Current approaches towards tumor targeting of radioactivity for diagnosis and therapy, while successful in general, are in need of improvement. The potential for very significant improvement is offered by amplification strategies. We seek to construct at the tumor site an complex of PNAs which could attract extremely high levels of radioactivity with minimal levels in normal tissues. Over the past several years, we developed a method to conjugate MAG3 to amine- derivatized oligomers for labeling with 99mTc. We determined that both single-chain phosphodiester and phosphorothioate DNA were probably unsuitable, however, we established that PNAs are suitable for this in vivo applications such. Finally, we identified a platform (PA) upon which polyvalent PNA polymers may be constructed and which appears to possess suitable pharmacokinetic properties for amplification. Using 99mTc-PNA and PNA-PA polymers in preliminary studies, remarkably positive in vitro results have been obtained with amplification factors of more than 50 (one stage) and 2,000 (two stages). Thus far, in vivo studies have only been performed in a mouse bead model but with an amplification factor of about 50 for one stage, demonstrating proof-in- principle. With funding, we will improve upon PA as the platform, measure the affinities and steric hindrances of hybridization and reinvestigate the pharmacokinetics in mice. Thereafter, the study will focus on amplification in a tumor bearing mouse model. We believe our preliminary results are sufficiently promising to justify a major effort at this time to develop amplification. The observed amplification factors of 50-2,000 in vitro and, especially, the amplification factor of 50 in vivo, satisfy many of the obvious concerns of this approach and demonstrate that it should work.