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    Successful radiotherapy of tumor in pretargeted mice by 188Re-radiolabeled phosphorodiamidate morpholino oligomer, a synthetic DNA analogue

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    Authors
    Liu, Guozheng
    Dou, Shuping
    Mardirossian, George
    He, Jiang
    Zhang, Surong
    Liu, Xinrong
    Rusckowski, Mary
    Hnatowich, Donald J.
    UMass Chan Affiliations
    Department of Radiology
    Division of Nuclear Medicine
    Document Type
    Journal Article
    Publication Date
    2006-08-18
    Keywords
    Animals
    Carcinoembryonic Antigen
    Drug Delivery Systems
    Immunoconjugates
    Immunoglobulin G
    Mice
    Mice, Nude
    Morpholines
    Neoplasms, Experimental
    Oligonucleotides
    Radioisotopes
    Rhenium
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1587615/
    Abstract
    PURPOSE: Pretargeting has been attracting increasing attention as a drug delivery approach. We recently proposed Watson-Crick pairing of phosphorodiamidate morpholino oligomers (MORF) for the recognition system in tumor pretargeting. MORF pretargeting involves the initial i.v. injection of a MORF-conjugated antitumor antibody and the subsequent i.v. injection of the radiolabeled complement. Our laboratory has reported on MORF pretargeting for diagnosis using (99m)Tc as radiolabel. We now report on the use of MORF pretargeting for radiotherapy in a mouse tumor model using (188)Re as the therapeutic radiolabel. EXPERIMENTAL DESIGN: An initial tracer study was done to estimate radiation dose, and was followed by the radiotherapy study at 400 muCi per mouse with three control groups (untreated, MORF antibody alone, and (188)Re complementary MORF alone). RESULTS: Tracer study indicated rapid tumor localization of (188)Re and rapid clearance from normal tissues with a tumor area under the curve (AUC) about four times that of kidney and blood (the normal organs with highest radioactivity). Tumor growth in the study group ceased 1 day after radioactivity injection, whereas tumors continued to grow at the same rate among the three control groups. At sacrifice on day 5, the average net tumor weight in the study group was significantly lower at 0.68 +/- 0.29 g compared with the three control groups (1.24 +/- 0.31 g, 1.25 +/- 0.39 g, and 1.35 +/- 0.41 g; Ps < 0.05), confirming the therapeutic benefit observed by tumor size measurement. CONCLUSIONS: MORF pretargeting has now been shown to be a promising approach for tumor radiotherapy as well as diagnosis.
    Source

    Clin Cancer Res. 2006 Aug 15;12(16):4958-64 Link to article on publisher's site

    DOI
    10.1158/1078-0432.CCR-06-0844
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/41789
    PubMed ID
    16914585
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    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.CCR-06-0844
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