90Y labeled Phosphorodiamidate Morpholino Oligomer for Pretargeting Radiotherapy

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• 作者：Guozheng Liu ; Shuping Dou ; Yuxia Liu ; Yuzhen Wang ; Mary Rusckowski ; Donald J. Hnatowich
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：December 21, 2011
• 年：2011
• 卷：22
• 期：12
• 页码：2539-2545
• 全文大小：260K
• 年卷期：v.22,no.12(December 21, 2011)
• ISSN：1520-4812

文摘

While ¹⁸⁸Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the amine-derivatized cMORF with ⁹⁰Y, a longer physical half-life nuclide, was not very successful. After developing a method involving a prepurification heating step during conjugation that increases labeling efficiency and label stability, the biodistribution of ⁹⁰Y-DOTA-Bn-SCN-cMORF (⁹⁰Y-DOTA-cMORF) was measured in normal mice and in MORF-CC49 pretargeted mice that bear LS174T tumors. Absorbed radiation doses were then estimated and compared to those estimated for ¹⁸⁸Re. The pharmacokinetics of the ⁹⁰Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with ^99mTc- and ¹⁸⁸Re-MAG₃-cMORFs. While the ⁹⁰Y-DOTA-cMORF cleared rapidly from normal tissues, tumor clearance was very slow and tumor radioactivity accumulation was constant for at least 7 days such that the tumor/blood (T/B) ratio increased linearly from 6 to 25 over this period. Therefore, by extrapolation, normal tissue toxicities following administration of therapeutic doses of ⁹⁰Y may be comparable to that observed for ¹⁸⁸Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with ⁹⁰Y was improved by introducing a prepurification heating step during conjugation. The ⁹⁰Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of ¹⁸⁸Re-MAG₃-cMORF and was retained well in the tumor pretargeted with MORF-CC49. Because of the longer physical half-life, the T/NT absorbed radiation dose ratios were improved in most organs and especially in blood.