title: 90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy.
abstract: While (188)Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the  amine-derivatized cMORF with (90)Y, 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 (90)Y-DOTA-Bn-SCN-cMORF ((90)Y-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 (188)Re. The pharmacokinetics of the (90)Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with (99m)Tc- and (188)Re-MAG(3)-cMORFs. While the (90)Y-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 (90)Y may be comparable to that observed for (188)Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with (90)Y was improved by introducing a prepurification heating step during conjugation. The (90)Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of (188)Re-MAG(3)-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.
authors: Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0243, United States. guozheng.liu@umassmed.edu
authors: Guozheng
authors: G
authors: Liu
authors: Shuping
authors: S
authors: Dou
authors: Yuxia
authors: Y
authors: Liu
authors: Yuzhen
authors: Y
authors: Wang
authors: Mary
authors: M
authors: Rusckowski
authors: Donald J
authors: DJ
authors: Hnatowich
mesh_terms: D000818:Animals; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D060172:Morpholinos / Q000737:chemistry* / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000532:radiotherapy*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D006571:Heterocyclic Compounds; D060172:Morpholinos; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid