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Imaging oncogene expression.

Xiaobing Tian¹, Mohan R Aruva, Ponugoti S Rao

¹Department of Biochemistry Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Annals of the New York Academy of Sciences

|January 31, 2004

Summary

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New Tc-99m-peptide-PNA probes show promise for noninvasive scintigraphic imaging of breast cancer gene expression. These probes target oncogene messenger RNAs (mRNAs) in tumors, potentially improving early detection and patient management.

Area of Science:

Molecular Imaging
Oncology
Biotechnology

Background:

Breast cancer remains a significant cause of mortality, with current diagnostic methods like mammography missing up to 40% of early cancers.
Existing diagnostic procedures for breast abnormalities are often invasive and yield a high rate of benign results (approximately 85%).
There is a critical need for noninvasive methods to image specific molecular targets, such as overexpressed oncogene messenger RNAs (mRNAs), in vivo.

Purpose of the Study:

To develop and evaluate novel gamma-emitting Technetium-99m (Tc-99m) labeled peptide-nucleic acid (PNA) probes for scintigraphic imaging of breast cancer.
To investigate the potential of these probes to hybridize with complementary oncogene mRNAs (CCND1 and MYC) in human breast cancer xenografts.
To assess the feasibility of noninvasively imaging oncogene overexpression in tumors using these targeted probes.

Related Experiment Videos

Main Methods:

Synthesis of peptide-PNA chimeras by coupling PNA dodecamers antisense to CCND1 and MYC mRNAs to insulin-like growth factor 1 (IGF1) peptide analogs.
Labeling of a chelating peptide-PNA chimera antisense to MYC mRNA with Tc-99m.
In vivo tissue distribution studies in tumor-bearing models using both antisense and mismatch Tc-99m-labeled probes at 4 and 24 hours post-administration.

Main Results:

The synthesized Tc-99m-peptide-PNA probes were successfully prepared.
Tissue distribution studies showed modest accumulation in the liver and kidneys, with appreciable levels concentrating in tumor tissues.
The probes demonstrated the ability to target tumor tissue, indicating potential for imaging.

Conclusions:

The developed Tc-99m-peptide-PNA probes are capable of targeting breast cancer xenografts and concentrating in tumor tissue.
These findings support the potential of using these probes for noninvasive scintigraphic imaging of oncogene mRNA expression in vivo.
Further testing of these Tc-99m-peptide-PNA probes is warranted to advance their application in breast cancer diagnostics and management.