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


METHODS
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.
Liu
Guozheng
G
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Guozheng.liu@umassmed.med
Dou
Shuping
S
Mardirossian
George
G
He
Jiang
J
Zhang
Surong
S
Liu
Xinrong
X
Rusckowski
Mary
M
Hnatowich
Donald J
DJ
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology; D016503:Drug Delivery Systems; D018796:Immunoconjugates / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000008:administration & dosage*; D060172:Morpholinos; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000235:genetics*; D011868:Radioisotopes / Q000008:administration & dosage*; D011877:Radionuclide Imaging; D012211:Rhenium / Q000008:administration & dosage*
D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D007074:Immunoglobulin G; D009025:Morpholines; D060172:Morpholinos; D009841:Oligonucleotides; D011868:Radioisotopes; D012211:Rhenium