Three-dimensional dose model for the comparison of 177Lu-HuCC49DeltaCH2 and 177Lu-HuCC49 radioimunotherapy in mice bearing intraperitoneal xenografts.
Three-dimensional dose model for the comparison of 177Lu-HuCC49DeltaCH2 and 177Lu-HuCC49 radioimunotherapy in mice bearing intraperitoneal xenografts.
复制标题
用于比较 177Lu-HuCC49DeltaCH2 和 177Lu-HuCC49 放射免疫疗法对腹膜内异种移植小鼠的三维剂量模型。
DOI：
10.1089/108497803765036418
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Buchsbaum,DonaldJ
中科院分区：
文献类型：
--
作者：
Roberson,PeterL;Yokoyama,Shigeru;Rogers,BuckE;Buchsbaum,DonaldJ
Uptake and dose distributions in peritoneal LS174T colon tumor xenografts were compared for a humanized construct of the CC49 (HuCC49) high-affinity anti-TAG-72 monoclonal antibody and a construct with the CH2 region deleted (HuCC49ΔCH2), both labeled with177Lu using a PA-DOTA bifunctional chelating agent and injected in the peritoneum. Tumors were resected and serially sectioned at 1 h, 4 h, 24 h, and 48 h postinjection. Between 5 and 24 (average 16) sections were retained per tumor for autoradiography. The typical section interval was 340 μm and thickness was 16 μm. Tumor sections were air dried and placed on film and/or phosphor screen. Section images were digitized at 100 μm resolution electronically (phosphor screen) or by laser densitometer (film). Section images were used to generate tumor surface descriptions and activity distributions by reconstructing the activity densities in three dimensions. Three-dimensional dose-rate calculations, performed using a point kernel for177Lu, were used to prepare radial histograms describing the variation in dose rate as a function of distance from the tumor center to surface. At early times postinjection, the177Lu-HuCC49ΔCH2 antibody displayed higher dose rates near the tumor surface compared to the177Lu-HuCC49 antibody. At 24 h postinjection, dose rate distributions appeared similar for both antibodies and more uniform than at earlier times. The177Lu-HuCC49ΔCH2 antibody indicated improved uniformity at 48 h postinjection. Cell survival calculations based on the three-dimensional dose rate distributions favored177Lu-HuCC49ΔCH2 for equal injection activities. However the most significant effect was the greater injected dose tolerated for the177Lu-HuCC49ΔCH2 antibody based on equivalent estimated bone marrow dose.
