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Pretargeting

Morpholinos in pretargeting applications

"Pretargeting" is the use of a Morpholino conjugated to an antibody to bind a particular antigen (e.g. a tumor marker) followed later by a complementary Morpholino conjugated to a radioisotope or other effector molecule. The high molecular mass antibody conjugate clears the blood slowly, but does not damage the body during its residence in the blood. The low molecular mass Morpholino-cargo conjugate binds rapidly with good affinity to the complementary Morpholino on the antigen-bound antibody, but remaining free Morpholino-cargo conjugate clears the blood quickly. If a radio-labeled oligo is used this keeps the radiation dose well below what it would be if a slowly-clearing radio-labeled antibody were used, but provides the binding specificity of an antibody-based targeting method. Non-radioactive cargos can be delivered in enhanced quantity by attaching numerous Morpholino molecules to the pretargeting antibody

References

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Cheng D, Wang Y, Liu X, Pretorius PH, Liang M, Rusckowski M, Hnatowich DJ. Comparison of (18)F PET and (99m)Tc SPECT Imaging in Phantoms and in Tumored Mice. Bioconjug Chem. 2010 Aug 18;21(8):1565-70. doi: 10.1021/bc1001467.

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He J, Liu C, Vanderheyden JL, Liu G, Dou S, Rusckowski M, Hnatowich DJ. Radiolabelling morpholinos with 188Re tricarbonyl provides improved in vitro and in vivo stability to re-oxidation. Nucl Med Commun. 2004 Jul;25(7):731-736.

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Liu G, Zhang S, He J, Zhu Z, Rusckowski M, Hnatowich DJ. Improving the Labeling of S-Acetyl NHS-MAG(3)-Conjugated Morpholino Oligomers. Bioconjug Chem. 2002 Jul 17;13(4):893-897.

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