Endovascular beta irradiation for prevention of restenosis using solution radioisotopes: pharmacologic and dosimetric properties of rhenium-188 compounds.

Abstract Purpose. Irradiation of the arterial wall with beta particles has been shown to be effective in inhibiting neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA). In this study, we describe the use of 188 W/ 188 Re generators to obtain 188 Re (half-life 16.9 h, maximal beta energy of 2.12 MeV) as a new candidate radioisotope for endovascular irradiation. We have evaluated two [ 188 Re]-compounds as candidates for use as solution-based radiation sources that would allow conventional liquid-filled balloon inflation for delivery of radiation to the vessel wall. While balloon rupture at nominal inflation pressures is a very rare event, ( 188 Re-labeled compounds that are proposed for intravascular therapy. Materials and Methods. Rhenium-188 was obtained as [ 188 Re]-sodium perrhenate by saline elution of an alumina-based 188 W/ 188 Re generator system (>500 mCi). High specific volume solutions of the [ 188 Re]-sodium perrhenate (>50 mCi/ml) were obtained by postelution concentration of the generator bolus by passage through a tandem silver cation/anion column system. Rhenium-188-labeled benzoylthioacetyltriglycine (MAG3) was prepared by stannous ion reduction of [ 188 Re]-perrhenate in the presence of the benzyl-MAG3 substrate, and was characterized as a single radioactive component. Rhenium-188-perrhenate and [ 188 Re]-MAG3 were administered to separate groups of Fischer rats, which were sacrificed at various times and the tissue distribution of 188 Re determined in the major organs. Excretory products were also collected daily from separate groups of rats for each agent over 7 days. The effects of perchlorate and iodide preblocking and postdisplacement of thyroid uptake of [ 188 Re]-perrhenate were also evaluated. Results. Organ uptake values were modest for both agents [ 188 Re after injection of [ 188 Re]-MAG3 was low (0.16 %ID/gram), uptake after injection of [ 188 Re]-perrhenate was higher and could be blocked by pretreatment with perchlorate (intravenous [IV]) or displaced by perchlorate posttreatment. Also, oral or IV iodide pre- or postadministration could also significantly block or displace thyroid uptake of [ 188 Re]-perrhenate. Both [ 188 Re] agents were excreted primarily via the urinary bladder. The excretion half-life of [ 188 Re]-perrhenate was about 7 h; in contrast, the [ 188 Re]-MAG3 complex showed 50% excretion in less than 2 h. The large intestines received the most significant adsorbed dose, with values of 2.0 cGy/mCi for [ 188 Re]-perrhenate and 4.6 × 10 −3 cGy/mCi for [ 188 Re]-MAG3. Conclusions. Rhenium-188-MAG3 shows more rapid urinary bladder excretion in rats than perrhenate and both agents show low organ uptake. Thyroid uptake of free [ 188 Re]-perrhenate can be blocked or displaced with oral perchlorate administration. For the projected use of [ 188 Re]-MAG3 for balloon inflation required for irradiation of the arterial wall, calculated organ dose values are within acceptable limits in the unlikely event of low pressure balloon rupture. Rhenium-188-MAG3 in solution is thus a new candidate for balloon dilation providing uniform endovascular irradiation following PTCA for restenosis therapy. Published by Elsevier Science Inc.