Successful radiotherapy of tumor in pretargeted mice by 188Re-radiolabeled phosphorodiamidate morpholino oligomer, a synthetic DNA analogue
Authors
Liu, GuozhengDou, Shuping
Mardirossian, George
He, Jiang
Zhang, Surong
Liu, Xinrong
Rusckowski, Mary
Hnatowich, Donald J.
Document Type
Journal ArticlePublication Date
2006-08-18Keywords
AnimalsCarcinoembryonic Antigen
Drug Delivery Systems
Immunoconjugates
Immunoglobulin G
Mice
Mice, Nude
Morpholines
Neoplasms, Experimental
Oligonucleotides
Radioisotopes
Rhenium
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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-06-0844Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41789PubMed ID
16914585Related Resources
ae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-06-0844