Local intra-arterial drug delivery for prevention of restenosis: comparison of the efficiency of delivery of different radiopharmaceuticals through a porous catheter.
OBJECTIVE
Several radiopharmaceuticals were administered through a porous balloon catheter to compare the absolute amount deposited and the retention in the vessel wall. The reported efficiency of local drug delivery ranges from 0.001% to 0.1%, with poor retention after 24 hours.


METHODS
An endothelin derivative (n = 6), pertechnetate (n = 6), hexamethylpropylene amineoxime (HMPAO) (n = 5), ethyl cysteinate dimer (ECD) (n = 5), and tin colloid (n = 5) were labeled with 185 MBq/mL 99m-technetium. After balloon denudation of the infrarenal aorta in 27 New Zealand White rabbits, 100 microL of each agent was administered through a porous balloon at a pressure of 4 bar. Dynamic and static whole-body scintigrams were obtained for 24 hours. The infrarenal aorta was excised and the activity calculated in a gamma counter.


RESULTS
Apart from their retention in the region of local administration, the radiopharmaceuticals showed different distribution patterns. The highest regional tracer retention was observed with HMPAO. After administration of HMPAO, a significant difference between regional (vessel wall plus surrounding tissue: 14.5% of injected dose [ID]/24 hours) and local (vessel wall: 1.8% ID/24 hours) delivery was found. In contrast, ECD was eliminated quickly (local retention after 24 hours = 0% ID). The retention efficiencies were HMPAO > endothelin derivative > tin colloid > pertechnetate > ECD.


CONCLUSIONS
The different physicochemical and pharmacokinetic properties of radiopharmaceuticals resulted in different delivery efficiencies after local application.
Tepe
G
G
Research Laboratories of Schering AG, Berlin, Germany. Gunnar.Tepe@med.uni-tuebingen.de
Duda
S H
SH
Kalinowski
M
M
Kamenz
J
J
Brehme
U
U
Hanke
H
H
Claussen
C D
CD
Bares
R
R
Baumbach
A
A
Dinkelborg
L M
LM
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002404:Catheterization; D007269:Injections, Intra-Arterial; D008297:Male; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012008:Recurrence
D019275:Radiopharmaceuticals