Feasibility study and dosimetric assessment of radiolabeled drugs injected to the coronary arterial wall to prevent restenosis.
OBJECTIVE
Intramural delivery of a P-32 radiolabeled oligonucleotide (ODN) using an infiltrating catheter has been proposed recently to potentially reduce restenosis in coronary arteries and tested on a limited number of human subjects. However, because of the low efficiency of drug retention (approximately 2-5%) after the initial washout period from this technique, the dose levels to nontarget organs may be significant and thus may require a detailed investigation. The radiation dose distributions resulting from this technique is investigated using the MIRD formalism and Monte Carlo calculations.


METHODS
The total activity of the P-32 ODN to be injected during treatment to deliver a therapeutic dose of approximately 30 Gy to the arterial wall is estimated taking into account the drug delivery efficacy of the infiltrating device (approximately 2-5% typical). Using pharmacokinetic data for P-32 ODN, we estimate the dose to healthy organs resulting from the systemic fraction that is released into the circulatory system during washout (>95% typical). Variabilities in the biological parameters are also identified as important sources of error in the prescribed dose.


RESULTS
A limitation to this technique is the poor accuracy in delivering the prescribed dose due to variability in the amount of drug delivered. Dose to organs is also an important limitation. For example, our calculation indicate that approximately 37 MBq (1 mCi) of P-32 labeled ODN are needed to deliver 30 Gy to the arterial wall assuming a delivery efficiency of 2-5% and a 24-h residence time. This may result in doses of approximately 1 Gy to the spleen and 0.2-0.4 Gy to the liver, kidneys and lungs (95% confidence interval).


CONCLUSIONS
This novel therapy suffers from serious limitations. It is doubtful that a therapeutic dose can be delivered accurately, safely and effectively to the arterial wall because of the poor delivery efficacy and extreme variability found in drug delivery experiments. Also, dose levels to healthy organs appears to be too high to recommend the use of this technique in human experiments.
Department of Medical Physics, McGill University Health Center, Montreal General Hospital, 1650 Avenue Cedar, PQ, H3G 1A4, Montreal, Canada. cjanicki@medphys.mcgill.ca
Christian
C
Janicki
D001918:Brachytherapy / Q000379:methods*; D023903:Coronary Restenosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000378:metabolism*; D005240:Feasibility Studies; D006801:Humans; D007261:Infusions, Intra-Arterial; D008962:Models, Theoretical; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010761:Phosphorus Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011874:Radiometry; D014018:Tissue Distribution
D009841:Oligonucleotides; D010761:Phosphorus Radioisotopes