90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy

UMMS Affiliation

Department of Radiology, Division of Nuclear Medicine

Publication Date


Document Type



Animals; Heterocyclic Compounds; Mice; Mice, Nude; Morpholinos; Neoplasms; Organometallic Compounds; Radiopharmaceuticals


Cancer Biology | Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Oncology | Radiochemistry | Radiology | Therapeutics


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.

DOI of Published Version



Bioconjug Chem. 2011 Dec 21;22(12):2539-45. doi: 10.1021/bc200366t. Link to article on publisher's site

Journal/Book/Conference Title

Bioconjugate chemistry

Related Resources

Link to Article in PubMed

PubMed ID