? Despite several decades of effort, conventional radioimmunodetection of prostate cancer is still providing marginal results because of the slow pharmacokinetics and localization in normal tissues. ProstaScint is the only FDA approved prostate cancer imaging agent currently available. In addition to the intrinsic problems with conventional radioimmunodetection, it targets an intracellular epitope difficult to be accessed. As such, alternative methods for the sensitive and selective detection of prostate cancers are needed. One of the most attractive alternative approaches to imaging prostate cancer involves pretargeting. On other tumor types, preclinical studies of pretargeting have clearly demonstrated efficacy and early clinical trials are providing encouraging results. This proposal will use an antibody with high affinity against an extracellular and conformational epitope of PSMA, the 3C6, along with a pretargeting strategy in a mouse prostate cancer model. The non-radioactive 3C6 conjugated with a morpholino oligomer (MORF) will be injected and followed at a later time with a low molecular weight radiolabeled complementary morpholino oligomer (cMORF). The antibody 3C6 shows extremely high affinity for the extracellular conformational epitope of PSMA. The radiolabeled cMORF can hybridize with the MORF, clear very rapidly from the normal tissues, and excrete exclusively through the kidneys. An image of diagnostic quality should be obtained very rapidly in contrast to conventional imaging with radiolabeled ProstaScint. This proposed study seeks to show that pretargeting with MORFs along with an extracellular antibody may image prostate cancer in a mouse model more effectively than ProstaScint (as a gold standard). Thus, we intend to optimize conditions of dosage and timing for pretargeted localization of 99mTc-cMORF in mice with prostate xenografts having previously received MORF-conjugated prostate specific antibodies. Application of pretargeting strategy along with an extracellular antibody will translate into a more sensitive imaging method than the conventional ProstaScint. Successful pretargeting with antibody and MORF will demonstrate the advantages over anatomical imaging methods such as Ultrasound, CT, and MRI, so that a more efficient means for early detection of prostate cancer might be possible. Based on our experiences in this pretargeting strategy, we are confident that these investigations on the pretargeting imaging of prostate cancer models with MORFs will be successful. ? ?
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