Tumor Pretargeting in Mice Using 99mTc-Labeled Morpholino, a DNA Analog

Journal of Nuclear Medicine

Mary Rusckowski¹  Suresh Gupta¹  Ning Liu¹  Donald J. Hnatowich¹  Guozheng Liu¹  Kennedy Mang’era¹ 

关键词: antibody;    pretargeting;    ^99mTc;    oligomer;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Over the past several years, investigators in this laboratory and elsewhere have been studying tumor localization by pretargeting with streptavidin and biotin or with avidin and biotin. Despite encouraging results, difficulties related to endogenous biotin and the immunogenicities of streptavidin and avidin have made a search for alternative strategies sensible. Recently, we have considered the use of DNAs and peptide nucleic acids for this purpose because oligomers can have hybridization affinities equivalent to that of biotin for streptavidin or avidin without the associated difficulties. We now report on the use of a morpholino (MORF), another commercially available synthetic oligomer, for pretargeting applications. MORFs support the nitrogenous bases by nonionic phosphorodiamidate linkages and, besides being nuclease resistant, can display good water solubility. Methods: An 18mer MORF and its 18mer complementary MORF (cMORF) were obtained with a primary amine through a 3-member alkyl linker on the 3′ equivalent end. An anti–carcinoembryonic antigen IgG antibody (MN14) was conjugated with MORF, whereas cMORF was conjugated with N-hydroxysuccinimide-mercaptoacetyltriglycine (MAG3) to permit radiolabeling with 99mTc. The biodistribution of labeled cMORF was first evaluated in normal CD-1 mice. Subsequently, nude mice bearing LS174T tumors received 50 μg conjugated antibody 48 h before the administration of 1.0 μg (7.4 MBq) 99mTc-MAG3-cMORF. Control animals received the labeled cMORF without prior administration of the antibody. A clearing step was not used. Results: Biodistributions in normal mice showed that 99mTc-MAG3-cMORF was excreted rapidly through the kidneys, with only 7 percentage injected dose (%ID) remaining within the whole body (excluding urine) at 3 h. In tumor-bearing mice at 24 h, only 11 %ID of the radioactivity remained in the whole body of study animals, and of this amount, 2 %ID/g was in tumor tissue. The sites with the highest %ID were the kidneys, at 4 %ID/g, and the blood, at 0.5 %ID/g; all other organs had <1 %ID/g. At the same time, values for the control animals were 5 %ID (whole body), 0.05 %ID/g (tumor), and 3 %ID (kidneys). All images reflected high uptake in the tumors and low uptake in the normal tissues of the study mice. Conclusion: Pretargeting using MORFs was effective in a mouse tumor model.

【 授权许可】

Unknown