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

Department of Radiology, Microbiology, Immunology and Biomedical Engineering University of Miami, School of Medicine, Miami, Florida

Correspondence: For correspondence or reprints contact: Mrinal K. Dewanjee, PhD, University of Miami, School of Medicine, Department of Radiology, Division of Nuclear Medicine (D-57), JMH Central C266—P.O. Box 016960, Miami, FL 33101.

ABSTRACT

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 10⁶ 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.

Key Words: antisense radiopharmaceuticals • indium-111-antisense c-myc probe

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