Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+
Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+
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DOI：
10.1016/j.nucmedbio.2004.03.008
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发表时间：
2004-08-01
影响因子：
3.1
通讯作者：
Krenning, EP
中科院分区：
文献类型：
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作者：
Breeman, WAP;De Jong, MTM;Krenning, EP
肽受体靶向放射性核素疗法目前用放射性标记的DOTA缀合肽，如[Y-90-DOTA（O），Tyr（3）]奥曲肽（也称为OctreoTher（R）或Y-90-DOTATOC）进行。Y-90（3+）的掺入通常大于或等于99%，然而，由于患者总剂量可高达26 GBq或700 mCi，游离Y-90（3+）（=未掺入DOTA）的量可能是相当大的。游离Y-90（3+）在骨中积累，结果是不希望的骨髓辐射。Y-90-DTPA通过肾脏快速排泄。将游离Y-90（3+）掺入到90 Y-DTPA中可能会阻止这一部分在骨中蓄积，因此我们研究了（YCl_3）-Y-90、[Y-90-DOTA（0），Tyr（3）]奥曲肽和Y-90-DTPA在大鼠体内的生物分布;在静脉内注射之前，将含有[Y-90-DOTA（0），Tyr（3）]奥曲肽的溶液中的10%游离Y-90（3+）络合到Y-90-DTPA中的可能性;以及在存在和不存在过量DTPA的情况下，在[Y-90-DOTA（0），Tyr（3）]奥曲肽溶液中的10%游离Y-90（3+）对大鼠体内的生物分布的影响。（YCl 3）-Y-90显示高的骨骼摄取（即，1% ID（注射剂量）/g股骨，主要定位于骺板），24 h全身滞留74% ID; 90 Y-DTPA具有快速肾清除，24 h全身滞留
Peptide receptor- targeted radionuclide therapy is nowadays being performed with radiolabeled DOTA-conjugated peptides, such as [Y-90-DOTA(O),Tyr(3)] octreotide (also known as OctreoTher(R) or Y-90-DOTATOC). The incorporation of Y-90(3+) is typically greater than or equal to99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi the amount of free Y-90(3+) (=non-DOTA- incorporated) can be substantial. Free Y-90(3+) accumulates in bone with undesired radiation of bone marrow as a consequence. Y-90-DTPA is excreted rapidly via the kidneys. Incorporation of free Y-90(3+) into 90Y-DTPA might prevent this fraction from being accumulated into bone, therefore we have investigated: the biodistribution in rats of (YCl3)-Y-90,, [Y-90-DOTA(0),Tyr(3)] octreotide, and Y-90-DTPA; possibilities to complex 10% of free Y-90(3+) in a [Y-90-DOTA(0),Tyr(3)]octreotide containing solution into Y-90-DTPA prior to intravenous injection; and effects of 10% free Y-90(3+) in [Y-90-DOTA(0),Tyr(3)]octreotide solution, in the presence and in the absence of excess DTPA, on the biodistribution of in rats. The following results are presented: (YCl3)-Y-90 showed high skeletal uptake (i.e., 1% ID (injected dose) per gram femur, with main localization in the epiphyseal plates) and a 24 h total body retention of 74% ID; 90Y-DTPA had rapid renal clearance, and 24 h total body retention of