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. Considering the higher stability of phosphorothioate over phosphodiester, the probe stability and tumor localization was compared with both derivatives.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Dewanjee
M K
MK
Department of Radiology, University of Miami, School of Medicine, Florida 33101.
Ghafouripour
A K
AK
Kapadvanjwala
M
M
Dewanjee
S
S
Serafini
A N
AN
Lopez
D M
DM
Sfakianakis
G N
GN
D000818:Animals; D016259:Genes, myc / Q000235:genetics*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm