Noninvasive Imaging of c-myc Oncogene Messenger RNA with Indium-111-Antisense Probes in a Mammary Tumor-Bearing Mouse Model

The c-myc oncogene is amplified in leukemia and solid tumors, thus making the c-myc messenger RNA (mRNA) a suitable target for following the progression of malignancy by noninvasive imaging with radiolabeled antisense pharmaceuticals or radiolabeled antisense oligodeoxynucleotide (RASON) probes. Con...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of nuclear medicine (1978) Vol. 35; no. 6; pp. 1054 - 1063
Main Authors:	Dewanjee, Mrinal K, Ghafouripour, Abdol K, Kapadvanjwala, Mansoor, Dewanjee, Sumik, Serafini, Aldo N, Lopez, Diana M, Sfakianakis, George N
Format:	Journal Article
Language:	English
Published:	United States Soc Nuclear Med 01-06-1994
Subjects:	Animals Genes, myc - genetics Indium Radioisotopes - pharmacokinetics Mammary Neoplasms, Experimental - diagnostic imaging Mammary Neoplasms, Experimental - genetics Mice Mice, Inbred BALB C Oligonucleotides, Antisense - pharmacokinetics Radionuclide Imaging RNA, Messenger - analysis RNA, Neoplasm - analysis Tissue Distribution
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The c-myc oncogene is amplified in leukemia and solid tumors, thus making the c-myc messenger RNA (mRNA) a suitable target for following the progression of malignancy by noninvasive imaging with radiolabeled antisense pharmaceuticals or radiolabeled antisense oligodeoxynucleotide (RASON) probes. Considering the higher stability of phosphorothioate over phosphodiester, the probe stability and tumor localization was compared with both derivatives. The 15-mer oligonucleotide sequence was synthesized, aminolinked [sense and antisense phosphodiester (O) and monothioester (S)] and coupled with diethylenetriamine pentaacetate (DTPA)-isothiocyanate and aliquots were lyophilized to make a DTPAAHON kit. The radionuclide 111In was chelated to DTPAAHON derivatives, and free 111In was separated by gel filtration. The radiolabeled antisense and sense probes were injected intravenously in mammary tumor-bearing BALB/c mice (1 x 10(6) cells, 8 days postinoculation). The highest uptake was observed at 2 hr with both thio and oxo derivatives of RASON probes, and small tumors could be imaged noninvasively. Tumor uptake and tumor/blood and tumor/muscle ratios for the sense probe (control) were significantly lower (p < 0.001) than those of the antisense probe. The radiolabeled antisense probe may provide a new sensitive tool for noninvasive imaging of c-myc oncogene mRNA for a variety of malignant tumors at an earlier stage.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0161-5505 1535-5667