The 90-day coronary vascular response to (90)Y-beta particle-emitting stents in the canine model.
OBJECTIVE
Long-term preclinical studies using continuous, low-dose-rate vascular brachytherapy with (32)P beta-emitting stents have yielded largely disappointing results. In contrast, a shorter half-life, higher dose-rate (90)Y beta-emitting stent more closely mimics the delivery dose rate characteristics of clinically effective beta- and gamma-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a (90)Y beta-emitting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation.


METHODS
Seventy-seven (90)Y beta-emitting coronary stents (15 mm BXTM, 3.0- and 3.5-mm diameter) were implanted in 26 normal dogs (20-25 kg) using a randomized, blinded study design. Stent activity included nonradioactive controls (n = 24), 4.5 microCi (n = 15), 8 microCi (n = 12), 16 microCi (n = 18), and 32 microCi (n = 8). Histologic endpoints were assessed at 3 months.


RESULTS
Luminal stenosis and neointimal area were similar in control stents and low-activity (4.5 and 8 microCi) (90)Y stents. Higher activity stents (16 and 32 microCi) were associated with significant adverse effects. Frequent total occlusions (5 of 18 stents, 28%; p = 0.008) and a 40% increase in neointimal area (p = 0.024 vs. control) occurred in the 16 microCi group. Incomplete neointimal healing and a trend for reduced neointimal cell density were evident only in the 16- and 32-microCi group.


CONCLUSIONS
Despite unique characteristics (2.7 day half-life and a higher dose rate) of (90)Y beta-emitting coronary stents, they have an adverse effect on neointimal formation, including frequent total occlusions at high activity levels. Incomplete healing, present 90 days (33 half-lives) after stent placement, indicates prolonged recovery from radiation injury.
Taylor
A J
AJ
Division of Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, DC, USA.
Gorman
P D
PD
Hudak
C
C
Tashko
G
G
Sweet
W
W
Farb
A
A
Virmani
R
R
D000818:Animals; D001918:Brachytherapy / Q000295:instrumentation / Q000379:methods*; D003331:Coronary Vessels / Q000293:injuries / Q000528:radiation effects*; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D004311:Double-Blind Method; D006207:Half-Life; D010761:Phosphorus Radioisotopes / Q000627:therapeutic use; D011897:Random Allocation; D015607:Stents / Q000009:adverse effects; D017539:Tunica Intima / Q000293:injuries / Q000528:radiation effects*; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D010761:Phosphorus Radioisotopes; D015021:Yttrium Radioisotopes