intracoronary irradiation. β-emitters are characterized by a sharp decline of dose rate within millimeters from the actual source. The exposure to surrounding tissue as well the catheter staff can be kept to a minimum. The high intensity of β-emitters allow a short treatment period of minutes to gain an effective radiation dose to the target. In contrast, γ-emitters have a low radial dose distribution resulting in high dosage even centimeters away from the source. These emitters require additional shielding in the catheter laboratory and lead to excessive whole body doses. To achieve a sufficient dose in the target tissue, irradiation times of more than 20 minutes are necessary which prolongs the interventional procedure substantially.

At present, catheter based systems or radioactive implantable stents are available to deliver the required dose. Catheter based systems seem more flexible in a number of considerations. On the other hand they require a substantial amount of hardware. β-emitting stents are implanted via a conventional stent delivery system with small shielding modifications. However, stents emit an inhomogeneous radiation profile due to the mesh-like structure. In addition, not every lesion can be reached by a stent nor does every lesion require a stent solely to deliver radiation. External irradiation is presently not recommended due to its ineffectiveness and the high rate of side effects.

In the experimental setting the porcine model comes closest to the clinical situation in man. Animal experiments have demonstrated the effective reduction of intimal proliferation using β- and γ-sources in a wide dose range of 3 to 56 Gy. Although the initial and early results are convincing little is know about the long term results.

Only few studies have been and are currently performed in patients. Some of these investigations demonstrate a significant reduction of restenosis rate after 6 months. Again, information on long-term results are lacking. It has to be considered that perivascular fibrosis, which may occur with a delay of 5 to 10 years depending on the dosage, could curtail the intial success. Intracoronary irradiation is a promising method for the prevention of restenosis. The dose finding with respect to the dose effect relation, the determination of the therapeutic window and the timing of irradiation have to be further defined in the clinical setting. Nevertheless, intracoronary irradiation remains high on the priority list in fighting restenosis.

Key Words

Intracoronary irradiation Interventional therapy β-emitters γ-emitters Stents Dosis/effect relation 

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Copyright information

© Urban & Vogel 1997

Authors and Affiliations

  1. 1.Klinik für KardiologieZentrum für Innere MedizinEssen
  2. 2.Klinische Strahlenphysik, Abteilung für Strahlentherapie, Radiologisches ZentrumUniversität-GHS EssenEssenDeutschland

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