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Noninvasive imaging of c-myc oncogene messenger RNA with indium-111-antisense probes in a mammary tumor-bearing mouse
M K Dewanjee1, A K Ghafouripour, M Kapadvanjwala
1Department of Radiology, University of Miami, School of Medicine, Florida 33101.
Unlabelled:
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.
Conclusion:
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.
Insights
Radiolabeled antisense probes targeting c-myc messenger RNA (mRNA) enable noninvasive imaging of tumors. Phosphorothioate probes showed improved tumor localization for early malignancy detection.
Area of Science:
- Oncology
- Molecular Imaging
- Biotechnology
Background:
- The c-myc oncogene is frequently amplified in various leukemias and solid tumors.
- c-myc messenger RNA (mRNA) presents a viable target for monitoring malignancy progression.
- Noninvasive imaging using radiolabeled antisense probes offers a promising approach for cancer detection.
Purpose of the Study:
- To evaluate radiolabeled antisense oligodeoxynucleotide (RASON) probes for noninvasive imaging of c-myc mRNA.
- To compare the stability and tumor localization of phosphorothioate versus phosphodiester RASON derivatives.
- To assess the potential of RASON probes for early-stage cancer detection.
Main Methods:
- Synthesis of 15-mer oligonucleotide sequences (sense and antisense) with phosphodiester (oxo) and phosphorothioate (thio) backbones.
- Aminolinking and conjugation with diethylenetriamine pentaacetate (DTPA) to create DTPAAHON kits.
- Chelation of radionuclide 111In to DTPAAHON derivatives and intravenous injection into mammary tumor-bearing mice.
Main Results:
- Both thio and oxo RASON probe derivatives demonstrated high uptake at 2 hours post-injection, enabling noninvasive imaging of small tumors.
- Antisense probes exhibited significantly higher tumor uptake and tumor-to-blood/muscle ratios compared to sense (control) probes (p < 0.001).
- The study confirmed the feasibility of noninvasive imaging of c-myc mRNA in tumors.
Conclusions:
- Radiolabeled antisense probes, particularly phosphorothioate derivatives, are effective for noninvasive imaging of c-myc oncogene mRNA.
- This technology may offer a sensitive new tool for earlier detection of various malignant tumors.
- Further development of RASON probes holds potential for improved cancer diagnostics.