Aptamer-based technology for radionuclide targeted imaging and therapy: a promising weapon against cancer

ABSTRACT

Introduction

aptamers are short artificial, single-strand oligonucleotide sequences (DNA, RNA or modified RNA), capable of binding to biological molecules with high affinity and specificity. Due to their relatively low cost of production and scarce immunogenicity, many efforts have been made to produce aptamers directed against specific molecular targets, such as receptors or transporters overexpressed by malignancies.

Areas covered

the technological approaches for generating aptamers are reviewed. Furthermore, the applications of radiolabeled aptamers for the in vivo imaging of several oncological biomarkers through single photon emission computed tomography (SPECT) or positron emission tomography (PET), are covered. Lastly, targeted therapy based on the utilization of aptamers labeled with radionuclides emitting beta particles is discussed, with particular emphasis to the oncological perspectives.

Expert opinion

The main limitation of radiolabeled aptamers is represented by their in vivo sensitivity to endogenous nuclease, so that several strategies have been developed to increase the stability of these compounds. Although the applications of aptamers are still in a preliminary and pre-clinical phase, it is reasonable to hypothesize that this technology will play a major role for personalized medicine in the next years.

KEYWORDS:

• Aptamers
• theranostics
• biotechnology
• positron emission tomography
• single photon emission tomography
• targeted therapy

Article highlights

• Aptamers are single-strand oligonucleotide sequences (DNA, RNA, or modified RNA), capable of binding specific molecular targets with high affinity.

• Aptamers are characterized by no significant immunogenicity and relatively low cost of production.

• Aptamers directed towards a multiplicity of tumor-associated molecular targets, such as HER2, EGFR, or nucleolin, can be generated through SELEX technology.

• The main drawback of aptamers is represented by their sensitivity to endogenous nucleases, partially overcome through the introduction of chemically modified aptamers.

• Aptamers can be labeled with radionuclides, directly or through the use of several chelating agents.

• Radiolabeled aptamers, directed towards various oncological targets, have been synthesized with promising results for the imaging with gamma-camera/SPECT or PET/CT technology.

• The labeling of aptamers with radionuclides capable of emitting both positrons and beta particles, such as ⁶⁴Cu, might be exploited for targeting tumor biomarkers both for diagnosis (PET) and treatment (radionuclide therapy) purposes, paving the ground to innovative theranostic approaches.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The paper was not funded.