AMPLIFYING TC99M IN TUMOR USING PNA POLYMERS

肿瘤放射性靶向治疗的研究进展 诊断和治疗虽然在总体上是成功的，但仍需要 进步。提供了非常显著改进的潜力 通过放大策略。我们试图在肿瘤部位建立一个 PNAS的复合体可能会吸引极高水平的 正常组织中含量最低的放射性物质。在过去的时间里 几年来，我们开发了一种方法将MAG3偶联到胺- 用于99mTc标记的衍生化低聚物。我们确定两个人 单链磷酸二酯和硫代硫代DNA可能是 然而，不适合，我们确定PNA适合在 活体应用等。最后，我们确定了一个平台(PA) 哪种多价PNA聚合物可以被构建，哪种似乎 具有适合放大的药代动力学特性。vbl.使用 99mTC-PNA和PNA-PA聚合物的初步研究值得注意 用扩增因子获得了阳性的体外结果 超过50个(一个阶段)和2000个(两个阶段)。到目前为止，在体内 研究只在老鼠珠模型中进行，但使用了 一个阶段的放大系数约为50，证明了- 原则性的。有了资金，我们将改善PA作为平台的地位， 测量杂交的亲和力和空间位阻 重新研究其在小鼠体内的药代动力学。此后，这项研究将 重点放在荷瘤小鼠模型的扩增上。我们相信我们的 初步结果很有希望，足以证明有必要做出重大努力 此时要发展放大。观察到的扩增 体外因子为50-2000，特别是扩增因子 在活体内，满足了这种方法的许多明显的担忧，并 证明它应该是可行的。

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.