Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10915927 | Nuclear Medicine and Biology | 2015 | 7 Pages |
Abstract
Down-regulating bcl-2, an anti-apoptotic proto-oncogene, is a mechanism to reverse chemotherapy resistance or failure in humans with NHL. We have developed a 177Lu-DOTA-anti-bcl-2-PNA-Tyr3-octreotate conjugate for targeted antisense radiotherapy, in which down-regulation of bcl-2 and delivery of cytotoxic radiation occur simultaneously. Our previous studies have shown highly specific inhibition of bcl-2 protein, additive in vitro cytotoxic effects on human lymphoma cells, and favorable biodistribution and dosimetric properties. Lutetium-177 targeted antisense radiotherapy demonstrates a significant advantage over conventional 177Lu-peptide receptor radionuclide therapy in a mouse model of NHL. Our preclinical studies identified an effective combination of antisense and radionuclide therapy, with the goal of future clinical trials in patients.
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Authors
Dijie Liu, Ethan R. Balkin, Fang Jia, Varyanna C. Ruthengael, C. Jeffrey Smith, Michael R. Lewis,