Radiolabelled Aptamers for Theranostic Treatment of Cancer.

Umair Khalid,Giovanni Mandarano,Sarah Shigdar,Peter Eu,Chris Vi,Joanna Macdonald,Justin Henri

doi:10.3390/ph12010002

Umair Khalid, Giovanni Mandarano + Show 5 more

Open Access

https://doi.org/10.3390/ph12010002

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Journal: Pharmaceuticals	Publication Date: Dec 24, 2018
Citations: 16	License type: CC BY 4.0

Affiliation: Deakin University, Peter MacCallum Cancer Centre

Abstract

Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity. Recent advances in radiochemistry and the development of nucleic acid based targeting molecules, have led to the development of novel agents for use in cancer diagnostics. Monoclonal antibodies may also be used, however, they have inherent issues, such as toxicity, cost, unspecified binding and their clinical use can be controversial. Aptamers are a class of single-stranded RNA or DNA ligands with high specificity, binding affinity and selectivity for a target, which makes them promising for molecular biomarker imaging. Aptamers are presented as being a superior choice over antibodies because of high binding affinity and pH stability, amongst other factors. A number of aptamers directed to cancer cell markers (breast, lung, colon, glioblastoma, melanoma) have been radiolabelled and characterised to date. Further work is ongoing to develop these for clinical applications.

Highlights

Cancer continues to be a major cause of illness and social and economic burden
While current medical imaging modalities can identify tumour masses, they are unable to detect micrometastases before their angiogenesis stage, due to the minimum number of cells required for detection
positron-emission tomography (PET) molecular imaging has been able to improve detection of malignant cells, the typical use of FDG for pathological cells is non-specific for a disease, as normal tissues can uptake FDG which increases the background signal relative to the tumour

Summary

Introduction

Cancer continues to be a major cause of illness and social and economic burden. The numbers of cases increase yearly due to screening and enhanced detection methods. Deaths arising from cancer are typically due to malignant and metastatic disease. Malignant tumours are capable of invading and spreading to surrounding tissue and to distant body sites, in a process known as metastasis, through the circulatory or lymphatic system, giving rise to secondary tumours [1]. More than 50% of patients will have clinically detectable metastatic disease [2]. Metastatic tumours are largely responsible for cancer mortality, early tumour detection can improve prognosis [3]. Current modalities available for imaging tumour masses includes ultrasound, (X-ray) computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) [4] (Table 1)

Method of Detection

Current Imaging Modalities and the Need for Personalized Imaging

Personalised Imaging Techniques—Monoclonal Antibodies

Personlised Imaging Techniques—Peptides and Peptidomimetics

Personalised Imaging Techniques—Aptamers

Findings

Conclusions