کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2154723 | 1090249 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Dose-dependent effects of (anti)folate preinjection on 99mTc-radiofolate uptake in tumors and kidneys Dose-dependent effects of (anti)folate preinjection on 99mTc-radiofolate uptake in tumors and kidneys](/preview/png/2154723.png)
IntroductionThe folate receptor (FR) is frequently overexpressed in tumors and can be targeted with folate-based (radio)pharmaceuticals. However, significant accumulation of radiofolates in FR-positive kidneys represents a drawback. We have shown that preadministration of the antifolate pemetrexed (PMX) significantly improved the tumor-to-kidney ratio of radiofolates in mice. The aim of this study was to investigate the dose dependence of these effects and whether the same results could be achieved with folic acid (FA) or 5-methyl-tetrahydrofolate (5-Me-THF).MethodsBiodistribution was assessed 4 h postinjection of the organometallic 99mTc-picolylamine monoacetic acid folate in nude mice bearing FR-positive KB tumor xenografts. PMX (50–400 μg/mouse) was injected 1 h previous to radioactivity. The effects of FA and 5-Me-THF (0.5–50 μg/mouse) were investigated likewise. Tissues and organs were collected and counted for radioactivity and the values tabulated as percentage of injected dose per gram tissue (% ID/g).ResultsPMX administration reduced renal retention (<1.6% ID/g vs. control: >10% ID/g), while the tumor uptake (average 1.35%±0.40% ID/g vs. control: 1.79%±0.49% ID/g) was only slightly affected independent of the PMX dose. Replacement of PMX by FA or 5-Me-THF (50 μg/mouse) resulted in a significant renal blockade (<0.1% ID/g) but at the same time in an undesired reduction of tumor uptake (<0.2% ID/g).ConclusionsSelective reduction of radiofolate uptake in kidneys under retention of high tumor accumulation could be achieved in combination with PMX over a broad dose range but not with FA or 5-Me-THF.
Journal: Nuclear Medicine and Biology - Volume 34, Issue 6, August 2007, Pages 603–608